Pyrazinamide and Pyrazinoic Acid Activity against Tubercle Bacilli in Cultured Human Macrophages and in the BACTEC System

Pyrazinamide (PZA) has becomean essential component of current 6-month regimens for therapy of tuberculosis. Susceptible strains of tubercle bacilliconvert PZA to pyrazinoic acid (POA)through pyrazinamidase (PZase), which resistant strains and Mycobacterium bovis bacilleCalmette-Guerin lack. PZA susceptibility results obtained in cultured human macrophages were compared with those in the broth BACTEC system with 7H12 medium at pH 6.0 for strains known to bePZasepositive or -negative. Although added PDA was unable to inhibit tubercle bacilli in cultured macrophages, it was able to inhibit them at very high concentrations in the BACTEC broth. Intracellularly formed PDA would not be able to escape from the macrophage, and therefore would accumulate sufficiently to lower pH to toxic levels for tubercle bacilli. The results suggest that the cultured macrophages contribute actively or passively to the effectiveness of PZA, such as through the proposed mechanism of low pH generated by PZase in the phagolysosome

The use of anthracene as a model compound in a comparative study of hydrous pyrolysis methods for industrial waste remediation

Polycyclic aromatic hydrocarbons are very stable compounds and tend to bioaccumulate in the environment due to their high degree of conjugation and aromaticity. Hydrous pyrolysis is explored as a technique for the treatment of industrial water containing PAH, using anthracene as a model compound. The reactivity of anthracene under a range of temperatures and durations are studied in this paper. Aliquots of 1.0-10.0mg of anthracene in a range of 1.0-5.0 mL of H(2)O are subjected to hydrous pyrolysis under varied conditions of temperature, reagents and duration. The conditions include oxidising systems comprising distilled water, hydrogen peroxide and Nafion-SiO(2) solid catalyst in water; and reducing systems of formic acid and formic acid/Nafion-SiO(2)/Pd-C catalysts to assess a range of redox reaction conditions. Oxygen in air played a role in some of the reaction conditions. Pyrolysed products were identified and quantified by the use of Gas Chromatography-Mass Spectrometry (GC-MS). The major products were anthrone, anthraquinone, xanthone from oxidation; and multiple hydro-anthracene derivatives from reductive hydogenation. The nature of reaction conditions influenced the extent of anthracene degradation. The products formed are more reactive (less stable) as compared to anthracene the starting material and will therefore be less persistent in the environment

Physical activity and academic achievement among Norwegian adolescents: Findings from a longitudinal study

Regular physical activity (PA) has been associated with academic achievement, but the evidence is mainly based on cross-sectional research and self-reported measures of PA. The purpose of the current study was to explore the longitudinal relationship between objectively measured PA and academic achievement among a cohort of adolescents in Norway between 2016 and 2018. As a secondary aim, an indirect relationship via waist circumference (WC) and sleep duration was assessed. Data from 599 adolescents (54.4% female, mean age at baseline ± SD 13.3 ± 0.3 years) were collected annually during their three years at lower secondary school. PA was measured objectively using accelerometry. Academic achievement was assessed using grade point average (GPA) from school records. Linear regression analysis was performed to explore associations between longitudinal changes in measures of PA (Total PA and moderate-to-vigorous PA [MVPA]) and academic achievement directly or via mediators. Results showed no significant associations between Total PA or MVPA and academic achievement, either in the main analyses or through mediation of WC and sleep duration. The results contribute to a growing evidence base of studies showing no association between objectively measured PA and academic achievement among adolescents.publishedVersio

Preliminary photochemical studies of fluorene in various aqueous media

-The current study investigates the direct photochemical degradation of aqueous fluorene with the aid of a 125W polychromatic medium, pressure Hg lamp. The purpose was to test the effectiveness of the lamp in irradiation using fluorene spiked solution as substrate. A 700 ml volume of fluorene solution of 0.002 mg/l was irradiated batch-wise at 1, 3, 6, 12, 18, 24 and 48 h. The amount of fluorene removal was studied for fluorene solutions prepared from , neutral (distilled water), acidic (by adjusting pH with hydrochloric acid, HCl), basic (by adjusting pH with sodium hydroxide, NaOH) and saline (addition of sodium chloride, NaCl) solutions and there was 95.95, 92.35, 96.65 and 97.15 % removal respectively after 48 h of irradiation. The major degradation product identified was fluorenone. The different media did not significantly affect the rate of fluorene degradation

The longitudinal association between objectively measured physical activity and mental health among Norwegian adolescents

Background: Mental health among young people in many countries, including Norway, seems to be deteriorating. Physical activity (PA) has been positively associated with mental health. However, methodological issues related to study design and measurement of PA and mental health outcomes currently limits our understanding of the relationship. The purpose of the present study is to explore the prospective relationship between objectively measured PA and mental health outcomes. More specifically, volume (total PA), intensity (moderate-to-vigorous PA [MVPA]) and sedentary behaviour (SED) were explored in relation to mental health problems (MHP) and mental wellbeing (MWB). Methods: Data from 599 adolescents (54.4% female, mean age at baseline ±SD 13.3 ± 0.3 years) were collected annually during their 3 years (T1, T2 and T3) at lower secondary school. PA was measured using accelerometry. MWB was measured using the ‘Warwick-Edinburgh Mental Wellbeing Scale’ and MHP by the ‘Strengths and Difficulties Questionnaire’. Multiple linear regression was performed to explore relationships between changes in PA/SED (between T1-T3) and MWB/MHP (at T3). The term ‘movement categories’ was used to refer to components on the movement continuum and includes volume (total PA), intensity (MVPA) and SED. Results: Among boys, any increase in SED was positively associated with MWB (β = 0.05, 95% CI: 0.01 to 0.10), whereas a small positive association between an increase in total PA (volume) and MWB was found among girls (β = 1.13, 95% CI: 0.05 to 2.21). There were no associations between changes in any movement categories [total PA (volume), MVPA, SED] and score on MHP at T3, neither for girls nor boys. Conclusion: This study provided no clear evidence of any association between change in volume or intensity of PA and MHP among an overall healthy adolescent study sample. There was, however, evidence of a relationship between increased SED and MWB among boys and increased volume of PA and MWB among girls. The relationship between movement categories and mental health may depend on the measurement used to assess both PA/SED and variables of mental health. Future research would be strengthened by researchers clarifying what construct of mental health is being used and measured.publishedVersio

A New CYP2E1 Inhibitor, 12-Imidazolyl-1-dodecanol, Represents a Potential Treatment for Hepatocellular Carcinoma

Cytochrome P450 2E1 (CYP2E1) is a key target protein in the development of alcoholic and nonalcoholic fatty liver disease (FLD). The pathophysiological correlate is the massive production of reactive oxygen species. The role of CYP2E1 in the development of hepatocellular carcinoma (HCC), the final complication of FLD, remains controversial. Specifically, CYP2E1 has not yet been defined as a molecular target for HCC therapy. In addition, a CYP2E1-specific drug has not been developed. We have already shown that our newly developed CYP2E1 inhibitor 12-imidazolyl-1-dodecanol (I-ol) was therapeutically effective against alcoholic and nonalcoholic steatohepatitis. In this study, we investigated the effect of I-ol on HCC tumorigenesis and whether I-ol could serve as a possible treatment option for terminal-stage FLD. I-ol exerted a very highly significant antitumour effect against hepatocellular HepG2 cells. Cell viability was reduced in a dose-dependent manner, with only the highest doses causing a cytotoxic effect associated with caspase 3/7 activation. Comparable results were obtained for the model colorectal adenocarcinoma cell line, DLD-1, whose tumorigenesis is also associated with CYP2E1. Transcriptome analyses showed a clear effect of I-ol on apoptosis and cell-cycle regulation, with the increased expression of p27Kip1 being particularly noticeable. These observations were confirmed at the protein level for HepG2 and DLD-1 cells grafted on a chorioallantoic membrane. Cell-cycle analysis showed a complete loss of proliferating cells with a simultaneous increase in S-phase arrest beginning at a threshold dose of 30 μM. I-ol also reduced xenograft tumour growth in nude mice. This antitumour effect was not associated with tumour cachexia. I-ol was not toxic to healthy tissues or organs. This study demonstrates for the first time the therapeutic effect of the specific CYP2E1 inhibitor I-ol on the tumorigenesis of HCC. Our findings imply that I-ol can potentially be applied therapeutically on patients at the final stage of FLD. © 2021 Torsten Diesinger et al

Integrative medicine during the intensive phase of chemotherapy in pediatric oncology in Germany: a randomized controlled trial with 5-year follow up

Background: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients. Methods: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales. Results: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up. Discussion: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown