Measurement of strain exerted on blood vessel walls by double-quantum-filtered 2H NMR

In this study ²H double quantum-filtered (DQF) NMR spectros-copy of water molecules inside the blood vessel wall was used to monitor structural changes after the application of strain. This method was applied to a variety of bovine large blood vessels, including aorta, coronary artery, carotid artery, and vena cava. Inducing strain in coronary arteries by inflating them by air or water revealed dramatic changes in the ²H DQF spectral lineshapes. Uniaxial extensions of longitudinal and circumferential strips led to distinct spectral responses for the different blood vessels. While the spectral lineshapes for the coronary and the carotid arteries were very sensitive to longitudinal strain, they were not affected by circumferential stretching. For the aorta there were no changes in the line-shape upon strain. For the vena cava a large effect of strain was found that was independent of the choice of elongation axis. The effect of elongation on the spectra was assigned to the outer layer, the adventitia, whereas spectral lineshapes that originated from inner layers, media and intima, were almost insensitive to strain. Angular dependence experiments proved the presence of macroscopic order in the strained state superimposed on a broad distribution of the local directors. Our results demonstrate the sensitivity of ²H DQF NMR as a probe for dynamic processes occurring on the microscopic scale in a molecular network. Key words: blood vessels; strain; double-quantum; ²H NMR.     

Liver transplantation for cardiac failure in patients with hereditary hemorrhagic telangiectasia.

Liver involvement in hereditary hemorrhagic telangiectasia may lead to high-output cardiac failure. Few data have been reported on orthotopic liver transplantation (OLT) for these patients. In this paper, we describe two patients treated by OLT as a salvage procedure for cardiac failure, and we review literature on this subject. Our two patients resumed normal cardiac function after OLT. This procedure appears to be a promising therapy with good long-term results despite dissection difficulties encountered due to the collateral arterial network reorganization.     

Lesion of the anteroventral third ventricle region impairs the recovery of arterial pressure induced by hypertonic saline in rats submitted to hemorrhagic shock

The effect of intravenous infusion of hypertonic saline (HS, 7.5% NaCl) on the recovery of mean arterial pressure (MAP) after hemorrhage was studied in sham-operated rats and in rats with electrolytic lesion of the anteroventral third ventricle (AV3V) region (4 h, 4 and 20 days). Rats anesthetized with thiopental sodium were bled (about 2.8 ml/100 g) until the MAP was stabilized at the level of 60 mmHg for 30 min. In sham-lesioned rats. MAP increased to 90 mmHg and became stable near this level after intravenous infusion of 7.5% NaCl (4 ml/kg b.wt.). In AV3V-lesioned rats, the same infusion induced a smaller increase in MAP (80 mmHg) and the MAP returned to pre-infusion levels within 30 min. These results show that the AV3V region plays an important role in the recovery of arterial pressure induced by hypertonic saline in rats submitted to hemorrhagic shock.     

Absence of mutations in the homeodomain of the MSX1 gene in patients with hypodontia

Hypodontia, the congenital absence of one or a few permanent teeth, is one of the most frequent alterations of the human dentition. Although hypodontia does not represent a public health problem, it may cause both speech and masticatory dysfunction and esthetic problems. A missense mutation in the homeodomain of MSX1 gene has been associated with hypodontia of second premolars and third molars in humans. However, another study excluded this gene as causative locus for hypodontia of incisors and premolars. To further investigate the role of the MSX1 gene in human hypodontia, we analyzed the homeobox region of the MSX1 gene in 20 individuals with different patterns of familial or isolated hypodontia. The direct sequencing of PCR products did not show any polymorphisms or mutations in the human MSX1 gene. Our results indicate that inactivation of MSX1 gene in humans must have a highly selective effect on dentition, and other genes must be involved in the cause of hypodontia in humans.     

Pharmacological and genetic modifications of somatic cholesterol do not substantially alter the course of CNS disease in Niemann–Pick C mice

Niemann–Pick type C (NPC) is a neurodegenerative disorder with somatically altered cholesterol metabolism. The NPC1 gene has recently been cloned and shown to have sequences shared with known sterol-sensing proteins. We have used a mouse model with a disrupted Npc1 gene to study two cholesterol-lowering drugs (nifedipine and probucol) and the effects of introducing a null mutation in the low-density lipoprotein receptor (LDLR). Although these treatments significantly ameliorated liver cholesterol storage, little effect on the onset of neurological symptoms was found.     

Angioedema related to the use of streptokinase

Angioedema is a rare reaction to streptokinase, acute and potentially fatal, which should be quickly diagnosed and treated to guarantee the best prognosis for the patient. We describe here the case of a 65-year-old man, who displayed an anaphylactic reaction after the beginning of thrombolysis with streptokinase, which was quickly treated, and remained hospitalized for one week in the Intensive Care Unit.     

Effect of a beta-lapachone-derived naphthoimidazole on Trypanosoma cruzi: identification of target organelles

OBJECTIVES: Investigation of the mode of action of the naphthoimidazole N1, obtained from the reaction of beta-lapachone with benzaldehyde, which among 45 semi-synthetic derivatives of naphthoquinones isolated from Tabebuia sp. was one of the most active compounds against Trypanosoma cruzi trypomastigotes. METHODS: Quantification of the effect of N1 against the proliferative forms of T. cruzi, and investigation of potential targets in the parasite using electron microscopy and flow cytometry techniques. RESULTS: N1 presented the following order of activity: amastigotes > trypomastigotes > epimastigotes. The effect on intracellular forms was approximately 25 times higher than on macrophages and heart muscle cells. N1-treated parasites presented an abnormal chromatin condensation and mitochondrial damage. In epimastigotes, alterations of reservosomes were observed, and in trypomastigotes, a decrease in the electron density of acidocalcisomes was observed. In epimastigotes, the naphthoimidazole inhibited the activity of succinate cytochrome c reductase. Labelling with rhodamine 123 or Acridine Orange was decreased in both forms treated with N1. CONCLUSIONS: The results suggest that epimastigotes, reservosomes, mitochondrion, and nucleus contain N1 targets. In trypomastigotes, in which reservosomes are absent, the organelles affected by the compound were also the mitochondrion and nucleus, as well as acidocalcisomes, in which the decrease in electron density could be due to the use of polyphosphate as an alternative energy supply.