Collagen XVIII/endostatin is associated with the epithelial-mesenchymal transformation in the atrioventricular valves during cardiac development.

Type XVIII collagen is a multidomain protein that contains cleavable C-terminal NC1 and endostatin fragments, which have been shown to either induce or inhibit cell migration. Endostatin is being intensely studied because of its anti-angiogenic activity. Three variants of type XVIII collagen have been reported to be distributed in epithelial and endothelial basement membranes in a tissue-specific manner. The single gene encoding collagen XVIII is on chromosome 21 within the region associated with the congenital heart disease phenotype observed in Down's syndrome. In this study, we investigated the expression pattern of collagen XVIII in embryonic mouse hearts during formation of the atrioventricular (AV) valves. We found that collagen XVIII is localized not only in various basement membranes but is also highly expressed throughout the connective tissue core of the endocardial cushions and forming AV valve leaflets. It was closely associated with the epithelial-mesenchymal transformation of endothelial cells into mesenchymal cushion tissue cells and was localized around these cells as they migrated into the cardiac jelly to form the initial connective tissue elements of the valve leaflets. However, after embryonic day 17.5 collagen XVIII expression decreased rapidly in the connective tissue and thereafter remained detectable only in the basement membranes of the endothelial layer covering the leaflets. The staining pattern observed within the AV endocardial cushions suggests that collagen XVIII may have a role in cardiac valve morphogenesis. These results may help us to better understand normal heart development and the aberrant mechanisms that cause cardiac malformations in Down's syndrome.     

A sensitive reverse ELISA for the measurement of specific IgE to Der p 2, a major Dermatophagoides pteronyssinus allergen.

BACKGROUND: Epidemiologic studies have shown that the presence of IgE antibodies to house dust mite and other indoor allergens is an important risk factor for asthma. OBJECTIVE: The aim of this study was to develop a reverse ELISA (rELISA) for measuring specific IgE to Der p 2, a major Dermatophagoides pteronyssinus (Dpt) allergen, as a potential tool for followup of allergen immunotherapy. METHODS: Recombinant Der p 2 allergen or a monoclonal antibody to Der p 2 was used to coat plates in conventional ELISA (cELISA) and rELISA, respectively. Sera from 48 asthmatic patients with positive skin prick test (SPT+) to D. pteronyssinus extract were analyzed for total IgE and specific IgE to Der p 2, and the results were compared with a group of 41 SPT asthmatic and 30 SPT- control subjects. RESULTS: The sensitivity of the two assays for Der p 2-specific IgE was 3.9 EU/mL and their specificities were confirmed by inhibition tests, in a dose-dependent manner. There was a significant positive correlation between cELISA and rELISA (r = 0.74; P < 0.0001). However, rELISA was more sensitive than was cELISA, regarding both the positive sera percentage (70.8% vs 52.1%) and the Der p 2-specific IgE levels (28.4 vs 4.5 EU/mL) in SPT+ asthmatic patients. CONCLUSIONS: rELISA has shown to be a sensitive and alternative method for measuring Der p 2-specific IgE without using radioactive techniques. Detection of specific IgE to major allergens and relevant peptides, and identification of B cell epitopes in allergens will provide valuable information for the design of allergen analogs and peptides for immunotherapy.     

Genotoxic and mutagenic effects of fipronil on mice

The toxic effects of several compounds on ecosystems are not restricted to ecological disturbances, and may also affect long-term human health. Fipronil is highly efficient in the control of pests, including those resistant to pyrethroid, organophosphate, and carbamate insecticides. Relatively little is known about the action of fipronil in vertebrates. This study was aimed to evaluate the genotoxic and mutagenic potential of this compound in mice exposed to different doses and demonstrates the damage caused by fipronil on non-target organisms in artificial conditions. Mice were divided into five groups: group I = 30% of DL₅₀ (15 mg/kg), group II = 50% of the DL₅₀ (25 mg/kg), group III = DL₅₀ (50 mg/kg), group IV = negative control, and group V = positive control. Peripheral blood was collected for the comet assay (24 h after exposure) and the micronucleus test (24, 48 and 72 h after exposure). Our findings revealed that doses of 15 mg/kg (group I) and 25 mg/kg (group II) of fipronil did not have genotoxic or mutagenic effects. Only the highest dose tested (50 mg/kg) induced DNA damage 24 h after exposure, indicating the mutagenic potential of fipronil. Therefore, this or higher doses are not recommended, as they may be toxic to non-target organisms.     

Gliomatosis cerebri: diagnostic considerations in three cases

Clinical symptoms and radiologic characteristics of gliomatosis cerebri (GC) are non-specific and the condition may be confused with other central nervous system diseases. We report three patients with GC; all the three patients had involvement of more than three lobes and the deep white matter, as well as bilateral involvement. Differentiation of GC from other neurologic diseases involving diffuse white matter may be difficult. However, the diagnosis can be based on the combination of radiologic and histopathologic features.     

Appraisal of the antichemotactic activity of flavonoids on polymorphonuclear neutrophils

Flavonoids are polyphenols that are ubiquitous in plants and frequently consumed in the diet. They are suggested to have many beneficial actions on human health, including anti-inflammatory activity. Their properties have been studied in a number of cell types, but little is known about their effects on neutrophil biology. Consequently, we selected 25 flavonoids with different structural features to evaluate their in vitro inhibition of rat polymorphonuclear neutrophil (PMN) chemotaxis, employing a modified Boyden chamber. Migratory activity was measured towards a chemotactic stimulant, formyl-Met-Leu-Phe or lipopolysaccharide. Furthermore, the cytotoxic effect of flavonoids on PMNs was determined by the release of cytosolic lactate dehydrogenase (LDH). Ten flavonoids significantly retarded the migration of PMNs with at least one of the concentrations tested in a range between 0.625 and 100 μM; the best antichemotactic agents were flavone, flavonol, quercetin and rutin. None of the flavanones evaluated presented any significant inhibition of migration in this assay. Our findings indicated that non-hydroxylated flavones possess a better antichemotactic activity when compared to flavones with hydroxy groups. The presence of a sugar moiety in rutin did not produce any increase in this effect, when compared to the respective aglycone analogue. Finally, none of the flavonoids exhibited cell toxicity and for many of these flavonoids this is the first report of the inhibition of PMN chemotaxis.     

Action of permethrin on Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae) semi-engorged females: Morpho-physiological evaluation of salivary glands

Currently the most effective method of tick control is the use of acaricides, among which stands out permethrin (active ingredient of acaricide Advantage^® Max3, Bayer), a neurotoxic pyrethroid. However, assessments of their effects on other tick systems such as glandular are still scarce. Thus, this study provides information, through histochemical techniques, about the toxic effect of this pyrethroid on the morphophysiology of salivary glands of semi-engorged Rhipicephalus sanguineus females exposed to different concentrations of permethrin (206, 1031, and 2062 ppm). The results showed that permethrin caused significant changes in the salivary gland metabolism accelerating the process of glandular degeneration, an event which would occur naturally and with great intensity only in the final engorgement stage. Furthermore, this study pointed out that permethrin reduces the salivary gland secretion ability through a drastic reduction of proteins, lipids, and polysaccharides in acinar cells. These changes impair the females to finalize the feeding process, what indirectly affects the reproductive process.     

Levels of GM-CSF, IL-3, and IL-6 in fluid and tissue from human radicular cysts

Cytokines released by immune system cells play an important role in cyst enlargement. This study aimed to determine, by ELISA, the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and IL-6 in fluid and tissue from human radicular cysts. GM-CSF was found in 42.8% of the fluid samples (164.3 pg/mL) and IL-6 in 92.8% (641.4 pg/mL). No IL-3 was detected in any fluid samples. In the tissue samples, 28.6% were positive for IL-3 (369.2 pg/mL), 86.4% for IL-6 (92.4 pg/mL), and 95.8% for GM-CSF (200.5 pg/mL). It can be concluded that GM-CSF and IL-6 were widely found in the fluid and tissue samples. In contrast, IL-3 was found only in the cystic tissue, even though in few lesions. These cytokines may contribute to the inflammation, cystic growth, and bone resorption that characterize cystic lesions.     

Safety and effectiveness of single- versus triple-dose gadodiamide injection- enhanced MR angiography of the abdomen: a phase III double-blind multicenter study

PURPOSE: To evaluate the safety and effectiveness of gadodiamide-enhanced magnetic resonance (MR) angiography with single and triple doses in the assessment of abdominal arterial stenoses. MATERIALS AND METHODS: One hundred five patients were included in the randomized, double-blind, phase III multicenter trial. Results of MR angiography with 0.1 mmol/kg and 0.3 mmol/kg doses of gadodiamide were compared with those of digital subtraction angiography (DSA) and according to dose. RESULTS: No serious adverse events were observed. The mean contrast index at the region proximal to the primary stenosis was significantly higher in the triple-dose group (P =.03). Mean 95% CI values for the difference in depicted degree of stenosis between DSA and postcontrast MR angiography improved from -3.4% +/- 4.7 (SD) in the single-dose group to -1.2% +/- 4.7 in the triple-dose group. Mean values for overall image quality on the visual analogue scale improved with the triple dose (P =.02). Confidence in diagnosis was high at postcontrast MR angiography in 88% and 96% of cases in the single- and triple-dose groups, respectively. CONCLUSION: Gadodiamide-enhanced MR angiography performed with single and triple doses is safe and effective for assessing major abdominal arterial stenoses. Although high agreement between MR angiography and DSA was achieved with both doses, triple-dose MR angiography was superior in the evaluations of image quality, degree of arterial stenoses, and confidence in diagnosis.