Effects of increasing doses of alpha-tocopherol in providing protection of low-density lipoprotein from oxidation

Taking for granted the sensitivity of the Quantitative Buffy Coat (QBC) system, as documented in a murine experimental model, we assayed to detect Trypanosoma cruzi in the peripheral blood of 100 patients with Chagas disease in its chronic phase. By means of the method, no positivity occurred, evently as a consequence of small parasitemias, undetectable by this technique as assessed by the cases in consideration.     

Complications of surgery for epiretinal membranes

PURPOSE: Surgery has been successful in removing epiretinal membranes (ERM) from the macula, allowing some improvement in vision in 80-90% of patients; however, complications are relatively frequent. We conducted a retrospective study to evaluate the rate of peri- and postoperative complications and their influence on functional outcome of eyes having been operated on for ERM. MATERIAL AND METHODS: Preoperative findings, intraoperative and postoperative complications as final results of 70 consecutive cases of idiopathic or secondary ERM operated on by the same retina surgeon were analyzed. RESULTS: In all cases the ERMs were successfully removed from the fovea. The mean visual acuity (VA) increased from 0.34 +/- 0.2 to 0.54 +/- 0.31 (P < 0.05) postoperatively. Idiopathic and secondary ERM both showed significant improvement after surgery. Complications included intraoperative hemorrhage and retinal tears and postoperative progressive nuclear sclerosis, retinal tears causing detachments, macular edema and retinal pigmentary epitheliopathy. Final VA was not significantly different from the mean after complications, apart from when retinal detachments involved the macular area. CONCLUSIONS: Performing surgery for ERM is worthwhile in eyes with major decreased VA and in eyes with metamorphopsia but only moderately reduced vision. Postoperative complications are frequent but can usually be managed successfully. Of them, only retinal detachment has a negative effect on the final functional outcome.     

Interleukin-6 and small intestinal luminal immunoglobulins

Our aim was to determine the relationships between interleukin-6 and immunoglobulin levels within small intestinal luminal secretions. Twenty adult subjects with small intestinal bacterial overgrowth (N = 13), irritable bowel syndrome (N = 4), and nonulcer dyspepsia (N = 3) underwent endoscopic aspiration of secretions from the small intestinal mucosal surface for assessment of IL-6, IgA1, IgA2, IgM, IgG1, IgG2, IgG3, and IgG4 concentrations. Serum immunoglobulin concentrations and small intestinal histology were also determined. IgA2 and IgG3 were the predominant IgA and IgG subclasses in luminal secretions in 19/20 (95%) and 20/20 (100%) subjects, respectively. IgA1 and IgG1 predominated in serum in all subjects. No subject had villous atrophy. Luminal IL-6 concentrations correlated significantly with luminal IgA2, IgM, and IgG3 concentrations but not with IgA1 or any other IgG subclass levels. Conversely, luminal IL-6 or immunoglobulin concentrations did not correlate significantly with levels of any immunoglobulin isotype in serum. These observations suggest that important relationships exist between local IL-6 and IgA2, IgM, and IgG3 responses in human small intestinal luminal secretions. Local investigation is mandatory when assessing intestinal immune activity.     

Inhibition of repetitive thrombus formation in the stenosed canine coronary artery by enoxaparin, but not by unfractionated heparin

Experiments were designed to compare the antithrombotic efficacy of enoxaparin and unfractionated heparin (UH) in a model of platelet-dependent cyclic flow reductions (CFRs) in the stenosed canine circumflex coronary artery. Low-molecular-weight heparins (LMWHs) are safe and effective in the prevention and treatment of venous thromboembolism. The present experiments were designed to evaluate the potential use of LMWHs in arterial thrombotic indications by comparing the antithrombotic effect of an LMWH with that of UH in an animal model of unstable angina. After establishment of consistent CFRs by experimentally induced vascular stenosis and damage, vehicle (saline), enoxaparin, or UH was administered intravenously as a loading dose plus a continuous infusion for 1 hour. The inhibition of CFRs was taken as an indicator of antithrombotic efficacy. Enoxaparin inhibited repetitive platelet thrombus formation in a dose-dependent manner, with significant inhibition of CFRs achieved at 0.5 mg/kg + 5 microg/kg per minute. This dose of enoxaparin resulted in anti-Xa levels of 0.9 to 1.0 IU/mL, anti-IIa levels of 0.2 to 0.3 IU/mL, activated partial thromboplastin time (APTT) of 1.3-fold over baseline, and a 1.4-fold increase (NS) in template bleeding time. Near-complete abolishment of CFRs was achieved with enoxaparin at 1.0 mg/kg + 10 microg/kg per minute. This dose of enoxaparin produced anti-Xa levels of 2 to 2.2 IU/mL, anti-IIa levels of 0.5 to 0.6 IU/mL, an increase in APTT of 1.4- to 1.5-fold over baseline, and a 1.9-fold increase (P<0.05) in template bleeding time. In contrast, UH had no significant effect on CFRs at a dose (100 U/kg + 10 U/kg per minute) that resulted in anti-Xa levels of 1.2 to 1.6 IU/mL, anti-IIa levels of 1.8 to 2.4 IU/mL, an increase in APTT greater than 10-fold over baseline, and a 2.5-fold increase (P<0.05) in template bleeding time. Compared with the vehicle group, circulating platelet count and hematocrit were not changed significantly by any dose of enoxaparin or UH tested. Enoxaparin, unlike UH, prevented repetitive platelet-dependent thrombus formation in the dog, thereby supporting the potential use of enoxaparin as a replacement for heparin in the treatment of arterial thrombotic disorders such as unstable angina.     

Cell-contact-stimulated formation of filamentous appendages by Salmonella typhimurium does not depend on the type III secretion system encoded by Salmonella pathogenicity island 1

The formation of filamentous appendages on Salmonella typhimurium has been implicated in the triggering of bacterial entry into host cells (C. C. Ginocchio, S. B. Olmsted, C. L. Wells, and J. E. Galán, Cell 76:717-724, 1994). We have examined the roles of cell contact and Salmonella pathogenicity island 1 (SPI1) in appendage formation by comparing the surface morphologies of a panel of S. typhimurium strains adherent to tissue culture inserts, to cultured epithelial cell lines, and to murine intestine. Scanning electron microscopy revealed short filamentous appendages 30 to 50 nm in diameter and up to 300 nm in length on many wild-type S. typhimurium bacteria adhering to both cultured epithelial cells and to murine Peyer's patch follicle-associated epithelia. Wild-type S. typhimurium adhering to cell-free culture inserts lacked these filamentous appendages but sometimes exhibited very short appendages which might represent a rudimentary form of the cell contact-stimulated filamentous appendages. Invasion-deficient S. typhimurium strains carrying mutations in components of SPI1 (invA, invG, sspC, and prgH) exhibited filamentous appendages similar to those on wild-type S. typhimurium when adhering to epithelial cells, demonstrating that formation of these appendages is not itself sufficient to trigger bacterial invasion. When adhering to cell-free culture inserts, an S. typhimurium invG mutant differed from its parent strain in that it lacked even the shorter surface appendages, suggesting that SPI1 may be involved in appendage formation in the absence of epithelia. Our data on S. typhimurium strains in the presence of cells provide compelling evidence that SPI1 is not an absolute requirement for the formation of the described filamentous appendages. However, appendage formation is controlled by PhoP/PhoQ since a PhoP-constitutive mutant very rarely possessed such appendages when adhering to any of the cell types examined.     

Development and validation of transient isotachophoretic capillary zone electrophoresis for determination of peptides

Although capillary zone electrophoresis (CZE) is known for its high resolution power and low mass detection limits, the concentration detection limits are rather poor when ultraviolet absorbance detection is used. To overcome this limitation, several on-column transient isotachophoresis (tITP) protocols have been developed and validated for the determination of both cationic and anionic model peptides, separately. Using this preconcentration method, up to 72% of the capillary can be filled with sample solution, without any loss in resolution. Thus, without any modification of the hardware set-up, the sensitivity is increased about two orders of magnitude. For the model cationic peptides (gonadorelin, angiotensin II) good linearity and reproducibility is observed in the 20 to 100 ng/mL concentration range. For the anionic peptides (N-t-Boc-Pentagastrin and two related peptides), a tITP method was developed using a dynamically coated capillary. The coating was prepared by adding Fluorad FC-135 to the leading electrolyte buffer. In this way a positively charged bilayer was formed on the inside of the capillary, producing an electroosmotic flow towards the outlet using reversed polarity conditions. In this way, acceptable analysis times were achieved. Using the developed tITP method, up to 72% of the capillary can be filled with sample solution as well. The anionic peptides are separated even better than when using CZE conditions. Linearity and reproducibility in the 20-100 ng/mL range proved to be excellent.     

The relationship of local and distant failure from endometrial cancer: defining a clinical paradigm

Water-soluble amyloid beta-peptides (sA beta), ending at residue 42, precede amyloid plaques in Down's syndrome (DS). Here we report that sA beta consists of the full-length A beta(1-42) and peptides truncated and modified by cyclization of the N-terminal glutamates, A beta[3(pE)-42] and A beta[11(pE)-42]. The A beta[3(pE)-42] peptide is the most abundant form of sA beta in Alzheimer's disease (AD) brains. In DS, sA beta[3(pE)-42] concentration increases with age and the peptide becomes a dominant species in the presence of plaques. Both pyroglutamate-modified peptides and the full-length A beta form a stable aggregate that is water soluble. The findings point to a crucial role of the aggregated and modified sA beta in the plaque formation and pathogenesis of AD.     

Identification and simulation of new non-random statistical properties common to different populations of eukaryotic non-coding genes

The autocorrelation function analysing the occurrence probability of the i-motif YRY(N)iYRY in genes allows the identification of mainly two periodicities modulo 2, 3 and the preferential occurrence of the motif YRY(N)6YRY (R = purine = adenine or guanine, Y = pyrimidine = cytosine or thymine, N = R or Y). These non-random genetic statistical properties can be simulated by an independent mixing of the three oligonucleotides YRYRYR, YRYYRY and YRY(N)6 (Arquès & Michel, 1990b). The problem investigated in this study is whether new properties can be identified in genes with other autocorrelation functions and also simulated with an oligonucleotide mixing model. The two autocorrelation functions analysing the occurrence probability of the i-motifs RRR(N)iRRR and YYY(N)iYYY simultaneously identify three new non-random genetic statistical properties: a short linear decrease, local maxima for i identical to 3[6] (i = 3, 9, etc) and a large exponential decrease. Furthermore, these properties are common to three different populations of eukaryotic non-coding genes: 5' regions, introns and 3' regions (see section 2). These three non-random properties can also be simulated by an independent mixing of the four oligonucleotides R8, Y8, RRRYRYRRR, YYYRYRYYY and large alternating R/Y series. The short linear decrease is a result of R8 and Y8, the local maxima for i identical to 3[6], of RRRYRYRRR and YYYRYRYYY, and the large exponential decrease, of large alternating R/Y series (section 3). The biological meaning of these results and their relation to the previous oligonucleotide mixing model are presented in the Discussion.     

Context-Aware Routing in Delay and Disruption Tolerant Networks

In this paper, we analyze the problem of context adaptation in delay and disruption tolerant networks (DTNs). Initially, we performed experiments with well-known routing protocols to evaluate how much distinct configurations impact their performance. The results show that the performance is highly configuration dependent and improper configuration can lead to a performance up to 506.6 % worse than the best configuration tested. This motivates us to propose CARTOON (context-aware routing protocol for opportunistic networks), a novel routing protocol for DTNs based on the concept of context-adaptation. We evaluate CARTOON through simulations and the results show that our propose outperformed other well-known protocols, exhibiting results that are, on average, at 95 % of the computed optimum delivery rate.     

Localization of calretinin mRNA in rat and guinea pig inner ear by in situ hybridization using radioactive and non-radioactive probes

The localization of calretinin mRNA was studied in the rat and guinea pig inner ear by in situ hybridization, and compared to the distribution of the protein previously examined by immunocytochemistry. Radioactive and non-radioactive in situ hybridization (ISH) were performed using oligonucleotide probes labelled with 35S or digoxigenin. Radioactive ISH was more sensitive than non-radioactive ISH. In cochlear and vestibular ganglia, calretinin mRNA was localized in subpopulations of neurons with patterns of distribution similar to those shown by immunocytochemistry. By contrast, the observations in the sensory epithelia differed with the two techniques, ISH revealing less positive structures than immunocytochemistry. Rat inner hair cells and guinea pig inner hair cells, Hensen's cells and Deiters cells, which had been described strongly immunoreactive, appeared positive with radioactive but not with non-radioactive ISH. On the other hand, rat vestibular type II hair cells and guinea pig interdental cells of the spiral limbus which were faintly immunoreactive were not positive with both ISH techniques.