Brain proton magnetic resonance spectroscopy (1H-MRS) in Alzheimer's disease: changes after treatment with xanomeline, an M1 selective cholinergic agonist

OBJECTIVE: Higher than normal cellular levels of the phospholipid catabolic intermediate glycerophosphocholine have been found in postmortem brain tissue of persons with Alzheimer's disease. Proton magnetic resonance spectroscopy (1H-MRS) can detect a choline resonance that is largely due to glycerophosphocholine. The authors tested the hypothesis that treatment with xanomeline, an M1 selective muscarinic cholinergic agonist, would be associated with a decrease in the 1H-MRS choline resonance. METHOD: Patients with mild to moderate Alzheimer's disease received placebo or xanomeline for 6 months. 1H-MRS spectra were collected at baseline and after treatment discontinuation for 12 patients, two taking placebo and 10 taking xanomeline at a dose of 25 mg t.i.d. (N = 4), 50 mg t.i.d. (N = 3), or 75 mg t.i.d. (N = 3). RESULTS: For the combined group of patients taking xanomeline, there was a significant decrease in the choline/creatine ratio from baseline to endpoint. CONCLUSIONS: Treatment of Alzheimer's disease with a cholinergic agonist is associated with a decrease in the MRS choline resonance. Xanomeline may reduce breakdown of cholinergic neuron membranes by reducing the cellular requirement for free choline for acetylcholine synthesis.     

Production constraints on utterance-final consonant characteristics in babbling

In order to evaluate hypotheses regarding production constraints on final consonants in babbling, 721 utterance-final consonants produced by 6 infants in consonant-vowel-consonant (CVC) syllables were examined and compared with the preceding consonant in the CVC. Consistent with earlier studies, major patterns were observed for each of the three main consonantal properties--place and manner of articulation and voicing. These patterns included a strong tendency for final consonants to repeat the place of articulation of nonfinal consonants and a tendency for relatively more fricative, nasal and voiceless consonants to occur in final position than in nonfinal position. The high frequency with which final consonants shared place of articulation with the preceding consonant was considered to reflect 'frame dominance' or the tendency of a relatively constant mandibular cycle (the frame) to determine the structure of utterances with very little contribution from other active articulators. The manner and voicing effects were attributed to an overall terminal energy decrease in the vocal production system.     

Fourier Transform Infrared Emission Spectroscopy of the C4Delta-X4Phi, G4Phi-X4Phi, and G4Phi-C4Delta Systems of TiCl

The emission spectrum of TiCl has been investigated in the 3000-12 000 cm-1 region at high resolution using a Fourier transform spectrometer. The bands were excited in a microwave discharge through a flowing mixture of TiCl4 and helium. The observed bands have been classified into three electronic transitions, C4Delta-X4Phi, G4Phi-X4Phi, and G4Phi-C4Delta. In the 3000-3500 cm-1 region, four bands with R heads at 3368.7, 3331.8, 3291.9, and 3243.4 cm-1 have been assigned as the 0-0 bands of the 1/2-3/2, 3/2-5/2, 5/2-7/2, and 7/2-9/2 subbands, respectively, of the C4Delta-X4Phi transition. To higher wavenumbers, four transitions with 0-0 R heads at 10 930.7, 10 921.3, 10 906.5, and 10 886.9 cm-1 have been assigned as the 3/2-3/2, 5/2-5/2, 7/2-7/2, and 9/2-9/2 subbands, respectively, of the G4Phi-X4Phi system of TiCl. Four additional bands with 0-0 R heads at 7568.8, 7596.4, 7622.2, and 7651.7 cm-1 have been identified as the 1/2-3/2, 3/2-5/2, 5/2-7/2, and 7/2-9/2 subbands of the G4Phi-C4Delta transition, respectively. A rotational analysis of a number of vibrational bands of these transitions has been obtained and molecular constants have been extracted. The lowest 4Phi state has been assigned as the ground state of TiCl, by analogy with our recent work on TiF (R. S. Ram and P. F. Bernath, J. Mol. Spectrosc., in press). The correspondence between the electronic states of TiCl, TiF, TiH, and Ti+ is also discussed. Copyright 1997 Academic Press. Copyright 1997Academic Press     

Accuracy of formulae for calculating left ventricular volumes of the equine heart

Echocardiography may be an accurate method of measuring left ventricular (LV) volumes and mass of the horse's heart. If so, studies of the heart size and hypertrophy would be possible. This study evaluated geometric models of the external and internal LV shapes, to determine which could be applied to echocardiographic measurements. We preserved 30 horses' hearts and measured their dimensions and cross sectional areas. These measurements were entered into seven formulae representing different geometric models of the ventricle and its chamber. We derived a correction factor to estimate the long axis as a fixed proportion of the external diameter, so that volumes could be determined from an M-mode or a cross sectional echocardiogram. Statistical analysis of the regressions of known volumes against calculated volumes measured by water displacement, demonstrated that the ellipsoid formula using cross sectional areas was very accurate in representing the external shape of the left ventricle (slope = 1.01 r2 = 96.3) and its chamber (slope = 0.83, r2 = 94.3). Myocardial volume, measured by subtracting internal (chamber) volume from external volume, was also calculated accurately (slope = 1.01, r2 = 96.5). The ellipsoid formula using directly measured diameter was only slightly less accurate. LV mass could be calculated by applying the specific gravity of equine myocardium, 1.05, to the myocardial volume. Formulae recommended for evaluating are, with M-mode echocardiography: [equation: see text] and with 2D echocardiography [equation: see text] where De is the external diameter, Di is the internal diameter, Ae the external area and Ai the internal area.     

Compensation for decreased expression of B7 molecules on Leishmania infantum-infected canine macrophages results in restoration of parasite-specific T-cell proliferation and gamma interferon production

Infection of humans and dogs by Leishmania infantum may result in visceral leishmaniasis, which is characterized by impaired T-cell-mediated immune responses to parasite antigens. Dogs are natural hosts of Leishmania parasites and play an important role in the transmission of the parasites to humans. In an effort to characterize the immune response in dogs infected with this intracellular pathogen, we examined how infection with L. infantum affects canine macrophages and the consequences for T-cell activation in vitro. We showed that the proliferation of T-cell lines to cognate antigen decreases to background levels when infected autologous monocyte-derived macrophages are used as antigen-presenting cells (APC). The observed reduction of antigen-specific T-cell proliferation was shown to be dependent on the parasite load and to require cell-to-cell interaction of T cells with the infected APC. In addition, we observed a decreased expression of costimulatory B7 molecules on infected monocyte-derived macrophages. The expression of other surface molecules involved in T-cell activation, such as major histocompatibility complex class I and class II, on these cells did not change upon infection, whereas the expression of intracellular adhesion molecule 1 was marginally increased. Compensation for the decreased expression of B7 molecules by the addition of B7-transfected cells resulted in the restoration of cell proliferation and gamma interferon (IFN-gamma) production by a Leishmania-specific T-cell line. These results showed that for the activation of parasite-specific canine T cells producing IFN-gamma, which are most likely involved in protective immunity, sufficient expression of B7 molecules on infected macrophages is required. Provision of costimulatory molecules may be an approach for immunotherapy of leishmaniaisis as well as for vaccine development.     

Corporate Water Footprint Accounting and Impact Assessment: The Case of the Water Footprint of a Sugar-Containing Carbonated Beverage

All water use in the world is ultimately linked to final consumption by consumers. It is therefore interesting to know the specific water requirements of various consumer goods, particularly the water-intensive ones. This information is relevant not only for consumers, but also for food processors, retailers, and traders. The objective of this paper is to carry out a pilot study on water footprint accounting and impact assessment for a hypothetical sugar-containing carbonated beverage in a 0.5 l PET-bottle produced in a hypothetical factory that takes its sugar alternatively from sugar beet, sugar cane and high fructose maize syrup and from different countries. The composition of the beverage and the characteristics of the factory are hypothetical but realistic. The data assumed have been inspired by a real case. This paper does not only look at the water footprint of the ingredients of the beverage, but also at the water footprint of the bottle, other packaging materials and construction materials, paper and energy used in the factory. Although most companies focus on their own operational performance, this paper shows that it is important to consider freshwater usage along the supply chain. The water footprint of the beverage studied has a water footprint of 150 to 300 l of water per 0.5 l bottle, of which 99.7–99.8% refers to the supply chain. The study also shows that agricultural ingredients that constitute only a small fraction in weight of the final product have the biggest share at the total water footprint of a product.