Predicting intestinal and hepatic first-pass metabolism of orally administered testosterone 3 undecanoate 4

The bioavailability of orally administered drugs could be impacted by intestinal and 12 hepatic first-pass metabolism. Testosterone undecanoate (TU), an orally administered ester prodrug 13 of testosterone, is significantly subjected to first-pass metabolism. Yet, the individual contribution 14 of intestinal and hepatic first-pass metabolism is not well determined. Therefore, the aim of the 15 current study was to predict the contribution of each site. The hydrolysis-time profiles of TU 16 incubation in human liver microsomes and Caco-2 cell homogenate were used to predict hepatic 17 and intestinal first-pass metabolism, respectively. The in vitro half-life (t1/2 inv) for the hydrolysis of 18 TU in microsomal mixtures was 28.31 ± 3.51 min. By applying the "well-stirred" model, the fraction 19 of TU that could escape hepatic first-pass metabolism (FH) was predicted as 0.915 ± 0.009. The 20 incubation of TU in Caco-2 cell homogenate yielded t1/2 inv of 109.28 ± 21.42 min which was applied 21 in "Q gut" model to estimate the fraction of TU that would escape intestinal first-pass metabolism 22 (FG) as 0.114 ± 0.02. Accordingly, only 11% of the absorbed fraction of TU could escape intestinal 23 metabolism while 91% of which can pass hepatic metabolism. Hence, compared to the liver, the 24 intestinal wall is the main site where TU is significantly metabolised during first-pass effect. 2

The phytochemical content and antimicrobial activities of Malaysian Calophyllum canum (stem bark)

Recently there was huge increase in using of ‘herbal products’. These can be defined as plants, parts of plants or extracts from plants that are used for curing disease. However, Calophyllum species is a tropical plant and it has been used in traditional medicine, the limitation in safety and effectiveness information could lead to serious health problems. Providing information for communities by evaluating the phytochemical contents, antioxidant, antimicrobial and cytotoxic activities will improve the therapeutic values. Three main Calophyllum canum fractions (none – high polar) were tested to find out the phenolic, flavonoid, flavonol content, DPPH radical scavenging, reducing power and chelating iron ions. Also were tested against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Psedomonas aeruginosa, Candida albicans, and Cryptococcus neoformans. In addition, cytotoxic activity was assayed against lung cancer A549 cell line. The methanol fraction showed no bioactivity but achieved the highest amount of phenolic, flavonol and flavonoid contents, also it showed a significant result as antioxidant, reducing power and chelating agent. The n-hexane fraction achieved the minimum inhibitory concentration (MIC) value 12.5 μg. mL-1 against B. cereus while the MIC value for DCM fraction was 25 μg. mL-1. The DCM fraction was more active against S. aureus where the result was 50 μg. mL-1 while the n-hexane fraction was 100 μg. mL-1. The three main fractions have shown no activity against gram negative bacterial and fungal. The n-hexane and DCM fractions have shown cytotoxicity against lung cancer cell line; the 50 % inhibition concentration (IC50) was 22 ± 2.64 and 32 ± 3.78 μg. mL-1 respectively. The results were statistically significant (P < 0.05). Among the results, C. canum fractions proved to be effective against gram positive bacterial and anti-proliferation activity. Also it showed antioxidant activity as well. The results provided beneficial information for communities as well as can help to search for alternative drugs, and will contribute to establish safe and effective use of phytomedicines in the treatment of diseases

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Phytochemical and biological activity study of Calophyllum canum

Calophyllum canum or (Bintangor Batu) is a Malaysian plant which belongs to the family of Guttiferae. This family considered being a source of xanthons and flavonoids, which has shown lately the biological activity against bacterial, fungus and cancer cells. The most well known species Calophyllum Ianigerum which found in Sarawak shown a biological activity against human immunodeficiency virus (HIV). During the last three decades, the studies have been done for isolating these certain compounds. In this research we are concentrating on phytochemical study of C.canum. The stem bark of this plant dried and grinded to get a powder form, and then it has been extracted by using Soxhlet extraction method, where the extraction started with Hexane, Ethyl acetate and Methanol. The extracts were isolated by using Chromatography method (vacuum and column), the hexane and ethyl acetate fraction yield six pure compounds marker as (cc1-cc6). The crude extract examined against bacterial gram (positive and negative), by using the disk diffusion method. Also it has been tested to observe any antioxidant behaviors. As well as the crude and identified compounds will be tested for there anticancer activity against lung, leukemia, colon, breast and cervix cancer. The cell growth will be monitored by inhibition of cell proliferation with MTT assay. For the identification, we used the spectroscopic techniques (NMR, IR, MS, and UV/Vis) for interpretation the structure of these pure compounds. The results are under processing to draw the structure

Isolation and cytotoxic activity study of phytochemicals from Calophyllum canum

Calophyllum canum is a large tree which grows in South East Asia and which is popular for its timber. This plant belongs to the family Guttiferae; a family that boasts species which are rich in bioactive phytochemicals. The present study was conducted to screen for the antiproliferation activity of three crude extracts from the stem bark of C. canum. The activity of an isolated compound against canacer cells was also reported. The three extracts; n-hexane, ethyl acetate and methanol extracts, were screened on human cervical (C33A), colon (CACO2), lung (A549), esophageal (TE1), breast (MCF7) cancer cell lines along with normal human dermal fibroblast cells (NHDF) and leukemia cancer cells (K562) . The MTT assay and direct counting by tryphan blue were used to assess the antiproliferation activity of the extracts on the cell lines. The study revealed that the n-hexane extract had the strongest antiproliferation activity, followed by the methanol extract. n-hexane strongly inhibited the growth of TE1 and MCF7 cell lines. IC50 for n-hexane and methanol extract activity on the A549 cell line was found to be 27.96 µg/mL and 78.9 µg/mL respectively. The IC50 for the n-hexane extract activity on the NHDF cell line was found to be 70.59 µg/mL. The ethyl acetate extract showed no activity against any of the cell lines. An isolated compound labeled as CE2 was found to be active against K562 cells with IC50 value of 11µg/mL

Antioxidant and cytotoxic activities of Calophyllum rubiginosum

Clusiaceae / Guttiferae an evergreen shrubs or trees, it is considered as a family of 27 genera and 1090 species. Calophyllum rubiginosum one of these species and belongs to this family. In Malaysia they use it as folk remedies, where they believe its’ activity. Problem: Evaluation of antioxidant and cytotoxic activities of three fractions. n-hexane, dichloromethane (DCM) and methanol (MeOH) of Calophyllum rubiginosum species. Approach: The three main fractions were tested to find out the antioxidant capacity using three different methods, DPPH radical scavenging, reducing power and chelating iron ions. The fractions were tested against lung cancer A-549 cell line to assess the anti-proliferation activity. Results: The MeOH fraction showed no effect against lung cancer cell line but achieved a significant result in antioxidant testing. The DCM and n-hexane fractions considered as moderate antioxidant agent, they showed a significant result against lung cancer cell line. Non and semi polar fractions were able to inhibit the proliferation of A-549 cell line at low concentration. The results were statistically significant (P< 0.05). Conclusions: C. rubiginosum fractions have showed significant activity. DCM and n-hexane fractions proved to be effective against A-549 lung cancer cell line, where they were able to disturb the cell proliferation. These results can benefit the local community, and to guide how to use this plant

A Comprehensive Study of Malware Detection in Android Operating Systems

Android is now the world's (or one of the world’s) most popular operating system. More and more malware assaults are taking place in Android applications. Many security detection techniques based on Android Apps are now available. The open environmental feature of the Android environment has given Android an extensive appeal in recent years. The growing number of mobile devices are incorporated in many aspects of our everyday lives. This&nbsp; paper gives a detailed comparison that summarizes and analyses various detection techniques. This work examines the current status of Android malware detection methods, with an emphasis on Machine Learning-based classifiers for detecting malicious software on Android devices. Android has a huge number of apps that may be downloaded and used for free. Consequently, Android phones are more susceptible to malware. As a result, additional research has been done in order to develop effective malware detection methods. To begin, several of the currently available Android malware detection approaches are carefully examined and classified based on their detection methodologies. This study examines a wide range of machine-learning-based methods to detecting Android malware covering both types dynamic and static

Apoptosis, antimicrobial and antioxidant activities of phytochemicals from Garcinia malaccensis Hk.f

Objective: The paper reported chemical constituents of stembark of Garcinia malaccensis together with apoptotic, antimicrobial and antioxidant activities. Methods: Purification and structure elucidation were carried out by chromatographic and spectroscopic techniques, respectively. MTT and trypan blue exclusion methods were performed to study the cytotoxic activity. Antibacterial activity was conducted by disc diffusion and microdilution methods, whereas antioxidant activities were done by ferric thiocyanate method and DPPH radical scavenging. Results: The phytochemical study led to the isolation of -mangostin and cycloart-24-en-3-ol. -Mangostin exhibited cytotoxic activity against HSC-3 cells with an IC50 of 0.33 M. β- and α-mangostin showed activity against K562 cells with IC50 of 0.40 M and 0.48 M, respectively. -Mangostin was active against Gram-positive bacteria, Staphylococcus aureus and Bacilus anthracis with inhibition zone and MIC value of (19 mm; 0.025 mg/mL) and (20 mm; 0.013 mg/mL), respectively. In antioxidant assay, -mangostin exhibited activity as an inhibitor of lipid peroxidation. Conclusion: G. malaccensis presence - and -mangostin and cycloart-24-en-3-ol. -Mangostin was found very active against HSC-3 cells and K562. The results suggest that mangostins derivatives have the potential to inhibit the growth of cancer cells by inducing apoptosis. In addition, -and -mangostin was found inhibit the growth of Gram-positive pathogenic bacteria and also showed the activity as an inhibitor of lipid peroxidation

Chemical constituents and bioactivities of Garcinia malaccensis Hk.f

Garcinia malaccensis Hk.f (Guttiferae) is closely resembled to G. mangostana and G. hombroniana. The genus of Garcinia, especially Garcinia mangostana is well known as a medicinal plant in South-east Asia and is used in traditional medicine. The paper reported the chemical constituents of the stembark of Garcinia malaccensis together with cytotoxic, antimicrobial and antioxidant activities. Purification and structure elucidation were carried out by chromatographic and spectroscopic techniques, respectively. MTT and trypan blue exclusion methods were performed to study the cytotoxic activity. Antibacterial activity was conducted by disc diffusion and microdilution methods, whereas antioxidant activities were done by ferric thiocyanate method and DPPH radical scavenging. The phytochemical study led to the isolation of -mangostin and cycloart-24-en-3-ol. -Mangostin exhibited cytotoxic activity against HSC-3 cells with an IC50 of 0.33 M. β- and α-mangostin showed activity against K562 cells with IC50 of 0.40 M and 0.48 M, respectively. -Mangostin was active against Gram-positive bacteria, Staphylococcus aureus and Bacilus anthracis with inhibition zone and MIC value of (19 mm; 0.025 mg/mL) and (20 mm; 0.013 mg/mL), respectively. In antioxidant assay, -mangostin exhibited activity as an inhibitor of lipid peroxidation. G. malaccensis presence - and -mangostin and cycloart-24-en-3-ol. -Mangostin was found very active against HSC-3 cells and K562. The results suggest that mangostins derivatives have the potential to inhibit the growth of cancer cells by inducing apoptosis. In addition, -and -mangostin was found inhibit the growth of Gram-positive pathogenic bacteria and also showed the activity as an inhibitor of lipid peroxidation. Keywords: Garcinia malaccensis, Guttiferae, apoptosis, antibacterial, antioxidan