A microprocessor-controlled tracheal insufflation-assisted total liquid ventilation system

A prototype time cycled, constant volume, closed circuit perfluorocarbon (PFC) total liquid ventilator system is described. The system utilizes microcontroller-driven display and master control boards, gear motor pumps, and three-way solenoid valves to direct flow. A constant tidal volume and functional residual capacity (FRC) are maintained with feedback control using end-expiratory and end-inspiratory stop-flow pressures. The system can also provide a unique continuous perfusion (bias flow, tracheal insufflation) through one lumen of a double-lumen endotracheal catheter to increase washout of dead space liquid. FRC and arterial blood gases were maintained during ventilation with Rimar 101 PFC over 2–3 h in normal piglets and piglets with simulated pulmonary edema induced by instillation of albumin solution. Addition of tracheal insufflation flow significantly improved the blood gases and enhanced clearance of instilled albumin solution during simulated edema.     

Potts Anastomosis for Children with Idiopathic Pulmonary Hypertension

Mortality in children with idiopathic pulmonary arterial hypertension is high, emphasizing the need for novel therapeutic approaches. A surgical approach consisting in the creation of anastomosis between descending aorta and left pulmonary artery, the Potts shunt, has been proposed to decompress right ventricle. We reported two cases of severe idiopathic pulmonary hypertension in children with right heart failure refractory to medical treatment who benefited of Potts shunt.     

Inhibition of the binding of HCV serum particles to human hepatocytes by E1E2‐specific D32.10 monoclonal antibody

The aim of this study was to determine the inhibition of binding activity of the monoclonal antibody (mAb) D32.10 which recognizes a highly conserved discontinuous antigenic determinant (E1:297–306, E2:480–494, and E2:613–621) expressed on the surface of serum‐derived HCV particles (HCVsp) of genotypes 1a, 1b, 2a, and 3a. To this end, an in vitro direct cell‐binding assay based on the attachment of radiolabeled HCVsp was developed, and Scatchard plots were used to analyze ligand–receptor binding data. HCV adsorption was also assessed by quantitating cell‐associated viral RNA by a real‐time RT‐PCR method. Saturable concentration‐dependent specific binding of HCVsp to Huh‐7 or HepaRG cells was demonstrated. The Scatchard transformed data showed two‐site interaction for Huh‐7 and proliferative HepaRG cells: the high‐affinity binding sites (K_d1 = 0.1–0.5 µg/ml) and the low‐affinity binding sites (K_d1 = 5–10 µg/ml), and one‐site high‐affinity binding model between E1E2/D32.10‐positive HCVsp and hepatocyte‐like differentiated HepaRG cells. The E1E2‐specific mAb D32.10 inhibited efficiently (>60%) and selectively the binding with an IC₅₀ ≤0.5 µg/ml in all the experimental approaches using serum HCV of genotype either 3 or 1b. This supports the involvement of the E1E2/D32.10 discontinuous antigenic determinant in the interactions between human hepatocytes and HCVsp, and suggests that D32.10‐like antibodies present in sera from patients infected with HCV could play a protective role. J. Med. Virol. 81:1726–1733, 2009. © 2009 Wiley‐Liss, Inc.     

New trends in dual 5-LOX/COX inhibition

Dual inhibitors are drugs able to block both the COX and the 5-LOX metabolic pathways. The interest of developing such compounds is supported by a large number of pharmacological studies. Compared to COX or LOX pathways single inhibitors, dual inhibitors present at least two major advantages. First, dual inhibitors, by acting on the two major arachidonic acid metabolic pathways, possess a wide range of anti-inflammatory activity. Secondly, dual inhibitors appear to be almost exempt from gastric toxicity, which is the most troublesome side effect of COX inhibitors. The mechanism of their gastric-sparing properties is not completely understood, although it has been demonstrated that leukotrienes significantly contribute to the gastric epithelial injury. Finally, both COX and LOX derivatives (prostanoids and leukotrienes, respectively) are involved in other diseases than inflammation such as cancer proliferation where the use of dual inhibitors could be an interesting approach.     

Risk factors for maternal thromboembolism: obstetrical circumstances

We analyzed the statistical relationship described between the principal laboratory anomalies related to thrombophilia and obstetrical pathology and risk of maternal thromboembolism.     

Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine

Amputation of the zebrafish caudal fin stimulates regeneration of the dermal skeleton and reexpression of sonic hedgehog (shh)-signaling pathway genes. Expression patterns suggest a role for shh signaling in the secretion and patterning of the regenerating dermal bone, but a direct role has not been demonstrated. We established an in vivo method of gene transfection to express ectopically genes in the blastema of regenerating fins. Ectopic expression of shh or bmp2 in the blastema-induced excess bone deposition and altered patterning of the regenerate. The effects of shh ectopic expression could be antagonized by ectopic expression of chordin, an inhibitor of bone morphogenetic protein (bmp) signaling. We disrupted shh signaling in the regenerating fin by exposure to cyclopamine and found a dose-dependent inhibition of fin outgrowth, accumulation of melanocytes in the distal region of each fin ray, loss of actinotrichia, and reduction in cell proliferation in the mesenchyme. Morphological changes were accompanied by an expansion, followed by a reduction, in domains of shh expression and a rapid abolition of ptc1 expression. These results implicate shh and bmp2b signaling in the proliferation and/or differentiation of specialized bone-secreting cells in the blastema and suggest shh expression may be controlled by regulatory feedback mechanisms that define the region of bone secretion in the outgrowing fin.     

Characterization of two hepatitis B virus populations isolated from a hepatitis B surface antigen-negative patient

In a study of surface antigen-negative, but weakly hepatitis B virus (HBV) DNA-positive, patients, we were able to amplify and clone whole HBV genomes from the serum of a cirrhotic patient. Sequencing showed that the patient harbored two different HBV populations, one of genotype A and the other of genotype D, with the genotype D genome apparently predominating. The surface antigen of the genotype A virus is heavily mutated, especially in the extracellular < determinant a > region, with several mutations that have not been previously described. The genotype D virus is a precore mutant. Both genomes possess the common A1762T-G1764A double mutation of the basal core promoter (BCP), and the genotype D virus is also mutated in the < TATA box > of the large surface antigen promoter. Biological characterization showed that the genotype A genome was fully replication-competent, whereas the genotype D genome replicated poorly. The small surface antigen of the genotype A virus was only very weakly recognized by commercial tests. The small surface antigen of the genotype D virus could be recognized by the tests, but it was mainly retained within transfected cells, probably because of an excess of large surface antigen. In conclusion, the cryptic nature of this double HBV infection is characterized by the predominance of the replication-deficient genotype D virus over the replication-competent genotype A virus.     

Increased body iron stores in elite road cyclists

BACKGROUND: One third of French elite road cyclists were found to have hyperferritinemia on antidoping control tests performed during the Tour de France in 1998. PURPOSE: This study was undertaken to determine whether hyperferritinemia corresponded to elevated body iron stores or not and, affirmatively, what were its mechanism, its clinical consequences, and its spontaneous course. METHODS: 83 elite road male cyclists presenting with hyperferritinemia, defined as serum ferritin level greater than 300 microg.L-1, were studied with respect to consumption of iron and other drugs, serum iron tests, HFE mutations, and hepatic iron concentration (HIC; N < 35 micromol.g-1 dry weight). RESULTS: All cyclists were asymptomatic and had normal physical and cardiac examination. Their median (range) serum ferritin, serum iron, and transferrin saturation levels were 504 microg.L-1 (306-1671), 20 micromol.L-1 (8.5-36.3), and 39% (20-76), respectively. HIC was increased in 24/27 up to 187 micromol.g-1. Allelic frequency of the H63D mutation was increased in cyclists when compared to controls (P = 0.04). However, iron tests did not differ according to HFE genotypes. Most cyclists (89%) had been supplemented with iron. The median iron supplementation was 25.5 g (range: 1.4-336) and correlated well (P = 0.002) with serum ferritin. Evolution of serum ferritin levels did not differ whether cyclists had been continuing iron supplementation or not. CONCLUSION: Hyperferritinemia in elite road cyclists accounted for increased body iron stores caused by and persisting after cessation of excessive iron supplementation. Even when mild, iron excess may expose to long-term complications and should be removed, at least at the time when professional cyclists retire. To prevent iatrogenic iron overload, supplementation with iron must be done according to serum ferritin follow-up and not either blindly or on the basis of serum iron determination only.