Neural correlates of attentional expertise in long-term meditation practitioners.

Meditation refers to a family of mental training practices that are designed to familiarize the practitioner with specific types of mental processes. One of the most basic forms of meditation is concentration meditation, in which sustained attention is focused on an object such as a small visual stimulus or the breath. In age-matched participants, using functional MRI, we found that activation in a network of brain regions typically involved in sustained attention showed an inverted u-shaped curve in which expert meditators (EMs) with an average of 19,000 h of practice had more activation than novices, but EMs with an average of 44,000 h had less activation. In response to distracter sounds used to probe the meditation, EMs vs. novices had less brain activation in regions related to discursive thoughts and emotions and more activation in regions related to response inhibition and attention. Correlation with hours of practice suggests possible plasticity in these mechanisms.

Modulation of the multidrug-resistance phenotype by new tropane alkaloid aromatic esters from Erythroxylum pervillei.

Nine tropane alkaloid aromatic esters (1-9) were isolated from the roots of Erythroxylum pervillei by following their potential to reverse multidrug-resistance with vinblastine-resistant oral epidermoid carcinoma (KB-V1) cells. All isolates, including seven new structures (3-9), were evaluated against a panel of human cancer cell lines, and it was found that alkaloids 3 and 5-9 showed the greatest activity with KB-V1 cells assessed in the presence of vinblastine, suggesting that these new compounds are potent modulators of P-glycoprotein. Confirmatory results were obtained with human ovarian adenocarcinoma (SKVLB) cells evaluated in the presence of adriamycin and synergistic studies performed with several cell lines from the NCI tumor panel. The structures of the new compounds were determined using spectroscopic techniques. Single-crystal X-ray analysis was performed on the monoester, tropane-3 alpha,6 beta,7 beta-triol 3-phenylacetate (1).

Ethnomedicinally selected plants as sources of potential analgesic compounds: indication of in vitro biological activity in receptor binding assays.

A number of plant species used in traditional medicine for the relief of pain have been selected from the medicinal and scientific literature of China, South America, Asia and West Africa. Extracts were prepared and tested in three in vitro receptor radioligand binding assays to determine whether there was an indication of biological activity, in particular their selectivity to a single receptor implicated in the mediation of pain. The three neuropeptide receptors chosen were Bradykinin (BK II), expressed in Chinese hamster ovary cells (CHO), neurokinin 1 (NK 1) expressed in astrocytoma cells, and calcitonin gene related peptide (CGRP) which were all implicated in the mediation of acute pain in the mammaliancentral nervous system. The plant species chosen to investigate were Ageratum conyzoides, Barringtonia edulis, Croton tiglium, Ipomea pes-caprae, Panax ginseng, Physostigma venenosum, Sinomenium acutum, Solidago virgaurea, Symplocos leptophylla and Typhonium giganteum. The results showed that there was a strong indication of biological activity for some of the plants which are used ethnomedicinally to treat pain, in the three in vitro receptor binding assays used, and particular plant extracts exhibited selective action to a single receptor.

Evaluation of the purity of a purified, inactivated hepatitis A vaccine (VAQTA).

Manufacture of VAQTA, an inactivated hepatitis A virus vaccine, includes extensive purification of the intact virus particle to remove endogenous components from the host cell culture lysate as well as compounds introduced in the upstream purification process. Analysis of the final purified hepatitis A virus product by SDS-PAGE prior to inactivation shows that greater than 95% of the protein in the preparation is found in four protein bands, which have been confirmed to be hepatitis A virus capsid proteins VP0, VP1, VP2 and VP3 based on Western blot and mass spectrometry analyses. Validation of the manufacturing process and direct analysis of the final product were used to demonstrate that no other specific host cell-derived components are detected and that process residuals are all below the limits of detection of the assays used. Establishment of a rigorous standard of high purity for this product was pursued to minimize the impact of impurities during clinical development of this product and will facilitate the incorporation of this product into combination vaccines.

Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara.

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.

Seed Treatment with a Fungal or a Bacterial Antagonist for Reducing Corn Damping-off Caused by Species of Pythium and Fusarium.

Bioassays were conducted under greenhouse conditions to test the efficacy of antagonists applied to corn (Zea mays) seed for protection against seed rot and seedling damping-off at 18 and 25°C in a field soil artificially infested with a combination of Pythium ultimum, P. arrhenomanes, and Fusarium graminearum. Biomass of Gliocladium virens isolates Gl-3 or Gl-21, Trichoderma viride isolate Tv-1, or peat-based slurry of Burkholderia cepacia isolates Bc-B, Bc-T, or Bc-1 was coated individually onto corn seeds in one test, and Gl-3 or Bc-B at four inoculum levels was used in another test. Seed treatments with most of the biocontrol agents, as well as with the fungicide captan, significantly (P ≤ 0.05) increased seedling stand, plant height and fresh weight, and decreased root rot severity compared with untreated seeds in pathogen-infested soil. Coating seeds with the biocontrol fungus G. virens isolate Gl-3 was the most effective treatment, resulting in greater (P ≤ 0.05) seedling stand, plant height, and fresh weight, and lower (P ≤ 0.05) severity of root rot than those parameters from seeds treated with captan or other antagonists at both temperatures. The results from the seeds treated with Gl-3 were similar to those of untreated seeds in noninfested soil. In treatments with Bc-1, Bc-T, Bc-B, or Tv-1, incubation temperature affected plant emergence, root rot severity, plant height, and fresh weight (P ≤ 0.01). Conversely, in seeds coated with Gl-3 or Gl-21, these parameters were similar at both temperatures. The minimum number of propagules needed per corn seed to obtain plant emergence comparable to that from captan-treated seeds was between 104 and 105 CFU for Gl-3 and >108 for Bc-B. When propagules of Gl-3 were applied at a rate >106 CFU per seed, seedling emergence was greater (P ≤ 0.05) than that from captan-treated seeds.

Lupane derivatives from Lophopetalum wallichii with farnesyl protein transferase inhibitory activity.

Chloroform-soluble extracts of the stems and of the mixed stems and stem bark of Lophopetalum wallichii were found to be inhibitory in a farnesyl protein transferase (FPTase) bioassay system. During the course of activity-guided fractionation, the known lupane-type triterpenes, ochraceolide A (1), ochraceolide B (2), betulin, and lupeol and the new lupane lactone, dihydro ochraceolide A (4), were isolated. The stereochemistry of the epoxide group of ochraceolide B (2) was determined by preparation of both epoxide isomers [2, and the new semisynthetic derivative, 20-epi-ochraceolide B (3)] from 1. The structure of 4 was established by reduction of 1 with sodium borohydride. Compounds 1 and 2 exhibited significant inhibitory activity in the FPTase assay (IC50 values of 1.0 and 0.7 microgram/mL, respectively). Lupeol was found to be weakly active (IC50 65.0 micrograms/mL) in this test system, whereas no significant inhibition was detected for betulin or compounds 3 or 4. When evaluated against a panel of human cancer cells in culture, compounds 1 and 4 were modestly cytotoxic. Compounds 2 and 3 were not active in the panel.

Role of areca nut in the causation of oral submucous fibrosis: a case-control study in Pakistan.

A case-control study on chewing and smoking habits and oral submucous fibrosis (OSF) was undertaken in Karachi in 1989/90. Cases were patients detected with fibrous bands and leathery mucosa and hospital-based controls were matched by age and sex. Information on habits was collected by personal interview of 157 cases and 157 controls. Despite overall female preponderance, a substantial number of young men were enlisted. The male/female risks were found to be similar. Immigrants from India to Pakistan (Mohajir) had a similar risk status to local Punjabis. No differences between risks were found when comparing the three age categories, 21, 21-40, 41-60 yr. Among the cases, an increased risk was observed for areca nut chewing. This habit when practised alone appeared to have the highest risk (RR 154), followed by pan with or without tobacco (RR 64, 32 respectively). Logistic regression and discriminant analysis showed that daily consumption rates appeared to be more important with respect to risk than lifetime duration of habit. Tobacco habits were more prevalent amongst those 15 cases who presented with concurrent carcinoma and OSF: We conclude that areca nut chewing has a causal relationship with OSF: additional tobacco insult may be necessary for subsequent carcinoma development.

Epanolol as a model for assessing patient preference in anti-anginal drug therapy.

Since drug therapy of angina is likely to produce a similar degree of efficacy for most drugs in common use, treatment choice should additionally focus on other factors, notably adverse events, quality of life, and convenience. Improvements in these factors can also lead to better compliance and can aid the doctor by cutting down the number of patient visits required to optimize therapy. The authors have evaluated the patient's overall assessment of symptomatic relief and adverse experiences in a comparative manner by means of the two-period crossover design using the patient's declared treatment preference as the primary measurement. This encapsulates several factors in a single assessment that can be understood by both physician and patient. The authors carried out two such studies of epanolol (Visacor), a novel anti-anginal agent with both beta-1 selective antagonist activity and also beta-1 selective partial agonist activity. In one study (n = 608) the comparator was metoprolol, and in the other (n = 571) it was nifedipine. This article describes and evaluates the methodology of these studies. To assess preference optimally, each patient had to receive both treatments in short but clinically relevant treatment periods, with no washout. Re-entry into the second period, after withdrawal from the first, was permitted. Both studies showed advantages for epanolol, more marked in the case of nifedipine, arising from equivalent efficacy but fewer adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

Experiences with electrical stimulation devices for the control of chronic pain.

The results of a study involving the treatment of pain syndromes by electrical stimulation in 98 patients are reported. Advantages and disadvantages of three electrostimulation techniques--transcutaneous stimulation, peripheral nerve stimulation, and dorsal cord stimulation--are discussed. Also included is a brief discussion of the possible mechanism of suppression of pain stimuli.