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Short stature as the primary manifestation of coeliac disease.

Thirty-four patients with short stature of undetermined cause and no gastrointestinal symptoms underwent jejunal biopsy for exclusion of coeliac disease. Eight had subtotal or severe partial villous atrophy and seven showed a significant acceleration in height and weight velocity after the introduction of a gluten-free diet. Short stature by itself, in the complete absence of gastrointestinal symptoms, is an indication for jejunal biopsy, particularly if bone age is delayed by more than 4 years and/or there are associated haematological abnormalities.

Adolescent↗

Aluminosilicates and senile plaque formation in Alzheimer's disease.

Aluminium and silicon were found to be colocalised in the central region of senile plaque cores in studies with energy dispersive X-ray microanalysis. The distribution of these elements was similar in cores isolated from the cerebral cortex of patients with senile dementia of the Alzheimer type and in cores studied in situ from tissue sections from the cerebral cortex of presenile and senile patients with Alzheimer's disease, and elderly, mentally normal patients. High-resolution solid-state nuclear magnetic resonance techniques showed aluminium and silicon to be present as aluminosilicates. The presence of aluminosilicates at the centre of senile plaque cores contrasts with the distribution of other inorganic constituents and suggests that they may be involved in the initiation or early stages of senile plaque formation.

Aged↗

Alzheimer's-disease-like changes in tau protein processing: association with aluminium accumulation in brains of renal dialysis patients.

Tau protein is a major structural protein of the paired helical filaments (PHFs) found in both neuritic senile plaques and neurofibrillary tangles in Alzheimer's disease (AD). Senile plaques also contain amyloid beta protein (A beta). We did an immunochemical analysis of frontal cortex from 15 dialysis cases, 5 Alzheimer's disease patients, and 6 control cases to see whether AD-like changes in A beta deposition and tau protein were linked to aluminium accumulation. Dialysis patients were used because they are frequently exposed to increased levels of aluminium. 8 of the 15 dialysis cases had insoluble A beta, but there was no association between its presence and the accumulation of aluminium. However, we found AD-like changes in the processing of tau protein. In white matter, truncated tau protein in the PHF-core fraction and endogenously truncated tau in the supernatant fraction were both increased in association with aluminium accumulation in the brain. In grey matter, normal tau protein was depleted and insoluble hyperphosphorylated tau increased in association with aluminium concentration. Protease-resistant PHFs were present in grey matter in 2 dialysis cases, a frequency above that expected for AD in this age group. PHF-core tau in both grey and white matter correlated with decreased levels of normal tau protein in white matter. These findings are consistent with a role for aluminium in the development of AD-like pathology in patients subjected to prolonged aluminium exposure.

Adult↗

Randomised investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy.

BACKGROUND: There is accumulating evidence that inflammatory cytokines have an important role in the pathogenesis of heart failure. Plasma concentrations of tumour necrosis factor alpha (TNF-alpha) are high in heart failure and have been correlated with the severity of symptoms. Pentoxifylline suppresses the production of TNF-alpha. This study aimed to assess the effects of pentoxifylline on left-ventricular function and functional class in patients with idiopathic dilated cardiomyopathy. METHODS: We undertook a single-centre, prospective, double-blind, randomised, placebo-controlled trial, in which 28 patients with idiopathic dilated cardiomyopathy were assigned pentoxifylline 400 mg three times daily or matching placebo. Clinical, echocardiographic, and radionuclide assessments were done at baseline and after 6 months of treatment. Primary endpoints were New York Heart Association (NYHA) functional class and left-ventricular function. FINDINGS: Baseline characteristics were similar in the two groups. Four patients died during the study period, all in the placebo group. After 6 months of treatment, the proportion of patients in NYHA functional class I or II was higher in the pentoxifylline group than in the placebo group (14/14 vs 10/14; p=0.01), and ejection fraction was higher in the pentoxifylline group than in the placebo group (mean 38.7% [SD 15.0] vs 26.8% [11.0], p=0.04). At 6 months, TNF-alpha plasma concentrations were significantly lower in the pentoxifylline-treated group than in the placebo group (2.1 [1.0] vs 6.5 [5.0] pg/mL, p=0.001). INTERPRETATION: Our results suggest that pentoxifylline improves symptoms and left-ventricular systolic function in patients with idiopathic dilated cardiomyopathy. These results must be confirmed in larger-scale trials.

Cardiomyopathy, Dilated↗

Modulation of mitomycin C mutagenicity on Saccharomyces cerevisiae by glutathione, cytochrome P-450, and mitochondria interactions.

It is well established that most anticancer drugs also have mutagenic effects and require metabolic activation before exerting their mutagenic/antiblastic activity. Antitumoral compound effects strongly depend on the biochemical/physiological conditions of the tumoral cells, and especially on the activation of specific drugs metabolizing enzymes and on respiration. We examined the mitomycin C-induced mutagenic effects on the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant p degrees at different contents of glutathione and cytochrome P-450, molecules able to activate/detoxicate xenobiotics. The mutagenic activity of the drug was evaluated as frequency of mitotic gene conversion and reversion in different physiological conditions. The highest frequencies of reversion and especially of gene conversion were observed at the highest cytochrome P-450 contents in the D7 strain with a further increase at high glutathione level. In the respiratory-deficient strain, the highest frequency of convertants was shown at low glutathione level and lack of cytochrome P-450. These results suggest the relevance of mitochondrial functionality for the expression of genotoxic activity of this anticancer drug.

Buthionine Sulfoximine↗

Structure and properties of pyruvate decarboxylase and site-directed mutagenesis of the Zymomonas mobilis enzyme.

Pyruvate decarboxylase (EC 4.1.1.1) is a thiamin diphosphate-dependent enzyme that catalyzes the penultimate step in alcohol fermentation. The enzyme is widely distributed in plants and fungi but is rare in prokaryotes and absent in animals. Here we review its structure and properties with particular emphasis on how site-directed mutagenesis of the enzyme from Zymomonas mobilis has assisted us to understand the function of critical residues.

Amino Acid Sequence↗

Influences of The Great Hanshin-Awaji Earthquake on glycemic control in diabetic patients.

We investigated influences on glycemic control in 177 diabetic patients after The Great Hanshin-Awaji Earthquake which occurred on January 17, 1995. Changes in serum HbA(1c) level were studied according to the worsen rate of dietary and living conditions. A significant temporary increase in the mean value of HbA(1c) level was found after the earthquake (8.34 +/- 2.07% in March, 1995 vs. 7.74 +/- 1.82% in December, 1994, P < 0.01). Ninety nine of them showed more than 0.5% in the rate of increase. Multiple regression analysis was applied to the following factors: inappropriate diet, discontinuation of drug uptake, reduction of exercise, destruction of house, long stay at shelter, sex, age, and pre-earthquake therapy. Among them, inappropriate diet demonstrated the highest partial regression coefficient to raise the mean value of the HbA(1c) level. The increased level of HbA(1c) declined gradually to the pre-earthquake level in September, 1995. This study emphasizes the importance of appropriate diet for diabetic patients during a natural disaster. To fulfil it, medical staff have to educate diabetic patients of their disorders tediously in ordinary time. In addition, it seems quite useful to supply a medical information card and a small medical bag containing essential drugs to each patient.

Adult↗

How many insulin-like growth factor binding proteins?

Mac25, connective tissue growth factor, the nov-oncogene and cyr61 have been proposed as insulin-like growth factor binding proteins (IGFBPs) although they bind the ligand with very low affinity. Sequence similarity between the candidate proteins and the recognised IGFBPs is restricted to a single cysteine-rich N-terminal domain. The cysteine-rich domain (CRD) can be found in other vertebrate and invertebrate proteins that are associated with the extracellular matrix but otherwise have vastly different functions. Characteristically, the proteins with the CRD have a modular architecture suggesting that exon shuffling has played a significant role in their evolution. Although the proposed candidate proteins may not be IGFBPs, linkage relationships of the latter suggest that two other IGFBPs may indeed exist.

Amino Acid Sequence↗

Chronic hyperglycaemia increases neuronal sensitivity to high potassium in hippocampal slices from streptozotocin-treated diabetic rats.

The chronic hyperglycaemia associated with diabetes mellitus increases susceptibility to epileptiform-like activity in the central nervous system. Changes in extracellular potassium levels directly influence neuronal excitability and significantly one of the major regulators of extracellular potassium, the Na-K ATPase, is known to be down-regulated by chronic hyperglycaemia. The sensitivity of hippocampal slices, from rats made diabetic for 2-3 weeks with streptozotocin, to increases in the extracellular potassium concentration ([K+]o) was, therefore, investigated. Raising [K+]o to 10 mM increased the number of orthodromically-evoked population spikes (PSs) in area CA1. This recruitment was significantly greater in hippocampal slices from diabetic rats, which also exhibited significantly more spontaneous activity. These findings confirm a diabetes-dependent increase in sensitivity of central neurones to changes in [K+]o and may help to explain the increased susceptibility to epileptiform activity in this disease state.

Animals↗