Electromagnetic analysis of the slotted-tube resonator with a circular cross section for MRI applications

In this paper we present electromagnetic (EM) analysis of the unloaded slotted-tube resonator (STR) with a circular cross section, using the finite element method (FEM) and method of moments (MoM) in two dimensions. This analysis allows the determination of the primary parameters: [L] and [C] matrices, optimization of the field homogeneity, and simulates the frequency response of S(11) at the RF port of the designed STR. The optimum configuration is presented, taking into account the effect of the thickness of the STR and the effect of the RF shield. As an application, we present the design results of a MRI probe using the STR and operating at 500 MHz (proton imaging at 11.74 T). The resonator has -69.37 dB minimum reflection and an unloaded quality factor (Q(o)) > 500 at 500 MHz.     

Anti-CD44-mediated blockade of leukocyte migration in skin-associated immune diseases

CD44 plays an important role in leukocyte extravasation, which is fortified in autoimmune diseases and delayed-type hypersensitivity (DTH) reactions. There is additional evidence that distinct CD44 isoforms interfere with the extravasation of selective leukocyte subsets. We wanted to explore this question in alopecia areata (AA), a hair-follicle centric autoimmune disease, and in a chronic eczema. The question became of interest because AA is treated efficiently by topical application of a contact sensitizer, such that a mild DTH reaction is maintained persistently. Aiming to support the therapeutic efficacy of a chronic eczema in AA by anti-CD44 treatment, it became essential to control whether a blockade of migration, preferentially of AA effector cells, could be achieved by CD44 isoform-specific antibodies. Anti-panCD44 and anti-CD44 variant 10 isoform (CD44v10) inhibited in vitro migration of leukocytes from untreated and allergen-treated, control and AA mice. In vivo, both antibodies interfered with T cell and monocyte extravasation into the skin; only anti-panCD44 prevented T cell homing into lymph nodes. Contributing factors are disease-dependent alterations in chemokine/chemokine receptor expression and a blockade of CD44 on endothelial cells and leukocytes. It is important that CD44 can associate with several integrins and ICAM-1. Associations depend on CD44 activation and vary with CD44 isoforms and leukocyte subpopulations. CD44 standard isoform preferentially associates with CD49d in T cells and CD44v10 with CD11b in monocytes. Accordingly, anti-panCD44 and anti-CD49d inhibit T cell, anti-CD11b, and anti-CD44v10 macrophage migration most efficiently. Thus, allergen treatment of AA likely can be supported by targeting AA T cells selectively via a panCD44-CD49d-bispecific antibody.     

Association between the 2756A> G variant in the gene encoding methionine synthase and myocardial infarction in Tunisian patients

BACKGROUND: Elevated plasma total homocysteine (tHcy), a risk factor for coronary artery disease (CAD), is due to defects in genes encoding for enzymes involved in tHcy metabolism or from inadequate status of vitamins involved in tHcy disposal. Methionine synthase (MS), a vitamin B(12)-dependent enzyme, catalyses the remethylation of homocysteine to methionine using a methyl group donated by 5-methyltetra-hydrofolate, which is the major circulating form of folate in the body. Functional genetic variants of the MS may alter tHcy as well as folate levels which are independent risk factors for CAD. The influence of a common genetic polymorphism 2756A>G of the MS gene (MTR) on plasma tHcy, folate and vitamin B(12) levels and its relation to the risk of myocardial infarction (MI) in a Tunisian case-control study was investigated. METHODS: A total of 321 Tunisian patients with MI and 343 healthy controls were included in the study. The 2756A>G variant of the MTR was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Plasma tHcy was assessed with a fluorescent polarising immunoassay method. Plasma vitamin B(12) and folate were determined by microparticular enzyme immunoassay and ion-capture, respectively. RESULTS: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 1.9% for the GG genotype, 26.2% for the AG genotype and 72% for the AA genotype. Controls had a frequency of only 0.9% for the GG genotype, 18.7% for the AG genotype and 80.5% for the AA genotype (chi(2)=6.97, p=0.03). The MI patient group showed a significant higher frequency of the G allele compared to controls (0.149 vs. 0.101; OR 1.55; 95% CI 1.10-2.18; p=0.008). The association between the 2756A>G variant in the gene encoding MS and MI was no longer significant after adjustment for other well-established risk factors. When clinical and laboratory values were compared amongst genotypes in the study groups, no significant differences were noted. CONCLUSIONS: The present study showed a significant but not independent association between the 2756A>G polymorphism of the MTR (presence of G allele) and MI in the Tunisian population.     

Évolution des paramètres anthropométriques et métaboliques après chirurgie bariatrique : expérience tunisienne monocentrique

Aims of the study

To investigate the effect of bariatric surgery on anthropometric and metabolic parameters in morbidly obese Tunisian subjects.

Intrapulmonary percussive ventilation in acute exacerbations of COPD patients with mild respiratory acidosis: a randomized controlled trial [ISRCTN17802078]

Introduction

We hypothesized that the use of intrapulmonary percussive ventilation (IPV), a technique designed to improve mucus clearance, could prove effective in avoiding further deterioration in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) with mild respiratory acidosis.

Methods

The study was performed in a medical intensive care unit of a university hospital. Thirty-three patients with exacerbations of COPD with a respiratory frequency ≥ 25/min, a PaCO₂ > 45 Torr and 7.35 ≤ pH ≤ 7.38 were included in the study. Patients were randomly assigned to receive either standard treatment (control group) or standard treatment plus IPV (IPV group). The IPV group underwent two daily sessions of 30 minutes performed by a chest physiotherapist through a full face mask. The therapy was considered successful when both worsening of the exacerbation and a decrease in pH to under 7.35, which would have required non-invasive ventilation, were avoided.

Results

Thirty minutes of IPV led to a significant decrease in respiratory rate, an increase in PaO₂ and a decrease in PaCO₂ (p < 0.05). Exacerbation worsened in 6 out of 17 patients in the control group versus 0 out of 16 in the IPV group (p < 0.05). The hospital stay was significantly shorter in the IPV group than in the control group (6.8 ± 1.0 vs. 7.9 ± 1.3 days, p < 0.05).

Conclusion

IPV is a safe technique and may prevent further deterioration in patients with acute exacerbations of COPD with mild respiratory acidosis.     

Peripheral benzodiazepine receptor-induced myocardial protection is mediated by inhibition of mitochondrial membrane permeabilization

Opening of the permeability transition pore (PTP) is a key event in ischemia-reperfusion injury and several ligands of the peripheral benzodiazepine receptor (PBR), a mitochondrial outer membrane protein possibly associated with PTP, have been demonstrated as potent cardioprotective agents. Here, we investigated the mechanisms by which the specific PBR ligand 4'-chlorodiazepam (CDZ) protected the myocardium against ischemia-reperfusion. In either global or regional models of myocardial ischemia-reperfusion in rats, CDZ reduced infarct size in a dose-dependent manner (e.g., 11 +/- 1% of the area at risk at 10 mg/kg versus 31 +/- 3% in control; p < 0.05) and to a similar extent as ischemic or diazoxide-induced preconditioning. CDZ (10 mg/kg) reduced apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining), restored mitochondrial recovery, improved oxidative phosphorylation parameters, and reduced mitochondrial membrane permeabilization with inhibition of cytochrome c and apoptosis-inducing factor releases. CDZ increased the resistance of mitochondria to Ca2+-induced PTP opening. All these cardioprotective effects of CDZ were associated with an improved stabilization of the association of Bcl-2 with the mitochondrial membrane and inhibition of the association of a cytosolic fragment of Bax, occurring during ischemia-reperfusion, with the outer mitochondrial membrane. In addition, the PTP opener atractyloside (20 microM) and the Bcl-2 inhibitor ethyl-2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1) (20 microM) abrogated CDZ-induced reduction of infarct size. These results demonstrate that PBR occupancy by CDZ renders the heart more resistant to ischemia-reperfusion injury by limiting mitochondrial membrane permeabilization. This is due to a reorganization of the balance between pro- and antiapoptotic proteins of the Bcl-2 family proteins at the level of mitochondrial membranes.     

Pitfalls in molecular diagnosis of Friedreich ataxia

Freidreich ataxia (FRDA) is the most common hereditary ataxia, nearly 98% of patients harbouring homozygous GAA expansions in intron 1 of the FXN gene (NM_000144.4). The remaining patients are compound heterozygous for an expansion and a point mutation or an exonic deletion. Molecular screening for FXN expansion is therefore focused on (GAA)n expansion analysis, commonly performed by triplet repeat primed PCR (PT-PCR).We report on an initial pitfall in the molecular characterization of a 15 year-old girl with Freidreich ataxia (FRDA) who carried a rare deletion in intron 1 of the FXN gene. Due to this deletion TP-PCR failed to amplify the GAA expansion. This exceptional configuration induced misinterpretation of the molecular defect in this patient, who was first reported as having no FXN expansion. NGS analysis of a panel of 212 genes involved in nuclear mitochondrial disorders further revealed an intragenic deletion encompassing exons 4–5 of the FXN gene. Modified TP-PCR analysis confirmed the presence of a classical (GAA)n expansion located in trans. This case points out the possible pitfalls in molecular diagnosis of FRDA in affected patients and their relatives: detection of the FXN expansion may be impaired by several non-pathological or pathological variants around the FXN (GAA)n repeat. We propose a new molecular strategy to accurately detect expansion by TP-PCR in FRDA patients.     

Increased endogenous carbon monoxide production in severe sepsis

OBJECTIVE: A comparison was made between the endogenous carbon monoxide (CO) production in mechanically ventilated critically ill adult patients with, and those without, severe sepsis. DESIGN: Prospective comparative study. SETTING: Medical ICU in a community hospital. PATIENTS: Twenty-four patients with severe sepsis of various etiologies and five control patients with varying diagnoses. INTERVENTION: CO concentration was determined with an infrared CO analyzer on exhaled breath collected at the outlet of the ventilator. Endogenous CO production was estimated by the lung CO excretion rate measured at steady state. MEASUREMENTS AND MAIN RESULTS:: Endogenous CO production was higher in the sepsis group during the first 3 days of treatment in comparison to the control group (10.9+/-5 (SD) microl/kg per h on day 1, 7.8+/-4.9 microl/kg per h on day 2 and 6.9+/-4.7 microl/kg per h on day 3 versus 2.1+/-0.5 microl/kg per h; p<0.01 for each comparison). Survivors of sepsis had a significantly higher endogenous CO production on day 1 compared to non-survivors (14.7+/-5.3 versus 8.5+/-3.3 microl/kg per h; p=0.02). CONCLUSION: Endogenous CO production was significantly higher in mechanically ventilated patients suffering from severe sepsis. Further studies are required in order to determine the mechanism(s) and the functional significance of this increase.     

Platelet Activating Factor (PAF) Receptor Deletion or Antagonism Attenuates Severe HSV-1 Meningoencephalitis

Herpes simplex virus type 1 (HSV-1) is a human pathogen that may cause severe encephalitis. The exacerbated immune response against the virus contributes to the disease severity and death. Platelet activating factor (PAF) is a mediator capable of inducing increase in vascular permeability, production of cytokines on endothelial cells and leukocytes. We aimed to investigate the activation of PAF receptor (PAFR) and its contribution to the severity of the inflammatory response in the brain following HSV-1 infection. C57BL/6 wild-type (WT) and PAFR deficient (PAFR^?/?) mice were inoculated intracranially with 10⁴ plaque-forming units (PFU) of HSV-1. Visualization of leukocyte recruitment was performed using intravital microscopy. Cells infiltration in the brain tissue were analyzed by flow cytometry. Brain was removed for chemokine assessment by ELISA and for histopathological analysis. The pharmacological inhibition by the PAFR antagonist UK-74,505 was also analyzed. In PAFR^?/? mice, there was delayed lethality but no difference in viral load. Histopathological analysis of infected PAFR^?/? mice showed that brain lesions were less severe when compared to their WT counterparts. Moreover, PAFR^?/? mice showed less TCD4⁺, TCD8⁺ and macrophages in brain tissue. This reduction of the presence of leukocytes in parenchyma may be mechanistically explained by a decrease in leukocytes rolling and adhesion. PAFR^?/? mice also presented a reduction of the chemokine CXCL9 in the brain. In addition, by antagonizing PAFR, survival of C57BL/6 infected mice increased. Altogether, our data suggest that PAFR plays a role in the pathogenesis of experimental HSV-1 meningoencephalitis, and its blockade prevents severe disease manifestation.     

Lúpus eritematoso sistêmico bolhoso em gestante: relato de caso*

Systemic lupus erythematosus (SLE) can cause numerous skin lesions. Despite being rare, lupus-specifi c bullous lesions demonstrate characteristic clinical and immunopathological features and require differential diagnosis among numerous bullous conditions that may overlap with SLE. The present study presents a case of bullous systemic lupus erythematosus (BSLE) in a pregnant woman.