Cerebral metabolic alterations in human immunodeficiency virus-related encephalopathy detected by proton magnetic resonance spectroscopy. Comparison between sequences using short and long echo times

RATIONALE AND OBJECTIVES: The aim of this study is to evaluate comparatively the metabolic information afforded by proton magnetic resonance (MR) spectroscopy with stimulated-echo acquisition mode (STEAM) (echo time [TE], 20 mseconds) and point-resolved spectroscopy sequence (PRESS) (TE, 135 mseconds) spectra in HIV-related encephalopathy. METHODS: Sixty-three human immunodeficiency virus (HIV) patients and 8 controls were examined by single-voxel proton MR spectroscopy at 1.5 tesla, using both PRESS (TE, 135 mseconds) and STEAM (TE, 20 mseconds) sequences performed during the same MR examination, in the same volume of interest. Cerebral atrophy was quantitated using bicaudate ratio (BCR) and bifrontal ratio (BFR). RESULTS: With the STEAM (TE, 20 mseconds) spectra, mean N-acetylaspartate (NAA)/choline (Cho) and NAA/creatine and phosphocreatine (Cr-PCr) ratios are reduced in acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) patients but not in neuroasymptomatics. The proportion of inositol signal is increased, that of NAA decreased in ADC patients. NAA/Cho and NAA/ Cr-PCr mean values measured with PRESS (TE, 135 mseconds) spectra are significantly reduced in ADC and neuroasymptomatic patients. Bifrontal ratio only correlates with NAA/Cr-PCr and NAA/Cho measured on the PRESS spectrum. PRESS (TE, 135 mseconds) spectra allow a definition of different metabolic patterns in HIV-related encephalopathy. At last, no correlation has been found between the NAA raw signals measured on the PRESS (TE, 135 mseconds) and STEAM (TE, 20 mseconds) spectra obtained in the same MR examination. CONCLUSIONS: STEAM (TE, 20 mseconds) spectra provide more metabolic information-namely an evaluation of glial-neuronal status-than PRESS (TE, 135 mseconds) spectra, which afford a metabolic classification of the HIV-related encephalopathy. Because both sequences afford a similar diagnostic gain, MR spectroscopy examination probably requires spectrum acquisition with both sequences.     

Formalizing Calendars with the Category of Ordinals

Starting from the basic notion of chronology, we provide a natural representation of calendars and appropriate tools for manipulating them, inside the framework of finite ordinals category. We show that calendars are closed under infimum and supremum operations but not under direct limits.     

Treatment of Mouse Sperm with a Non-Catalytic Mutant of PLA2G10 Reveals That PLA2G10 Improves In Vitro Fertilization through Both Its Enzymatic Activity and as Ligand of PLA2R1

The group X secreted phospholipase A2 (PLA2G10) is present at high levels in mouse sperm acrosome. The enzyme is secreted during capacitation and amplifies the acrosome reaction and its own secretion via an autocrine loop. PLA2G10 also improves the rate of fertilization. In in vitro fertilization (IVF) experiments, sperm from Pla2g10-deficient mice produces fewer two-cell embryos, and the absence of PLA2G10 is rescued by adding recombinant enzymes. Moreover, wild-type (WT) sperm treated with recombinant PLA2G10 produces more two-cell embryos. The effects of PLA2G10 on mouse fertility are inhibited by sPLA₂ inhibitors and rescued by products of the enzymatic reaction such as free fatty acids, suggesting a role of catalytic activity. However, PLA2G10 also binds to mouse PLA2R1, which may play a role in fertility. To determine the relative contribution of enzymatic activity and PLA2R1 binding in the profertility effect of PLA2G10, we tested H48Q-PLA2G10, a catalytically-inactive mutant of PLA2G10 with low enzymatic activity but high binding properties to PLA2R1. Its effect was tested in various mouse strains, including Pla2r1-deficient mice. H48Q-PLA2G10 did not trigger the acrosome reaction but was as potent as WT-PLA2G10 to improve IVF in inbred C57Bl/6 mice; however, this was not the case in OF1 outbred mice. Using gametes from these mouse strains, the effect of H48Q-PLA2G10 appeared dependent on both spermatozoa and oocytes. Moreover, sperm from C57Bl/6 Pla2r1-deficient mice were less fertile and lowered the profertility effects of H48Q-PLA2G10, which were completely suppressed when sperm and oocytes were collected from Pla2r1-deficient mice. Conversely, the effect of WT-PLA2G10 was not or less sensitive to the absence of PLA2R1, suggesting that the effect of PLA2G10 is polymodal and complex, acting both as an enzyme and a ligand of PLA2R1. This study shows that the action of PLA2G10 on gametes is complex and can simultaneously activate the catalytic pathway and the PLA2R1-dependent receptor pathway. This work also shows for the first time that PLA2G10 binding to gametes’ PLA2R1 participates in fertilization optimization.     

Poly(vinyl chloroformate) and its derivatives: 5. New poly(vinyl carbamates) and poly(vinyl thiocarbonates)

New poly(vinyl carbamates) and poly(vinyl thiocarbonates) have been prepared either by free radical polymerization of monomers or by chemical modification of poly(vinyl chloroformate) with appropriate amines and thiols using phase transfer catalysis. The structure of these polymers has been examined by i.r. and ¹³C n.m.r. spectroscopy and their thermal behaviour has been studied.     

Anionic polymerization of isoprene by the complexes oligoisoprenyllithium/tertiary polyamines in cyclohexane: 3. Structural study of the polymers by 1H n.m.r. at 100 MHz

The microstructure of polyisoprene prepared anionically in the presence of catalytic amounts of N,N,N′,N′-tetramethylethylenediamine (TMEDA) and pentamethyldiethylenetriamine (PMDT) has been studied as a function of $\text{r =}\text{[}\text{TMEDA}\text{]}\text{[}\text{living ends}\text{]}$ and $\text{r =}\text{[}\text{PMDT}\text{]}\text{[}\text{living ends}\text{]}$. No significant effect is observed for r ? 0.5. The structure varies drastically for r > 0.5. The 4,3 addition increases mainly at the expense of the cis4,1 addition and a plateau is reached for r ? 1.0. The results are discussed on the basis of the nature of the living species.     

Analysis of aged gelatin by AFlFFF-MALS: Identification of high molar mass components and their influence on solubility

Gelatin is an important product for several industries and its solubility dramatically influences its functional properties. In order to be able to predict the gelatin behaviour, a new technique for its analysis has been developed with an Asymmetrical Flow Field-Flow Fractionation coupled to a multi-angle light scattering. The AFlFFF-MALS analysis showed the gelatin molar mass ranging from 5 × 10⁴ to 2 × 10⁷ g mol⁻¹. This technique also permitted to follow aggregation of gelatin samples after process in an oven at 75 °C. Between 0 and 4 days, some huge aggregates appeared. Their size and density increased without changing gelatin solubility. From 8 to 30 days, the molar mass and density of these aggregates increased leading to partial gelatin insolubilisation in water. This phenomenon is supposed to be due to cross-linking of the gelatin macromolecules.     

Superparamagnetic Liposomes for MRI Monitoring and External Magnetic Field‐Induced Selective Targeting of Malignant Brain Tumors

Magnetic‐fluid‐loadedliposomes (MFLs) of optimized magnetic responsiveness are newly worked out from the entrapment of superparamagnetic maghemite nanocrystals in submicronic PEG‐ylated rhodamine‐labelled phospholipid vesicles. This nanoplatform provides an efficient tool for the selective magnetic targeting of malignant tumors localized in brain and non‐invasive traceability by MRI through intravascular administration. As assessed by in vivo 7‐T MRI and ex vivo electron spin resonance, 4‐h exposure to 190‐T m^–1 magnetic field gradient efficiently concentrates MFLs into human U87 glioblastoma implanted in the striatum of mice. The magnetoliposomes are then longer retained therein as checked by MRI monitoring over a 24‐h period. Histological analysis by confocal fluorescence microscopy confirms the significantly boosted accumulation of MFLs in the malignant tissue up to the intracellular level. Electron transmission microscopy reveals effective internalization by endothelial and glioblastoma cells of the magnetically conveyed MFLs as preserved vesicle structures. The magnetic field gradient emphasizes MFL distribution solely in the tumors according to the enhanced permeability and retention (EPR) effect while comparatively very low amounts are recovered in the other cerebral areas. Such a selective targeting precisely traceable by MRI is promising for therapeutic applications since the healthy brain tissue can be expected to be spared during treatments by deleterious anticancer drugs carried by magnetically guided MFLs.     

Silane Deuteration Catalyzed by Ruthenium Bis(dihydrogen) Complexes or Simple Metal Salts

The deuteration of a diverse group of silanes: alkyl‐, aryl‐, alkoxy‐ and chlorosilanes, siloxane and silazane, under an atmosphere of dideuterium (D₂) was explored with ruthenium bis(dihydrogen) dihydride complexes and hydrated metal salts. Deuterium incorporation of greater than 97% for the silanes O(SiMe₂H)₂, Et₃SiH, (EtO)₃SiH and Me₂ClSiH was possible with 0.1 mol% of the ruthenium complex [RuH₂(η²‐H₂)₂(PCyp₃)₂] [0.05 mol% for O(SiMe₂H)₂] when catalysis was conducted in the neat silane at 30 °C under 1 bar of D₂ for 3.5 h. The air‐stable ruthenium trichloride salt RuCl₃⋅x H₂O was also an efficient catalyst for the deuteration of O(SiMe₂H)₂ and Et₃SiH; deuterium incorporations for the two silanes of 93% and 90%, respectively, were possible under the same conditions as for [RuH₂(η²‐H₂)₂(PCyp₃)₂] with 0.1% catalyst loading. Hydrogen–deuterium exchange of O(SiMe₂H)₂ catalyzed by the rhodium trichloride (RhCl₃⋅x H₂O) and iridium trichloride (IrCl₃⋅x H₂O) was similarly efficient as with RuCl₃⋅x H₂O although catalytic alacrity dropped for Et₃SiH.