Toxicokinetics and molecular interaction of [14C]-formaldehyde in rats

The excretion, tissue distribution, and binding of [¹⁴C]-formaldehyde were studied at different time intervals in male rats following a single intraperitoneal injection of 72 mg CH₂O (14.7 Ci)/ kg body weight. Within 30 min, 10% of the total dose was recovered in expired air as¹⁴CO₂ and by the end of 72 hr, 41% of the administered dose was eliminated through expired air. The total elimination of¹⁴CH₂O activity in urine and feces in 72 hr was 15%. Erythrocytes retained significant amounts of radioactivity, even at the end of 72 hr. Substantial levels of radioactivity were detected in most tissues one hr after administration, indicating a fast absorption and rapid distribution. Subcellular fractionation of the tissues showed that the highest levels of relative percent binding was in the microsomal fraction, whereas cytosol fractions contained lowest levels of bound radioactivity. DNA, RNA, protein and lipid fractions of liver and spleen tissues showed significantly elevated levels of¹⁴C-incorporation as compared to other tissues. Thein vivo incorporation of¹⁴C-activity showed an increased association of¹⁴CH₂O with RNA in all the tissues. The maximum registration of radioactivity in RNA was at 48 hr after administration. Significantly higher amounts of¹⁴C-activity were registered in DNA of all tissues. The maximum registration of radiolabel in DNA of most tissues was at 12 hr after the¹⁴CH₂O administration. The liver DNA showed maximal levels at 3 hr with a second peak at 48 hr.Substantial amounts of bound radioactivity in nucleic acids of all the tissues were observed even 72 hr after dosing. The relationship between macromolecular association and formaldehyde toxicity has been discussed.     

Abortion law reform in Nepal

Across four decades of political and social action, Nepal changed from a country strongly enforcing oppressive abortion restrictions, causing many poor women’s long imprisonment and high rates of abortion-related maternal mortality, into a modern democracy with a liberal abortion law. The medical and public health communities supported women’s rights activists in invoking legal principles of equality and non-discrimination as a basis for change. Legislative reform of the criminal ban in 2002 and the adoption of an Interim Constitution recognizing women’s reproductive rights as fundamental rights in 2007 inspired the Supreme Court in 2009 to rule that denial of women’s access to abortion services because of poverty violated their constitutional rights. The government must now provide services under criteria for access without charge, and services must be decentralized to promote equitable access. A strong legal foundation now exists for progress in social justice to broaden abortion access and reduce abortion stigma.     

Regeneration of a deactivated surface functionalised polyacrylonitrile supported Fenton catalyst for use in wastewater treatment

Successful attempts to regenerate a used surface functionalised nanocoated polyacrylonitrile (PAN) catalyst are described here. During use in wastewater treatment, the novel Fenton catalyst (F1) is deactivated due to iron loss caused by acid hydrolysis. In this study the deactivated catalyst (D1) is subjected to reactions with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), followed by reactions with either hydroxylamine to give sample T1 or hydroxylamine and hydrazine to give sample T2. The samples were then impregnated with iron(iii) salt to give either Fe-T1 or Fe-T2. The catalysts were characterized by Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR), Atomic Absorption (AA) and UV/VIS spectroscopies, Scanning Electron Microscopy (SEM) with energy-dispersive X-ray (EDX) spectroscopy and Electron Spin Resonance (ESR) spectroscopy. The iron on the regenerated catalyst was found to be in complexed form but had deposited iron oxide species as well. The catalysts were tested in batch mode and compared with the fresh modified PAN catalyst in the degradation of the dye Reactive Orange 16 (RO-16) with analysis by UV/VIS spectroscopy. The reactivated catalysts prepared with EDC were found to be more active and faster (as measured at 120 min) in decolourising RO-16 than the fresh catalytic mesh but also with a higher degree of Fe leaching (0.85% loss of iron per gram of Fe-T2 catalyst over 6 cycles compared to 0.32% loss of Fe per gram of F1 catalyst over 6 cycles). This leaching was found not to contribute significantly to degradation of the dye and the preliminary results suggest that the regime can be used for catalyst regeneration encouraging industrial uptake.

Successful attempts to regenerate a used surface functionalised nanocoated polyacrylonitrile (PAN) catalyst are described here.     

Accumulation of Cadmium in Transplanted Lichen Pyxine cocoes (Sw.) Nyl., with Reference to Physiochemical Variation and Kinetics of Cadmium Biosorption

Bulletin of Environmental Contamination and Toxicology - The safe utilization and risk assessment of produced water (PW) from oil and gas fields for desert irrigation have received increasing...     

Prevalence of chronic hepatitis B virus infection before and after implementation of a hepatitis B vaccination program among children in Nepal

Background

In Nepal, an estimated 2–4% of the population has chronic hepatitis B virus (HBV) infection. To combat this problem, from 2002 to 2004, a national three dose hepatitis B vaccination program was implemented to decrease infection rates among children. The program does not currently include a birth dose to prevent perinatal HBV transmission. In 2012, to assess the impact of the program, we conducted a serosurvey among children born before and after vaccine introduction.

Methods

In 2012, a cross-sectional nationally representative stratified cluster survey was conducted to estimate hepatitis B surface antigen (HBsAg) prevalence among children born from 2006 to 2007 (post-vaccine cohort) and among children born from 2000 to 2002 (pre-vaccine cohort). Demographic data, as well as written and oral vaccination history were collected. All children were tested for HBsAg; mothers of HBsAg positive children were also tested. Furthermore, we evaluated the field sensitivity and specificity of the SD Bioline HBsAg rapid diagnostic test by comparing results with an enzyme immunoassay.

Results

Among 2181 post-vaccination cohort children with vaccination data by either card or recall, 86% (95% confidence interval [CI] 77–95%) received ≥3 hepatitis B vaccine doses. Of 1200 children born in the pre-vaccination cohort, 0.28% (95% CI 0.09–0.85%) were positive for HBsAg; of 2187 children born in the post-vaccination cohort, 0.13% (95% CI 0.04–0.39%) were positive for HBsAg (p = 0.39). Of the six children who tested positive for HBsAg, two had mothers who were positive for HBsAg. Finally, we found the SD Bioline HBsAg rapid diagnostic test to have a sensitivity of 100% and a specificity of 100%.

Conclusions

This is the first nationally representative hepatitis B serosurvey conducted in Nepal. Overall, a low burden of chronic HBV infection was found in children born in both the pre and post-vaccination cohorts. Current vaccination strategies should be continued.     

Effect of dietary administration of Lathyrus sativus pulse on intestinal biochemical parameters in normal and scorbutic guinea pigs

Objective In order to investigate that ascorbic acid deficiency is responcible for lathyrus toxicity, the effect of dietary feeding of lathyrus pulse in normal and scorbutic guinea pigs for 3 months, on intestinal biochemical parameters was undertaken. Methods The intestinal brush border membrane (BBM) marker and xenobiotic metabolising enzymes (XME) were assayed. Results Exposure to 80% lathyrus alone and in scorbutic conditions showed significant inhibition of alkaline phosphatase (28%-30%), sucrase (19%) and γ-glutamyl transpeptidasc (GGT) (15%-27%)enzymes, while Ca2+-Mg2+-ATPase was significantly inhibited (38%) in scorbutic plus lathyrus treated group. The phase Ⅰ XME (AHH) remained unchanged while the phase Ⅱ enzyme glutathioneS-tranferase (GST) was significantly decreased (20%-22%) in lathyrus and scorbutic plus lathyrus treated groups. Quinone reductase (QR) activity was found to be significantly decreased in lathyrus exposed group (20%). The intestinal biomarker contents including hexose (25%-34%) and phospholipids (20%-40%) were significantly reduced in lathyrus and scorbutic plus lathyrus exposed animals, while sialic acid showed a significant decrease (28%) in scorbutic plus lathyrus treated group. However, cholesterol levels were signifcantly enhanced (15%-28%) in lathyrus and scorbutic plus lathyrus treated animals. Conclusion The results indicate that oral feeding of lathyrus pulse to guinea pigs can alter BBM parameters as well as XME, which may result in the intestinal toxicity.Further, ascorbic acid deficiency could be one of the pre-disposing factors of lathyrus toxicity.     

Impact of lead stress and adaptation in Escherichia coli

The growth rate of Escherichia coli was stimulated when cells were in media containing lead up to a concentration of 300 ppm. Higher concentrations inhibited growth. Metal analysis revealed that in the presence of lead E. coli concentrates 22.8 mg of lead per gram (dry weight) of cells. Analysis of cellular subfractions indicated that membrane fraction concentrated over 95% of the lead taken up by cells, of which a major portion was found to be associated with membrane lipids. Alterations in alkaline phosphatase, Ca2+-Mg2+ -ATPase activities and the carbohydrate and phospholipid contents in membrane fractions were also observed when cells were grown in the presence of lead. A time- and concentration-dependent increase in the release of carbohydrates by the cells was also evident. The results suggest that besides thriving in higher lead surroundings, E. coli possess a marked ability to concentrate substantial amount of inorganic lead.     

Safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally active novel camptothecin analog, DRF-1042, in refractory cancer patients in a phase I dose escalation study

The objective of this study was to characterize the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and antitumor effects of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given for 5 consecutive days for 2 weeks, repeated every 3 weeks at 1.5 to 270 mg/m(2). Adverse events were monitored following NCI-CTC. Pharmacokinetics of lactone and total forms were determined using validated high-performance liquid chromatography (HPLC) and noncompartmental methods. Efficacy was evaluated applying World Health Organization (WHO) criteria. The 1st course was used to determine DLT and MTD. Twenty-five patients received 73 courses of therapy. Myelosuppression and diarrhea were DLTs. MTD was 120 mg/m(2)/day. AUC increased approximately linearly with dose. The t(1/2) for lactone and total forms was 9.9 and 29 hours, respectively. AUCs correlated significantly with nadir leucopenia and grade 4 diarrhea. Two complete responses (CRs) and 2 partial responses (PRs) were observed. In addition, 4 stable diseases were observed. The recommended phase II dose is 80 mg/m(2)/day.     

Biochemical toxicology of argemone oil. I. Effect on hepatic cytochrome P-450 and xenobiotic metabolizing enzymes

The in vivo effect of argemone oil on hepatic xenobiotic metabolizing enzymes was investigated in albino rats following either a single (10 ml kg-1 body wt.) or multiple intraparenteral doses (5 ml kg-1 body wt.) for three days. Animals sacrificed 72 h after a single intraparenteral dose of argemone oil exhibited a significant loss of hepatic cytochrome P-450 (35%) and cytochrome b5 (34%) contents and inhibition of aminopyrine-N-demethylase (APD), aryl hydrocarbon hydroxylase (AHH) and ethoxycoumarin-O-deethylase (ECD) activities (21-39%). Three successive 24-hourly intraparenteral injections of argemone oil followed by sacrificing the animals after 24 h of the last injection, showed a greater degree of inhibition of the content of cytochrome P-450 (58%) and its dependent mixed-function oxidases (35-63%). Also, multiple treatment of argemone oil caused a depletion of endogenous hepatic glutathione (GSH) content (72%) with a concomitant increase in lipid peroxidation (177%) and decrease in glutathione-S-transferase (GST) activity (30%). A significant decrease in relative liver weight (39%) was observed in animals treated with multiple treatment of argemone oil. These results suggest that argemone oil can alter both membrane and cytosolic defences and destabilizes the hepatic cytochrome P-450 dependent mixed-function oxidase system, so that it tips in the direction of autooxidative peroxidation of lipids.