Amantadine: neuromuscular blockade by suppression of ionic conductance of the acetylcholine receptor

Amantadine hydrochloride decreases the sensitivity of denervated mammalian muscle to iontophoretically applied acetylcholine. The drug depresses the amplitude of the end-plate current and reverses the slope of the relation between half-decay time and membrane potential suggesting that it alters the ionic conductance that is mediated by the acetylcholine receptor. Binding studies confirm that amantadine acts on the ion conductance modulator rather than the acetylcholine receptor.     

Induction of Apoptosis by Sinulariolide from Soft Coral through Mitochondrial-Related and p38MAPK Pathways on Human Bladder Carcinoma Cells

Sinulariolide, an isolated compound from the soft coral Sinularia flexibilis, possesses the anti-proliferative, anti-migratory and apoptosis-inducing activities against the TSGH bladder carcinoma cell. The anti-tumor effects of sinulariolide were determined by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell migration assay and flow cytometry, respectively. Sinulariolide inhibited the growth and migration of bladder carcinoma cells in a dose-dependent manner, as well as induced both early and late apoptosis as determined by the flow cytometer. Also, the sinulariolide-induced apoptosis is related to the mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome C, activation of caspase-3/-9, Bax and Bad, as well as suppression of Bcl-2/Bcl-xL/Mcl-1. Detection of the PARP-1 cleaved product suggested the partial involvement of caspase-independent pathways. Moreover, inhibition of p38MAPK activity leads to the rescue of the cell cytotoxicity of sinulariolide-treated TSGH cells, indicating that the p38MAPK pathway is also involved in the sinulariolide-induced cell apoptosis. Altogether, these results suggest that sinulariolide induces apoptosis against bladder cancer cells through mitochondrial-related and p38MAPK pathways.     

Multifunctionality of paddy fields in Taiwan

Paddy rice is the staple food in Taiwan, where rice farming always plays an important role in agricultural activities. The paddy fields and irrigation activities hold diversified functions, such as production, eco-environmental and living-associated functions. This paper is to provide information regarding the potential magnitude and monetary value of seven functions of paddy fields in Taiwan, including flood mitigation, fostering water resources, preventing soil erosion, purifying water, cooling air temperature, refreshing atmosphere and recreation. For quantification of the above values, replacement cost method (RCM), contingent valuation method (CVM), and the travel cost method (TCM) are adopted. In addition, the ratio of monetary value and their rice production commodity value (R) was also estimated. The results indicated that the flood mitigation function had a monetary value of US$ 389 million each year, and the ratio to the rice production value R was estimated at 37%. Water resource fostering function was US$ 501 million and R at 47%; soil erosion reduction function was US$ 433 million and R at 41%; water quality purification function was US$ 3 million and R at 0.3%; cooling air temperature function was US$ 961 million and R at 91%; refreshing air function was US$ 196 million and R at 19%, health and recreation function was US$ 987 million and R at 93%, respectively. Due to the significant importance of these externalities, it is recommended that the government should properly take into account the multifunctionalities in policy making to ensure sustainable development of agriculture.     

Effect of Oversulfation on the Composition,Structure, and In Vitro Anti-Lung Cancer Activity of Fucoidans Extracted from Sargassum aquifolium

Intensive efforts have been undertaken in the fields of prevention, diagnosis, and therapy of lung cancer. Fucoidans exhibit a wide range of biological activities, which are dependent on the degree of sulfation, sulfation pattern, glycosidic branches, and molecular weight of fucoidan. The determination of oversulfation of fucoidan and its effect on anti-lung cancer activity and related signaling cascades is challenging. In this investigation, we used a previously developed fucoidan (SCA), which served as a native fucoidan, to generate two oversulfated fucoidan derivatives (SCA-S1 and SCA-S2). SCA, SCA-S1, and SCA-S2 showed differences in compositions and had the characteristic structural features of fucoidan by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) analyses. The anticancer properties of SCA, SCA-S1, and SCA-S2 against human lung carcinoma A-549 cells were analyzed in terms of cytotoxicity, cell cycle, Bcl-2 expression, mitochondrial membrane potential (MMP), expression of caspase-3, cytochrome c release, Annexin V/propidium iodide (PI) staining, DNA fragmentation, and the underlying signaling cascades. Our findings indicate that the oversulfation of fucoidan promotes apoptosis of lung cancer cells and the mechanism may involve the Akt/mTOR/S6 pathway. Further in vivo research is needed to establish the precise mechanism whereby oversulfated fucoidan mitigates the progression of lung cancer.     

Evaluation of head-out constant volume body plethysmography for measurement of specific airway resistance in conscious, sedated sheep

OBJECTIVE: To evaluate the use of a modified whole body plethysmograph in awake sheep. ANIMALS: 10 healthy adult sheep. PROCEDURE: Concurrent measurements of specific airway resistance (sR(aw)) and pulmonary resistance (R(L)) were obtained using a novel noninvasive head-out constant-volume plethysmograph and esophageal balloon-pneumotachography, respectively. All data were collected before and after external resistive loading with 1 and 5.6 cm H2O/L/s. Functional residual capacity (FRC) was measured by helium dilution for computation of airway resistance (R(aw)) preloading (R(aw) = sR(aw)/FRC). RESULTS: The sR(aw) and R(L) were closely correlated in 10 adult sheep. Additionally, sR(aw), and R(L) accurately reflected the magnitude of added resistance. The mean FRC was 52 mL/kg and used to calculate R(aw). At baseline, the values for R(aw) were significantly correlated with sR(aw) and R(L). CONCLUSIONS AND CLINICAL RELEVANCE: Precise measurements of sR(aw) and R(aw) at baseline and sR(aw) after external resistive loading were obtained by use of this novel noninvasive plethysmographic technology. This method should have application to veterinary patients or animals used in research in which noninvasive rapid or serial measurements of sR(aw) in the conscious state are required.     

Detection of antibodies against Bordetella avium in turkeys by avidin-biotin enhancement of the enzyme-linked immunosorbent assay and the dot-immunobinding assay.

An avidin-biotin-enhanced enzyme-linked immunosorbent assay (AB-ELISA) and an avidin-biotin-enhanced dot-immunobinding (AB-DIB) assay for detecting antibody to Bordetella avium in turkey sera were developed and compared with the microagglutination (MA) test. Whole-cell antigen, biotin-labeled goat anti-turkey IgG conjugate, and horseradish-peroxidase-labeled streptavidin were used in the AB-ELISA and AB-DIB assay. The AB-ELISA and AB-DIB assay were sensitive, specific, and reproducible. These assays were superior to the MA test for measuring acquired and maternal antibodies against B. avium. All MA-positive sera were positive by two assays, but some sera negative by MA test had titers in the AB-ELISA and AB-DIB assay. AB-ELISA and AB-DIB titers showed a positive correlation (r = 0.866), and AB-ELISA was more sensitive than the AB-DIB assay.     

Self-trapping of dark incoherent light beams

"Dark beams" are nonuniform optical beams that contain either a one-dimensional (1D) dark stripe or a two-dimensional (2D) dark hole resulting from a phase singularity or an amplitude depression in their optical field. Thus far, self-trapped dark beams (dark solitons) have been observed using coherent light only. Here, self-trapped dark incoherent light beams (self-trapped dark incoherent wavepackets) were observed. Both dark stripes and dark holes nested in a broad partially spatially incoherent wavefront were self-trapped to form dark solitons in a host photorefractive medium. These self-trapped 1D and 2D dark beams induced refractive-index changes akin to planar and circular dielectric waveguides. The experiments introduce the possibility of controlling high-power coherent laser beams with low-power incoherent light sources such as light emitting diodes.     

A cytoplasmic protein inhibits the GTPase activity of H-Ras in a phospholipid-dependent manner

A cytoplasmic protein has been identified that inhibits the guanosine triphosphatase (GTPase) activity of bacterially synthesized, cellular H-Ras protein. This GTPase inhibiting protein is able to counteract the activity of GTPase activating protein (GAP), which has been postulated to function as a negative regulator of Ras activity. The potential biological importance of the GTPase inhibiting protein is further supported by its interaction with lipids. Phospholipids produced in cells as a consequence of mitogenic stimulation increase the activity of the GTPase inhibiting protein, as well as inhibit the activity of GAP. The interaction of such lipids with each of these two regulatory proteins would, therefore, tend to increase the biological activity of Ras and stimulate cell proliferation.     

Interferon induction in dogs.

A synthetic complex of poly (I)-poly (C) with poly-L-lysine and carboxymethyl cellulose (poly ICLC), as well as UV-inactivated Newcastle disease virus, B-1 strain, was used to induce interferon production in dogs. Several criteria were used for interferon specificity. The interferon response depended on dosage and route of inoculation. Serum interferon concentrations usually reached a peak by 8 hours after inoculation (AI), rapidly declined thereafter, and were nondetectable in most instances at 24 hours AI. Dogs responded less to interferon inducers when reinoculated 2 days after primary induction. The interferon response was biphasic (2 and 8 hours AI) when reinoculated 1 week after primary inoculation. Reinoculation 2 weeks after primary inoculation simulated the first response. Although both inducers caused severe lymphopenia in dogs, the toxic side effects would limit clinical use (in dogs) of poly ICLC, but not of UV-inactivated Newcastle disease virus.     

Mineral inclusions in diamond: temperature and pressure of equilibration

Two distinct suites of minerals included in natural diamond occur and probably represent different physical and chemical conditions during diamond growth. Minerals of the ultramafic suite appear to have equilibrated in the range 1000 degrees to 1300 degrees C between 45 and 65 kilobars, whereas the temperature range for minerals of the eclogitic suite is 850 degrees to 1250 degrees C. At present, models relating the partitioning of magnesium and iron between coexisting phases are not sufficiently rigorous to determine a value for the pressure of equilibration of these eclogitic suite inclusions.