Methotrexate toxicity complicating a case of rheumatoid arthritis associated Interstitial Lung Disease: Lessons to learn.

Rheumatoid arthritis (RA) is one of the most common types of autoimmune arthritis. It can also involve other organs, including vascular structures, and lungs which are affected in 60% to 80% of cases. Other complications may present as airway infections and drug related pulmonary toxicity. We present the case of 75-year-old male patient of North African decent that was hospitalized initially for chronic dyspnea associated with other systemic manifestations, and in whom we confirmed the diagnosis of Rheumatoid arthritis associated interstitial lung disease. The patient was treated with methotrexate (MTX) and later on, he developed a fatal case of methotrexate related pulmonary toxicity.

Stomatal vs. genome size in angiosperms: the somatic tail wagging the genomic dog?

BACKGROUND AND AIMS: Genome size is a function, and the product, of cell volume. As such it is contingent on ecological circumstance. The nature of 'this ecological circumstance' is, however, hotly debated. Here, we investigate for angiosperms whether stomatal size may be this 'missing link': the primary determinant of genome size. Stomata are crucial for photosynthesis and their size affects functional efficiency. METHODS: Stomatal and leaf characteristics were measured for 1442 species from Argentina, Iran, Spain and the UK and, using PCA, some emergent ecological and taxonomic patterns identified. Subsequently, an assessment of the relationship between genome-size values obtained from the Plant DNA C-values database and measurements of stomatal size was carried out. KEY RESULTS: Stomatal size is an ecologically important attribute. It varies with life-history (woody species < herbaceous species < vernal geophytes) and contributes to ecologically and physiologically important axes of leaf specialization. Moreover, it is positively correlated with genome size across a wide range of major taxa. CONCLUSIONS: Stomatal size predicts genome size within angiosperms. Correlation is not, however, proof of causality and here our interpretation is hampered by unexpected deficiencies in the scientific literature. Firstly, there are discrepancies between our own observations and established ideas about the ecological significance of stomatal size; very large stomata, theoretically facilitating photosynthesis in deep shade, were, in this study (and in other studies), primarily associated with vernal geophytes of unshaded habitats. Secondly, the lower size limit at which stomata can function efficiently, and the ecological circumstances under which these minute stomata might occur, have not been satisfactorally resolved. Thus, our hypothesis, that the optimization of stomatal size for functional efficiency is a major ecological determinant of genome size, remains unproven.

Prediction of spatiotemporal patterns of neural activity from pairwise correlations.

We designed a model-based analysis to predict the occurrence of population patterns in distributed spiking activity. Using a maximum entropy principle with a Markovian assumption, we obtain a model that accounts for both spatial and temporal pairwise correlations among neurons. This model is tested on data generated with a Glauber spin-glass system and is shown to correctly predict the occurrence probabilities of spatiotemporal patterns significantly better than Ising models only based on spatial correlations. This increase of predictability was also observed on experimental data recorded in parietal cortex during slow-wave sleep. This approach can also be used to generate surrogates that reproduce the spatial and temporal correlations of a given data set.

Effect of flavonoids from various Mediterranean plants on enzymatic activity of intestinal carboxylesterase.

Flavonol compounds of three Mediterranean plants from the Algerian Atlas used traditionally in Arab folk medicine, Arenaria serpyllifolia, Rhamnus alaternus and Thapsia garganica, were found to inhibit the enzymatic activities of both rat intestine and purified porcine liver carboxylesterase in a concentration-dependent manner. Results indicate that the flavonol compounds from the aerial part of these plants lead to the inactivation of the CE pI = 5.1 with Ki of micromolar range. These results encourage us to perform further biological investigation.

[Esophageal Abrikossof tumor: a case report]. / Tumeur d'Abrikossof de l'oesophage: a propos d'un cas.

Systematic eso-gastric endoscopy allowed the discovery of a granular cell tumor. Also known as Abrikossof's tumor, the latter is a benign lesion, usually symptomless, unless it is large in size, or associated with a malignant tumor. Grossly it is a polypoid, submucosal tumor. Diagnosis is microscopic, confirmed by immunohistochemistry, unless biopsies are superficial, and show only the usually associated pseudo-carcinomatous hyperplasia. Therapeutic approach depends on the symptoms, mainly dysphagia, which is related to the size of the tumor.

Lipid synthesis and apolipoprotein gene expression in hepatocytes in primary culture from (puromycin-induced) nephrotic rats.

Primary culture of hepatocytes from puromycin aminonucleoside-induced nephrotic rats were used to discriminate between the hepatic and extra-hepatic contribution to the hyperlipidemia occurring in the nephrotic syndrome. De novo lipogenesis and utilization of exogenous fatty acids were not modified in nephrotic hepatocytes as compared to controls. In contrast 2.2 and 5.3-fold more triacylglycerol and phospholipids were secreted respectively by nephrotic hepatocytes than by controls. Triacylglycerol overproduction was not associated with an increase either in apo B mRNA level or in apo B synthesis or secretion measured by [35S]-methionine incorporation and immunoprecipitation. We also observed a significant increase in apo AI and apo E synthesis and secretion by nephrotic hepatocytes. This increase was correlated with a greater amount of apo AI and apo E mRNA than in controls. The overproduction of apo AI and apo E by nephrotic hepatocytes might intervene in the clearance of plasma lipoproteins and the redistribution of plasma cholesterol.

Direct in vivo characterization of delta 5 desaturase activity in humans by deuterium labeling: effect of insulin.

The conversion of dihomogamma linolenic acid (DHLA) into arachidonic acid (AA) was compared in normal subjects and diabetic patients before and after treatment with insulin. The kinetics of the incorporation of deuterium-labeled DHLA and its conversion product, deuterium-labeled AA, was determined in plasma triglycerides, plasma phospholipids, and platelet lipids of subjects after ingestion of 2 g of the labeled precursor. Analysis was performed by gas liquid chromatography-mass spectrometry using multiple ion detection. In normal subjects, the deuterium-labeled DHLA concentration rose to 24 to 69 mg/L in plasma triglycerides four to nine hours after ingestion and to 20 to 34 mg/L in plasma phospholipids about four hours later. Deuterium-labeled AA appeared at 12 hours, rose to 2.4 to 3.8 mg/L between 48 and 72 hours in plasma phospholipids, but remained at the limit of detection in plasma triglycerides and was undetectable in platelet lipids. In diabetic patients both before and after insulin treatment, the deuterium-labeled DHLA concentration in plasma triglycerides and in plasma phospholipids followed the same pattern as in normal subjects. However, the deuterium-labeled arachidonic acid concentration was below 1 mg/L in plasma phospholipids before insulin. After insulin treatment the patients recovered normal DHLA metabolism because deuterium-labeled AA rose in phospholipids to a mean value of 3.5 mg/L, which is in the same range as that observed in normal subjects (3.2 mg/L). The present data provide direct evidence for the conversion of DHLA into AA in humans. The effect of insulin and the data from the literature of animal studies suggest insulin dependence of delta 5 desaturase in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Enteral absorption in man of eicosapentaenoic acid in different chemical forms.

After administering the equivalent of 1 g of eicosapentaenoic acid (EPA) in four different chemical forms, the kinetics of EPA incorporation into plasma triglycerides (TG) were compared by gas liquid chromatography on a capillary column following separation of the lipid fraction by thin layer chromatography. EPA incorporation into plasma TG was markedly smaller and later when EPA was administered as an ethyl ester rather than as EPA free fatty acid, EPA arginine salt or 1,3-dioctanoyl-2-eicosapentaenoyl glycerol (2-EPA). Our results and the data in the literature are compatible with the hypothesis that 2-EPA is absorbed with minimum hydrolysis and escapes random distribution between the other positions of the glycerol molecule during the absorption process.