Obstructive sleep apnea,immuno-inflammation,and atherosclerosis

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder leading to cardiovascular and metabolic complications. OSA is also a multicomponent disorder, with intermittent hypoxia (IH) as the main trigger for the associated cardiovascular and metabolic alterations. Indeed, recurrent pharyngeal collapses during sleep lead to repetitive sequences of hypoxia–reoxygenation. This IH induces several consequences such as hemodynamic, hormonometabolic, oxidative, and immuno-inflammatory alterations that may interact and aggravate each other, resulting in artery changes, from adaptive to degenerative atherosclerotic remodeling. Atherosclerosis has been found in OSA patients free of other cardiovascular risk factors and is related to the severity of nocturnal hypoxia. Early stages of artery alteration, including functional and structural changes, have been evidenced in both OSA patients and rodents experimentally exposed to IH. Impaired vasoreactivity with endothelial dysfunction and/or increased vasoconstrictive responses due to sympathetic, endothelin, and renin–angiotensin systems have been reported and also contribute to vascular remodeling and inflammation. Oxidative stress, inflammation, and vascular remodeling can be directly triggered by IH, further aggravated by the OSA-associated hormonometabolic alterations, such as insulin resistance, dyslipidemia, and adipokine imbalance. As shown in OSA patients and in the animal model, genetic susceptibility, comorbidities (obesity), and life habits (high fat diet) may aggravate atherosclerosis development or progression. The intimate molecular mechanisms are still largely unknown, and their understanding may contribute to delineate new targets for prevention strategies and/or development of new treatment of OSA-related atherosclerosis, especially in patients at risk for cardiovascular disease.     

Morphologic changes and altered gene expression in an epithelioid hemangioendothelioma during a ten-year course of disease

Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant vascular neoplasm with unpredictable prognosis. We report on a patient suffering from a vascular neoplasm with primary manifestation in the skeleton and subsequent development of lesions of EHE in the spleen, liver and lung. Based on the assumption that involvement of visceral organs was due to metastatic spread, changes in clinical behavior, morphology, and proliferation index suggest malignant progression of the tumor. Analyzing the expression of genes known to be involved in the pathogenesis of vascular tumors, we found that the appearance of less differentiated tumor was paralleled by an accumulation of TP53 and murine double minute-2 (MDM-2) protein, decreased caveolin-1 (CAV-1) expression, and increased vascular endothelial growth factor (VEGF) expression. Mutations of the von-Hippel-Lindau-tumor-suppressor-gene (VHL) were excluded as mechanism of VEGF upregulation. Therefore, we propose that the expression of TP53, MDM-2, CAV-1 and VEGF as a marker of biologic behavior be verified in a larger case study of EHE.     

Molecular epidemiology of Enterobacteriaceae isolates producing extended-spectrum beta-lactamases in a French hospital

In 2002, 80 isolates of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) were collected from infected patients in our hospital. Enterobacter aerogenes was the most common bacterium isolated from all specimens (36.5%). The ESBLs were predominantly (90%) TEM derivatives (TEM-24, TEM-3). Pulsed-field gel electrophoresis highlighted that E. aerogenes, Klebsiella pneumoniae, and Citrobacter koseri had a clonal propagation.     

Three-dimensional growth of differentiating MC3T3-E1 pre-osteoblasts on porous titanium scaffolds

The present work assesses the potential of three-dimensional porous titanium scaffolds produced by a novel powder metallurgy process for applications in bone engineering through in vitro experimentation. Mouse MC3T3-E1 pre-osteoblasts were used to investigate the proliferation (DNA content), differentiation (alkaline phosphatase activity and osteocalcin release) and mineralisation (calcium content) processes of cells on titanium scaffolds with average pore sizes ranging from 336 to 557 microm, using mirror-polished titanium as reference material. Scanning electron microscopy was employed to qualitatively corroborate the results. Cells proliferate on all materials before reaching a plateau at day 9, with proliferation rates being significantly higher on foams (ranging from 123 to 163 percent per day) than on the reference material (80% per day). Alkaline phosphatase activity is also significantly elevated on porous scaffolds following the proliferation stage. However, cells on polished titanium exhibit greater osteocalcin release toward the end of the differentiation process, resulting in earlier mineralisation of the extracellular matrix. Nevertheless, the calcium content is similar on all materials at the end of the experimental period. Average pore size of the porous structures does not have a major effect on cells as determined by the various analyses, affecting only the proliferation stage. Thus, the microstructured titanium scaffolds direct the behaviour of pre-osteoblasts toward a mature state capable of mineralising the extracellular matrix.     

Kaposi's sarcoma associated with previous human herpesvirus 8 infection in heart transplant recipients

The aim of this study was to evaluate the seroprevalence of human herpesvirus 8 (HHV-8) in a group of 150 patients awaiting heart transplants and to detect HHV-8 seroconversion after transplantation. Four patients were HHV-8 seropositive before transplantation, and one of them developed Kaposi's sarcoma. One patient converted to seropositive HHV-8 status after transplantation.     

Introduction into Cav2.1 of the homologous mutation of Cav1.2 causing the Timothy syndrome questions the role of V421 in the phenotypic definition of P-type Ca2+ channel

The Timothy syndrome is a multisystem disorder associated with the mutation of a Gly residue (G402 or G406) in the Ca_v1.2 Ca²⁺ channel. G406 is localized at the end of the IS6 segment and just before the intracellular I–II loop, which is important for the regulation of channel inactivation and the binding of the Ca_vβ subunit. This Gly residue is conserved in all Ca_v1 and Ca_v2 channels, and the G to R exchange produces a strong decrease of inactivation not only in Ca_v1.2 but also in Ca_v2.3. Here, we show that the mutation into Arg or Glu of the homologous Gly residue in Ca_v2.1 (G363) produces also a slowing of inactivation. However, the G-to-A exchange that decreases the inactivation rate in Ca_v1.2 and Ca_v2.3 increases inactivation in Ca_v2.1. Each mutation affects specifically the gating properties of Ca_v2.1 that remain nevertheless modulated by the co-expressed β subunit as with wild-type channel. The strong decrease of inactivation produced by the G363R or G363E mutations was reminiscent to that previously described for a specific splice variant of Ca_v2.1 that contains a single Val residue inserted in the I–II loop (V421). We unexpectedly found that the V421 insertion does not affect the inactivation rate of Ca_v2.1 and that the effects previously attributed to this insertion, including those on G-protein regulation, can be reproduced by the G363E mutation. Altogether, our results highlight the role of G363 in gating properties, inactivation kinetics, and G-protein regulation of Ca_v2.1 and the lack of effect of V421 insertion on inactivation. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Identification of dermatophytes by an oligonucleotide array

Species of dermatophytes are classified into three anamorphic (asexual) genera, Epidermophyton, Microsporum, and Trichophyton. Conventional methods used to identify dermatophytes are often lengthy and may be inconclusive because of atypical microscopic or colony morphology. Based on the internal transcribed spacer 1 (ITS-1) and ITS-2 sequences of the rRNA genes, an oligonucleotide array was developed to identify 17 dermatophyte species. The method consisted of PCR amplification of the ITS regions using universal primers, followed by hybridization of the digoxigenin-labeled PCR products to an array of oligonucleotides (17- to 30-mers) immobilized on a nylon membrane. Of 198 dermatophyte strains and 90 nontarget strains tested, the sensitivity and specificity of the array were 99.5% and 97.8%, respectively. The only strain not identified (Microsporum audouinii LMA 597) was found to have a nucleotide insertion at the ITS-2 region where the probe was designed. Two nontarget strains, Microsporum equinum LMA 40396666 and Trichophyton gourvilii var. intermedium CBS 170.65, were misidentified as Microsporum canis and Trichophyton soudanense, respectively. Sequence analysis of the ITS regions revealed that the two misidentified strains displayed high sequence homology with the probes designed for M. canis and T. soudanense, respectively. The present method can be used as a reliable alternative to conventional identification methods and can be completed with isolated colonies within 24 h.     

Arterial anatomical basis of the dorsal digito-metacarpal flap for long fingers

Several flaps have been described to treat severe soft tissue defects of the finger dorsal side. Many authors studied vascular organization of the hand on its dorsal side; most of them insisted on deep vascularization into the intermetacarpal spaces, which is formed by the dorsal metacarpal arteries. Those dorsal metacarpal arteries are the anatomical support of many flaps, which do not preserve the dorsal interosseous muscles fascias. Only few authors described dorsal vascular organization at the level of the proximal phalanx; however, using a rotation point of a flap distally to the metacarpal head with a donor site on the dorsal aspect of the hand could cover all distal soft tissue defect of long finger. In order to determine the technical limitations of dorsal digito-metacarpal flap procedures, we studied number and location of arterial anastomoses between the reticular subcutaneous dorsal network and the rest of the vascularization at this level, which was formed by the deeper dorsal metacarpal arteries, common palmar digital arteries and proper palmar digital arteries, and between the dorsal digital arteries. Twenty-four long fingers from embalmed cadavers were studied after a reverse flow injection of colored latex and dissected layer-by-layer preserving the digital-metacarpal arterial network. At the level of the hand, the dorsal metacarpal arteries of the third and fourth intermetacarpal spaces were inconstant. When present, two or three arteries anastomosed in star shape with the reticular network. No such arterial anastomosis was observed proximally to the level of the intertendinous connections (junctura tendinorum) that bridge the extensor digitorum communis tendons. When no dorsal metacarpal artery was present, some communicant arteries arose from the common palmar digital arteries. Moreover, all the nutrient branches were more numerous distally to the intertendinous connections (junctura tendinorum). At the level of the metacarpophalangeal joints, the hand cutaneous network was always anastomosed with the dorsal cutaneous network. At the level of fingers, the dorsal cutaneous network was always supplied by four branches arising from the proper digital artery. Our study supported the reliability of dorsal digitometacarpal flaps, supplied by numerous palmodorsal digital anastomoses and by a rich plexiforme network joining the hand skin supply and that of the dorsal finger skin. During the procedure, we recommend limiting the surgical dissection of the flap at the level of the middle phalanx.