Toxicology and carcinogenesis studies of a nondecolorized [corrected] whole leaf extract of Aloe barbadensis Miller (Aloe vera) in F344/N rats and B6C3F1 mice (drinking water study).

BACKGROUND: Extracts from the leaves of the Aloe vera plant (Aloe barbadensis Miller) have long been used as herbal remedies and are also now promoted as a dietary supplement, in liquid tonics, powders or tablets, as a laxative and to prevent a variety of illnesses. We studied the effects of Aloe vera extract on rats and mice to identify potential toxic or cancer-related hazards. METHODS: We gave solutions of nondecolorized extracts of Aloe vera leaves in the drinking water to groups of rats and mice for 2 years. Groups of 48 rats received solutions containing 0.5%, 1% or 1.5% of Aloe vera extract in the drinking water, and groups of mice received solutions containing 1%, 2%, or 3% of Aloe vera extract. Similar groups of animals were given plain drinking water and served as the control groups. At the end of the study tissues from more than 40 sites were examined for every animal. RESULTS: In all groups of rats and mice receiving the Aloe vera extract, the rates of hyperplasia in the large intestine were markedly increased compared to the control animals. There were also increases in hyperplasia in the small intestine in rats receiving the Aloe vera extract, increases in hyperplasia of the stomach in male and female rats and female mice receiving the Aloe vera extract, and increases in hyperplasia of the mesenteric lymph nodes in male and female rats and male mice receiving the Aloe vera extract. In addition, cancers of the large intestine occurred in male and female rats given the Aloe vera extract, though none had been seen in the control groups of rats for this and other studies at this laboratory. CONCLUSIONS: We conclude that nondecolorized Aloe vera caused cancers of the large intestine in male and female rats and also caused hyperplasia of the large intestine, small intestine, stomach, and lymph nodes in male and female rats. Aloe vera extract also caused hyperplasia of the large intestine in male and female mice and hyperplasia of the mesenteric lymph node in male mice and hyperplasia of the stomach in female mice.

Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors.

Vagus nerve stimulation (VNS) is an FDA approved treatment for drug-resistant epilepsy and depression. Recently, we demonstrated the capacity for repeatedly pairing sensory input with brief pulses of VNS to induce input specific reorganization in rat auditory cortex. This was subsequently used to reverse the pathological neural and perceptual correlates of hearing loss induced tinnitus. Despite its therapeutic potential, VNS mechanisms of action remain speculative. In this study, we report the acute effects of VNS on intra-cortical synchrony, excitability, and sensory processing in anesthetized rat auditory cortex. VNS significantly increased and decorrelated spontaneous multi-unit activity, and suppressed entrainment to repetitive noise burst stimulation at 6-8 Hz but not after application of the muscarinic antagonist scopolamine. Collectively, these experiments demonstrate the capacity for VNS to acutely influence cortical synchrony and excitability and strengthen the hypothesis that acetylcholine and muscarinic receptors are involved in VNS mechanisms of action. These results are discussed with respect to their possible implications for sensory processing, neural plasticity, and epilepsy.

Muscarinic M2 and M1 receptors reduce GABA release by Ca2+ channel modulation through activation of PI3K/Ca2+ -independent and PLC/Ca2+ -dependent PKC.

We measured pharmacologically isolated GABAergic currents from layer II/III neurons of the rat auditory cortex using patch-clamp recording. Activation of muscarinic receptors by muscarine (1 microM) or oxotremorine (10 microM) decreased the amplitude of electrically evoked inhibitory postsynaptic currents to about one third of their control value. Neither miniature nor exogenously evoked GABAergic currents were altered by the presence of muscarinic agonists, indicating that the effect was spike-dependent and not mediated postsynaptically. The presence of the N- or P/Q-type Ca(2+) channel blockers omega-conotoxin GVIA (1 microM) or omega-AgaTx TK (200 nM) greatly blocked the muscarinic effect, suggesting that Ca(2+)-channels were target of the muscarinic modulation. The presence of the muscarinic M(2) receptor (M(2)R) antagonists methoctramine (5 muM) or AF-DX 116 (1 microM) blocked most of the muscarinic evoked inhibitory postsynaptic current (eIPSC) reduction, indicating that M(2)Rs were responsible for the effect, whereas the remaining component of the depression displayed M(1)R-like sensitivity. Tissue preincubation with the specific blockers of phosphatidyl-inositol-3-kinase (PI(3)K) wortmannin (200 nM), LY294002 (1 microM), or with the Ca(2+)-dependent PKC inhibitor Gö 6976 (200 nM) greatly impaired the muscarinic decrease of the eIPSC amplitude, whereas the remaining component was sensitive to preincubation in the phospholipase C blocker U73122 (10 microM). We conclude that acetylcholine release enhances the excitability of the auditory cortex by decreasing the release of GABA by inhibiting axonal V-dependent Ca(2+) channels, mostly through activation of presynaptic M(2)Rs/PI(3)K/Ca(2+)-independent PKC pathway and-to a smaller extent-by the activation of M(1)/PLC/Ca(2+)-dependent PKC.

Environmental enrichment selectively increases glutamatergic responses in layer II/III of the auditory cortex of the rat.

Prolonged exposure to environmental enrichment (EE) induces behavioral adaptation accompanied by detectable morphological and physiological changes. Auditory EE is associated with an increased auditory evoked potential (AEP) and increased auditory gating in the primary auditory cortex. We sought physiological correlates to such changes by comparing synaptic currents in control vs. EE-raised rats, in a primary auditory cortex (AI) slice preparation. Pharmacologically isolated glutamatergic or GABA(A)-receptor-mediated currents were measured using perforated patch whole-cell recordings. Glutamatergic AMPA receptor (AMPAR)-mediated excitatory postsynaptic currents (EPSCs) displayed a large amplitude increase (64+/-11% in EE vs. control) accompanied by a rise-time decrease (-29+/-6% in EE vs. control) and decrease in pair pulse ratio in layer II/III but not in layer V. Changes in glutamatergic signaling were not associated with changes in the ratio between N-methyl-D aspartate-receptor (NMDAR)-mediated vs. AMPAR-mediated components, in amplitude or pair pulse ratio of GABAergic transmission, or in passive neuronal properties. A realistic computational model was used for integrating in vivo and in vitro results, and for determining how EE synapses correct for phase error of the inputs. We found that EE not only increases the mean firing frequency of the responses, but also improves the robustness of auditory processing by decreasing the dependence of the output firing on the phase difference of the input signals. We conclude that behavioral and electrophysiological differences detected in vivo in rats exposed to an auditory EE are accompanied and possibly caused by selective changes in cortical excitatory transmission. Our data suggest that auditory EE selectively enhances excitatory glutamatergic synaptic transmission in layer II/III without greatly altering inhibitory GABAergic transmission.

Cyclin E and its associated cdk activity do not cycle during early embryogenesis of the sea Urchin.

Female sea urchins store their gametes as haploid eggs. The zygote enters S-phase 1 h after fertilization, initiating a series of cell cycles that lack gap phases. We have cloned cyclin E from the sea urchin Strongylocentrotus purpuratus. Cyclin E is synthesized during oogenesis, is present in the germinal vesicle, and is released into the egg cytoplasm at oocyte maturation. Cyclin E synthesis is activated at fertilization, although there is no increase in cyclin E protein levels due to continuous turnover of the protein. Cyclin E protein levels decline in morula embryos, while cyclin E mRNA levels remain high. After the blastula stage, cyclin E mRNA and protein levels are very low, and cyclin E expression is predominant only in cells that are actively dividing. These include cells in the left coelomic pouch, which forms the adult rudiment in the embryo. The cyclin E present in the egg is complexed with a protein kinase. Activity of the cyclin E/cdk2 changes little during the initial cell cycles. In particular, cyclin E-cdk2 levels remain high during both S-phase and mitosis. Our results suggest that progression through the early embryonic cell cycles in the sea urchin does not require fluctuations in cyclin E kinase activity.

Control of column temperature in reversed-phase liquid chromatography.

When separations by reversed-phase liquid chromatography (RP-LC) are carried out at temperatures other than ambient, resulting retention times and bandwidths can depend on the equipment used. As a result, an RP-LC separation that is adequate when carried out on one LC system may prove inadequate when the separation is repeated on a second system. In the present study, various temperature-related problems which can result in a failure of method transfer for non-ambient RP-LC methods were examined. Means for correcting for such effects and thereby ensuring method transferability are described.

Performance of experimental sample injectors for high-performance liquid chromatography microcolumns.

An experimental injector for HPLC microcolumns and a 3-nl conductivity detector connected directly to the injector outlet with a 19-nl tube were used to study injector dispersion, guide the design of improved injectors, and suggest appropriate injection techniques. With regard to the small injection volumes required when no on-column concentration technique is used, we show that in some circumstances: (i) there are two volumes to be considered, the sample volume (that which is intended to be injected) and the effective injection volume (that which contains all the sample after it has completely emerged from the injector). Due to dispersion, the latter is often many times the former. An injector performance factor is defined as the ratio of the two volumes. (ii) A smaller sample chamber volume in an injector does not necessarily produce a proportionately smaller effective injection volume, in which case there is a reduction of peak height that degrades sensitivity without a commensurate reduction in peak width that would improve resolution. (iii) Adjusting the geometry of the sample chamber and stator passage can significantly improve injector performance, as illustrated for sample volumes from 2 nl to 1 microl. (iv) In some cases, reducing the diameter of an injector passageway in an attempt to reduce dispersion actually causes performance to worsen.

Assessing anxiety about retirement: the case of academicians.

One hundred and forty-four individuals, ninety-two of whom were active university faculty and fifty-two of whom were retired, completed a measure of anxiety about retirement as well as a battery of self-report scales assessing a number of personality, job-related, and retirement-specific constructs. Results suggested that the newly developed measure of retirement anxiety possessed high internal consistency as well as both discriminant and construct validity. Moreover, it is multidimensional in nature, and distinct in content from previous scales assessing anxiety about retirement. Its use for persons anticipating retirement is discussed in the context of the benefits of a proactive stance toward retirement preparation.

Computer-assisted edge detection in two-dimensional echocardiography: comparison with anatomic data.

Four methods of computer-based edge detection were evaluated for identification of endocardial and epicardial borders on 2-dimensional echocardiograms of excised hearts. A method was also evaluated for observer identification of cardiac borders in the same hearts. The accuracy of computer-derived borders and of observer-derived borders were determined by comparison to anatomic borders measured from photographs of slices of the excised hearts. Echocardiographic borders were compared with anatomic borders by calculation of segmental cavity areas and wall thickness. Each of the methods tested (computer and observer) identified endocardial borders accurately, resulting in cavity segment areas that correlated well with the corresponding anatomic data (r = 0.90 to 0.92). Regional wall thicknesses correlated less well with anatomic data (r = 0.74 to 0.80), suggesting that endocardial borders were identified more accurately than were epicardial borders. Thus, the methods of computer-assisted echocardiographic border detection tested identified the endocardium and epicardium as accurately as a trained observer evaluating unprocessed echocardiograms. Computer-based methods of border detection may be useful in the automated analysis of clinical echocardiograms.

An accurate data collection method for spatial motion using a sonic digitizer.

An accurate collecting method for spatial displacement data utilizing a sonic digitizer which works electronically and acoustically is described. The sequence of the operation of the digitizer system is explained. As an application, the study of elbow flexion-extension is presented. Finally, operational precautions for using this system are discussed.

Revaccination against measles--a pilot study.

(1) During the first ten years after primary vaccination with live measles virus vaccine, a slow decline in the level of HAI antibody titres has been demonstrated. The decline after more attenuated vaccines was at the same gradient, but at lower titres.(2) During the same period after primary vaccination by inactivated (; killed ') followed by live - K + L - measles vaccine, a much steeper decline in the level of HAI antibody titres was demonstrated.(3) The GMT may not reach the lowest standard titres for over 40 years after the least attenuated vaccine, and 20-25 years after more attenuated vaccines. After K + L vaccine the GMT may be negative after 15 years or less, but this will depend on the frequency of natural boosting.(4) On revaccination after five to ten years, one out of 20 children (five per cent) who had received live vaccine alone for primary vaccination showed a fourfold or greater rise in titre of HAI antibody, whereas 17 out of 41 children (41%) who had received K + L vaccine showed a significant rise in titre.(5) With either regime, the age at primary vaccination did not appear to influence the rate of boosting after revaccination except perhaps in children under two years.(6) Among those who originally received K + L Vaccine, The Lower The Hai Antibody Titre Before Revaccination And The Longer The Time Since Primary Vaccination, The More Likely Was A Significant Rise In Titre To Occur After Revaccination. All Should Be Revaccinated Within 10-15 Years Of Primary Immunisation.(7) Children whose primary vaccination was by live ;further attenuated' vaccine before the age of two years may need to be revaccinated before they leave school, but this requires further study.(8) A case can be made for using a less attenuated strain of measles virus for revaccination than for primary vaccination.(9) The eventual need for and timing of revaccination against measles should be examined in a larger group of children.