Hydroxylation of benzphetamine and other drugs by a solubilized form of cytochrome P-450 from liver microsomes: Lipid requirement for drug demethylation

A solubilized hepatic microsomal enzyme system previously shown to catalyze the [omega]-hydroxylation of fatty acids also catalyzes the hydroxylation of drugs. Benzphetamine, aminopyrine, ethylmorphine, hexobarbital, norcodeine, and -nitroanisole undergo aerobic demethylation in the presence of NADPH and the resolved enzyme system. The required submicrosomal components for benzphetamine demethylation, as determined either by formaldehyde liberation or by NADPH oxidation, are cytochrome P-450, NADPH-cytochrome P-450 reductase, and a heat-stable lipid fraction. Similar requirements were shown for the oxidation of aminopyrine, ethylmorphine, and hexobarbital. Laurate and benzphetamine were found to be mutually inhibitory, as would be expected if a common "methyl hydroxylase" were involved. The solubilized cytochrome P-450 preparation exhibits a difference spectrum in the presence of benzphetamine with a peak at 392 m[mu] and a trough at 427 m[mu] and difference spectra with aniline and hexobarbital typical of those obtained with the microsomal bound form of this hemoprotein.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32916/1/0000296.pd

An empirical test of the theoretical population corrections to the Red Clump absolute magnitude

The mean absolute magnitude of the local red clump (RC) is a very well determined quantity due to the availability of accurate HIPPARCOS parallaxes for several hundred RC stars, potentially allowing it to be used as an accurate extra-galactic distance indicator. Theoretical models predict that the RC mean magnitude has non-linear dependencies on both age and metallicity. This suggests that a population correction, based on the star formation rate (SFR) and age-metallicity relation (AMR) of a particular system, should be applied to the local RC magnitude before it can be compared to the RC in that system in order to make a meaningful distance determination. Using a sample of 8 Galactic open clusters and the GC 47 Tuc, we determine the cluster distances, and hence the RC absolute magnitude in V, I and K, by applying our empirical main sequence fitting method, which utilizes a large sample of local field dwarfs with accurate HIPPARCOS parallaxes. The age and metallicity range of these 9 clusters enable us to make a quantitative assessment of the age and metallicity dependencies of the population corrections predicted by the theoretical models of Girardi & Salaris (2001). We find excellent agreement between the empirical data and the models in all 3 pass-bands, with no statistically significant trends or offsets, thus fully confirming the applicability of the models to single-age, single-metallicity stellar populations. Since, from the models, the population correction is a complicated function of both metallicity and age, if this method is used to derive distances to composite populations, it is essential to have an accurate assessment of the SFR and AMR of the system in question, if errors of several tenths of a magnitude are to be avoided.Comment: 9 pages, 5 figures. MNRAS accepte

Cytotoxic and antibacterial activities of endophytic fungi isolated from plants at the National Park, Pahang, Malaysia

<p>Abstract</p> <p>Background</p> <p>Endophytes, microorganisms which reside in plant tissues, have potential in producing novel metabolites for exploitation in medicine. Cytotoxic and antibacterial activities of a total of 300 endophytic fungi were investigated.</p> <p>Methods</p> <p>Endophytic fungi were isolated from various parts of 43 plants from the National Park Pahang, Malaysia. Extracts from solid state culture were tested for cytotoxicity against a number of cancer cell lines using the MTT assay. Antibacterial activity was determined using the disc diffusion method.</p> <p>Results</p> <p>A total of 300 endophytes were isolated from various parts of plants from the National Park, Pahang. 3.3% of extracts showed potent (IC₅₀< 0.01 μg/ml) cytotoxic activity against the murine leukemic P388 cell line and 1.7% against a human chronic myeloid leukemic cell line K562. <it>Sporothrix </it>sp. (KK29FL1) isolated from <it>Costus speciosus </it>showed strong cytotoxicity against colorectal carcinoma (HCT116) and human breast adenocarcinoma (MCF7) cell lines with IC₅₀values of 0.05 μg/ml and 0.02 μg/ml, respectively. Antibacterial activity was demonstrated for 8% of the extracts.</p> <p>Conclusion</p> <p>Results indicate the potential for production of bioactive agents from endophytes of the tropical rainforest flora.</p

A new visual -- near-infrared diagnostic to estimate the metallicity of cluster and field dwarf stars

We present a theoretical calibration of a new metallicity diagnostic based on the Stroemgren index m1 and on visual -- near-infrared (NIR) colors to estimate the global metal abundance of cluster and field dwarf stars. To perform the metallicity calibration we adopt alpha-enhanced evolutionary models transformed into the observational plane by using atmosphere models computed adopting the same chemical mixture. We apply the new visual - NIR Metallicity-Index-Color (MIC) relations to two different samples of field dwarfs and we find that the difference between photometric estimates and spectroscopic measurements is on average smaller than 0.1 dex, with a dispersion smaller than sigma = 0.3 dex. We apply the same MIC relations to a metal-poor (M 92) and a metal-rich (47 Tuc) globular cluster. We find a peak of -2.01+/-0.08 (sigma = 0.30 dex) and -0.47+/-0.01 (sigma = 0.42 dex), respectively.Comment: 11 pages, 6 figure, accepted for publication on A&

Vitamin D composition of Australian foods

Australia needs accurate vitamin D food composition data to support public health initiatives. Previously, limitations in analytical methodology have precluded development of a comprehensive database. We used liquid chromatography with triple quadrupole mass spectrometry (LC-QQQ) to analyse 149 composite samples representing 98 foods (primary samples n = 896) in duplicate for vitamin D3, 25-hydroxyvitamin D3 (25(OH)D3), vitamin D2, 25(OH)D2. The greatest concentrations of vitamin D3 were found in canned salmon and a malted chocolate drink powder (fortified); chicken eggs and chicken leg meat contained the most 25(OH)D3. Margarine (fortified) and chocolate contained the greatest concentrations of vitamin D2, with smaller amounts found in various meat products. 25(OH)D2 was detected in various foods, including meats, and was quantitated in lamb liver. These data advance knowledge of dietary vitamin D in Australia and highlight the importance of analysis of these four forms of vitamin D to accurately represent the vitamin D content of food

Time scales of Li evolution: a homogeneous analysis of open clusters from ZAMS to late-MS

We have performed a new and homogeneous analysis of all the Li data available in the literature for main sequence stars (spectral-types from late F to K) in open clusters. In the present paper we focus on a detailed investigation of MS Li depletion and its time scales for stars in the 6350-5500 K effective temperature range. For the first time, we were able to constrain the age at which non-standard mixing processes, driving MS Li depletion, appear. We have also shown that MS Li depletion is not a continuous process and cannot be simply described by a t^(-alpha) law. We confirm that depletion becomes ineffective beyond an age of 1-2 Gyr for the majority of the stars, leading to a Li plateau at old ages. We compared the empirical scenario of Li as a function of age with the predictions of three non-standard models. We found that models including only gravity waves as main mixing process are not able to fit the Li vs. age pattern and thus this kind of mixing can be excluded as the predominant mechanism responsible for Li depletion. On the other hand, models including slow mixing induced by rotation and angular momentum loss, and in particular those including also diffusive processes not related to rotation, can explain to some extent the empirical evidence. However, none of the currently proposed models can fit the plateau at old ages.Comment: 20 pages, 10 figures A&A accepte

International Validation of a Nomogram to Predict Recurrence after Resection of Grade 1 and 2 Nonfunctioning Pancreatic Neuroendocrine Tumors

Background: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. Methods: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. Results: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). Conclusions: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com

Native and exotic oysters in Brazil: comparative tolerance to hypercapnia

Environmental hypercapnia in shallow coastal marine ecosystems can be exacerbated by increasing levels of atmospheric CO2. In these ecosystems organisms are expected to become increasingly subjected to pCO2 levels several times higher than those inhabiting ocean waters (e.g.: 10,000 µatm), but still our current understanding on different species capacity to respond to such levels of hypercapnia is limited. Oysters are among the most important foundation species inhabiting these coastal ecosystems, although natural oyster banks are increasingly threatened worldwide. In the present study we studied the effects of hypercapnia on two important oyster species, the pacific oyster C. gigas and the mangrove oyster C. brasiliana, to bring new insights on different species response mechanisms towards three hypercapnic levels (ca. 1,000; 4,000; 10,000 µatm), by study of a set of biomarkers related to metabolic potential (electron transport system - ETS), antioxidant capacity (SOD, CAT, GSH), cellular damage (LPO) and energetic fitness (GLY), in two life stages (juvenile and adult) after 28 days of exposure. Results showed marked differences between each species tolerance capacity to hypercapnia, with contrasting metabolic readjustment strategies (ETS), different antioxidant response capacities (SOD, CAT, GSH), which generally allowed to prevent increased cellular damage (LPO) and energetic impairment (GLY) in both species. Juveniles were more responsive to hypercapnia stress in both congeners, and are likely to be most sensitive to extreme hypercapnia in the environment. Juvenile C. gigas presented more pronounced biochemical alterations at intermediate hypercapnia (4,000 µatm) than C. brasiliana. Adult C. gigas showed biochemical alterations mostly in response to high hypercapnia (10,000 µatm), while adult C. brasiliana were less responsive to this environmental stressor, despite presenting decreased metabolic potential. Our data bring new insights on the biochemical performance of two important oyster species, and suggest that the duration of extreme hypercapnia events in the ecosystem may pose increased challenges for these organisms as their tolerance capacity may be time limited.publishe

Fungal Endophyte Diversity in Sarracenia

Fungal endophytes were isolated from 4 species of the carnivorous pitcher plant genus Sarracenia: S. minor, S. oreophila, S. purpurea, and S. psittacina. Twelve taxa of fungi, 8 within the Ascomycota and 4 within the Basidiomycota, were identified based on PCR amplification and sequencing of the internal transcribed spacer sequences of nuclear ribosomal DNA (ITS rDNA) with taxonomic identity assigned using the NCBI nucleotide megablast search tool. Endophytes are known to produce a large number of metabolites, some of which may contribute to the protection and survival of the host. We speculate that endophyte-infected Sarracenia may benefit from their fungal associates by their influence on nutrient availability from within pitchers and, possibly, by directly influencing the biota within pitchers