N-methylated beta-carbolines protect PC12 cells from cytotoxic effect of MPP+ by attenuation of mitochondrial membrane permeability change

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of beta-carbolines (harmaline and harmalol) on the MPP(+)-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. beta-Carbolines and antioxidants (superoxide dismutase, catalase, ascorbate or rutin) prevented the loss of cell viability in PC12 cells treated with 250 microM MPP(+), while the effects of N-acetylcysteine and dithiothreitol were not observed. beta-Carbolines reduced the condensation and fragmentation of nuclei caused by MPP(+) in PC12 cells. beta-Carbolines alone did not exhibit a significant cytotoxic effect on PC12 cells. beta-Carbolines (50 microM) inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, activation of caspase-3, formation of reactive oxygen species (ROS) and depletion of GSH caused by MPP(+) in PC12 cells. beta-Carbolines reduced the hydrogen peroxide- or SIN-1-induced cell death in PC12 cells. The results suggest that beta-carbolines may attenuate the MPP(+)-induced viability loss in PC12 cells by inhibition of change in the mitochondrial membrane permeability and by antioxidant effect.     

The alterations of N-Methyl-D-aspartate receptor expressions and oxidative DNA damage in the CA1 area at the early time after ischemia-reperfusion insult

Delayed neuronal death in the CA1 of the hippocampus following global ischemia has been evoked by both the activation of N-methyl-D-aspartate receptor (NR) and the generate reactive oxygen species in the neurons. In the present study, we investigated whether oxidative DNA damages may be correlated with NR subunits (NR1 and NR2A/B) expression following ischemia insults in vivo. Thirty minutes after ischemia-reperfusion, the intensities of both NR and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunoreactivities were markedly increased in neurons of CA1. However, NR2A/B and 8-OHdG immunoreactivities were enhanced in CA1 over 24 h after ischemia although NR1 immunoreactivity was decreased. These results suggest that oxidative stress and excitotoxicity in the CA1 may simultaneously trigger neuronal damages at early time after ischemia, and free radical damage including oxidative DNA damage may eventually promote the delayed neuronal death in this region.     

RNA synthesis and aminoacyl transfer RNA activity of L-2071 cells exposed to dieldrin and DDT

In L-2071 tissue culture cells, 50 ppm (50 g/ml culture medium) each of dieldrin or DDT reduced total cell count and the rate of¹⁴C-leucine incorporation into protein and¹⁴C-uridine incorporation into total RNAs; this was the result of an increased rate of¹⁴C-uridine incorporation into cytoplasmic soluble and 4S RNA cellular fraction. Total amino acid acceptor activity decreased with dieldrin and DDT treatments, which suggests an actual decrease in functional tRNAs. Dieldrin reduced glutamyl- and aspartyl-tRNA activities whereas phenylalanyl-, tyrosyl-, threonyl-, leucyl-, isoleucyl-, seryl-, and prolyl-tRNA activities decreased with both pesticides. Valyl-, lysyl-, glycyl-, alanyl-, histidyl-, and arginyl-tRNA activities were only slightly changed. The effect of dieldrin was generally greater than that of DDT. In addition, there was degradation of 28S and 18S RNAs to fragments isolated with 4S RNAs. Cells treated with 0.5 and 10 ppm levels of dieldrin demonstrated decreased¹⁴C-uridine incorporation into 28S RNAs and increased incorporation into 18S and 4S RNAs after 3 hours and 3 to 6 hours, respectively. Incorporation levels returned to near control levels, thereafter, in whole cell preparations, but remained different from controls when nuclear and cytoplasmic fractions were assessed individually.     

Concentration andpH dependent steady-state volume of distribution of methotrexate estimated by a simple physiologically based method

The effects of plasma concentration and pH on the steady-state volume of distribution, V_ss,of methotrexate (MTX) were studied in five conditioned male beagle-mongrel dogs. Steady-state plasma MTX concentrations of approximately 1, 20, and 100g/ml were targeted for by i.v. bolus doses followed by i.v. infusions. An isotonic solution of sodium bicarbonate or ammonium chloride was simultaneously infused for the purpose of inducing plasma pH change, while the infusion of an isotonic solution of sodium chloride served as a control. Plasma and urine concentrations of MTX were quantitated by a sensitive high-performance liquid chromatographic method, and the V_ss of MTX was estimated by a recently reported physiologically based method of Chiou and Lam. Statistically significant (p<0.05) concentration and plasma pHdependent V_ss of MTX were observed. Concentration dependence of V_ss was noted in sodium chloride and ammonium chloride infused dogs, but not in bicarbonate treated dogs. There was an average 50.0 and 44.8% increase in V_ss at 1 g/ ml relative to the two higher concentrations (20 and 100 g/ ml) for dogs treated with ammonium and sodium chloride, respectively. However, V_ss of MTX at the targeted concentrations of 20 and 100 g/ml was relatively constant. Plasma pHdependence of V_ss was observed only at the plasma concentration of 1 g/ml, and on the average, ammonium chloride and sodium chloride treatments resulted in 50.0 and 31.3% higher V_ss,respectively, when compared with the bicarbonate treatment. These phenomena appear to be adequately explained by the reported tissue uptake kinetics of MTX.This research was supported in part by a grant from the National Cancer Institute, CA-29754.Abstracted from a dissertation submitted in 1984 by Chung Y. Lui to the Graduate College, University of Illinois at Chicago, in partial fulfillment of Doctor of Philosophy Degree requirements.     

How different health literacy dimensions influences health and well‐being among men and women: The mediating role of health behaviours

BackgroundHealth literacy, the ability to access, understand, evaluate and apply health information, was found to contribute to positive health outcomes, possibly via promoting healthy behaviours. However, the specific pathways linking different health literacy skills to health and well‐being have remained unclear.MethodsA cross‐sectional survey with structural questionnaires was administered among 2236 adults in Hong Kong (mean age = 46.10 ± 19.05). Health literacy was measured by HLS‐Asian‐47. Participants'' physical conditions and subjective well‐being were predicted by health literacy and health behaviours with structural modelling path analysis.ResultsHealth literacy in finding and understanding information showed a direct effect on enhancing physical health, while applying information capacity had an indirect positive effect via promoting health behaviours, which was moderated by sex. Only among women, this indirect effect predicting fewer physical symptoms and better well‐being was significant.ConclusionsDifferent health literacy dimensions showed distinct direct and indirect pathways in influencing health for men and women. Based on the findings, skill trainings should be developed to enhance both gender''s abilities of finding and understanding health information, while the ability of applying health information should also be improved for modifying lifestyle and promoting health, particularly for women.Patient or Public ContributionTwo thousand and two hundred thirty‐six adults from different districts of Hong Kong participated in the study, and responded to questions on health literacy, behaviours and health status.     

Clinical Characteristics and Risk Factors of Early-Onset Tuberculosis After Liver Transplantation

BackgroundWe encountered some cases of early-onset tuberculosis (TB) after liver transplant (LT), leading to further transmission to other immunocompromised patients. Therefore, we investigated the clinical characteristics and risk factors of early-onset TB after LT.MethodsAll adult patients with TB after LT from 1996 to 2019 were retrospectively enrolled. Our hospital did not screen for latent TB infection (LTBI) in LT recipients because of concerns regarding the potential hepatotoxicity of anti-TB medication. Patients were categorized into 2 groups based on the TB onset time after LT: early-onset TB (≤2 months) and late-onset TB (>2 months).ResultsOf 4301 LT recipients, 91 patients developed TB after LT (2.1%). The median time from LT to TB development was 9.4 months. Of these 91 patients, 11 were classified as having early-onset TB (12.1%). Patients with early-onset TB had a greater pretransplant TB history than patients with late-onset TB (36.4% vs 11.3%, P = .048).ConclusionThis unusual early-onset TB was more common in patients with a pretransplant TB history, suggesting the possibility of missed TB or full manifestation of the indolent course of TB after LT. Therefore, LT recipients with a pretransplant TB history should undergo thorough screening for active TB and consider prophylaxis.     

Dark Tea: A popular beverage with possible medicinal application

Tea is a famous beverage that is produced from leaves of Camellia sinensis. Amongst the six major tea categories in China, dark tea is the only one that involves microbial fermentation in the manufacturing process, which contributes unique flavors and functions for the tea. In the recent decade, the reports about the biofunctions of dark teas have increased rapidly. Therefore it may be the proper time to consider dark tea as one potential homology of medicine and food. In this viewpoint, our current understanding of the chemical constituents, biological activities and possible health beneficial effects of dark teas were introduced. Some future directions and challenges to the development perspectives of dark teas were also discussed.