神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

Spatial frequency content of the Cardiff and related acuity tests

In the Cardiff acuity test, simple pictures on an otherwise neutral grey card are defined by borders consisting of a relatively broad white band flanked by black bands each half the width of the white band. Higher levels of acuity correspond to the ability to detect figures defined by narrower borders, the figure size remaining constant. It is sometimes implied that the acuity limit corresponding to each card can be equated with different levels of grating resolution, the total width of the border corresponding to the overall grating period. It is shown that although the spatial frequency spectra of the Cardiff figures, like those of other vanishing optotypes, lack very low-frequency components, they have a complex two-dimensional form. The figures have wide spatial bandwidth and no well-defined discrete frequency components. As a result, the relationship between measured Cardiff and grating acuity will vary somewhat, depending upon the particular optical, neural or other deficits of the individual being tested.     

A novel cubic phase of medium chain lipid origin for the delivery of poorly water soluble drugs.

The existence of a novel cubic liquid crystalline phase is described within the pseudo-ternary system comprising lauric acid, monolaurin, and simulated endogenous intestinal fluid (SEIF). This phase behaviour has been characterized using cross-polarizing light microscopy (CPLM), and the structure of the cubic phase identified by small angle X-ray scattering (SAXS). The presence of the cubic phase was found to be temperature sensitive within the 20-37 degrees C range making it putative material for in situ gelation purposes. The cubic phase was shown to have a high capacity to solubilise a model poorly water-soluble drug, cinnarizine, and initial in vitro release data highlight the potential of this phase to provide sustained release. Absorption of cinnarizine from the cubic phase was studied in an unconscious rat model via duodenal administration and blood sampling via the carotid artery. The rate of absorption was significantly reduced when compared to a simple suspension formulation, a likely combination of retarded erosion of the cubic phase together with hindered drug release from the cubic matrix. The results of this study suggest that this cubic phase may potentially be of benefit in the delivery of poorly water-soluble compounds due to its high loading capacity and potential for sustained release. The ability to manipulate this system using temperature may warrant further interest in delivery applications via other routes of administration.     

Behaviour problems in adult women with Rett syndrome

Background Despite considerable interest in the genetic, physical and neurological aspects of Rett syndrome (RS), there have been few studies of associated behavioural and emotional features. Furthermore, few case studiesor surveys have included adult women with RS. The main aim of the present study was to compare behaviour problems in a sample of women with RS against data from normative samples. Methods The primary carers of 50 women with RS completed the community version of the Aberrant Behavior Checklist. Results Women with RS were rated as having lower levels of irritability, hyperactivity and inappropriate speech behaviours than normative samples of adults with intellectual disability. Conclusions A number of factors may affect the presentation of behaviour problems in women with RS (e.g. cognitive impairments or physical disabilities). Therefore, more research is needed in order to generate information about the behavioural phenotype of RS. The implications of the present data for future research are also discussed.     

Evaluation of the mass balance assumption with respect to the two-resistance model of intestinal absorption by using in situ single-pass intestinal perfusion of theophylline in rats.

Methods of analyzing drug absorption data from rat intestinal-perfusion experiments are discussed in terms of mass-transfer resistances, or reciprocal permeabilities, and mass balances. Typically, a two-resistance model is used to determine the dimensionless effective permeability (P*eff) by measuring the disappearance of drug from the perfusing solution. Unstated assumptions in two-resistance models are (1) the portal blood is under sink conditions and (2) complete transfer of drug occurs from the intestinal perfusate to the portal vein. The assumption of sink conditions is generally acceptable, because the drug concentration in portal blood is approximately two orders of magnitude less than in the perfusate. Single-pass intestinal-perfusion experiments were performed on rats with theophylline as a model compound. The drug mass leaving the intestinal perfusate was substantially less than the drug mass appearing in the portal plasma; that is, the assumption of complete transfer did not hold for theophylline in this experimental system. These data indicate that models based on the two-resistance theory can lead to overestimation of P*eff by the ratio of the drug mass leaving the perfusate to the drug mass appearing in the plasma. For compounds for which the assumption of complete transfer does not hold, a more accurate estimate of P*eff may be determined by dividing the value derived from perfusate data by the mass balance ratio (i.e., the drug mass leaving the perfusate divided by the drug mass appearing in the plasma).     

Age, lens transmittance, and the possible effects of light on melatonin suppression

Recently it has been suggested that a previously undetected, rhodopsin-based, visual pigment, located in some retinal ganglion cells and having a peak sensitivity around 460 nm, may be responsible for light-induced melatonin suppression and, perhaps, maintenance of the circadian rhythm. Using data from the literature, it is shown that, as absorption in the crystalline lens for shorter visible wavelengths increases substantially with age, while the pupil diameter tends to decrease, the effective retinal exposure received under the same ambient lighting conditions by the pigment is almost 10 times lower in an old, as compared with a young, eye. Interestingly, replacement of the old crystalline lens by an intraocular implant restores the exposure to youthful levels. The possible effects of these changes with age on circadian rhythms are discussed.     

Accommodation responses and ageing.

PURPOSE: To study the impact of age on accommodation dynamics. METHODS: Monocular accommodation responses were measured continuously using a modified Canon Auto Ref R1 infrared optometer. The stimulus was a single letter oscillating sinusoidally between 2.38 and 1.33 D providing a stimulus amplitude of 0.52 D, about a mean level of 1.86 D. Response characteristics were used to quantify gain and phase. Step responses were also recorded between these stimulus vergence levels for calibration purposes and to measure reaction and response times. Nineteen visually normal subjects 18 to 49 years of age participated, and 11 frequencies were used in the range 0.05 to 1.0 Hz. A key feature of the experimental design was to use a stimulus vergence range that lay within the amplitude of accommodation of all the observers. RESULTS: Accommodation gain reduced and phase lag increased with age, particularly at the higher frequencies used. No strongly significant change with age was found for reaction and response times or accommodation velocity, and results were similar for both far-to-near and near-to-far responses. Response amplitude for the step change in target vergence declined with age, and substantial differences were found between the measured and predicted (from reaction time) phase lags at 1.0 Hz as a function of age. Young observers showed a phase lag that was shorter than predicted, whereas older observers' measured phase lags were considerably larger than predicted. CONCLUSIONS: Results show that for a target oscillating sinusoidally in a predictable manner at a modest amplitude, the main ageing effects occur in phase lag, which is appreciably longer than predicted from reaction times in the older observers. The effects of ageing on gain were not as marked. Although responses to small step changes do reduce with age, there is no evidence of increased response times with ageing. In general, accommodation function in the middle-aged eye is quite robust despite a dwindling amplitude of accommodation. These results provide evidence of accommodative vigor in youth and a slowing of accommodation with ageing.