Uptake, distribution and elimination of palladium-doped polystyrene nanoplastics in rainbow trout (Oncorhynchus mykiss) following dietary exposure.

The ingestion of nanoplastics (NPs) by fish has led to concerns regarding fish health and food chain transfer, but analytical constraints have hindered quantitative data collection on their uptake and depuration. We used palladium-doped polystyrene nanoplastics (PS-Pd NPs, ~200 nm) to track particle fate in rainbow trout (Oncorhynchus mykiss) during a week-long dietary exposure and subsequent 7-day depuration period on a control diet (no added PS-Pd NPs). At Day 3 and 7 of the exposure, and after depuration, the mid intestine, hind intestine, liver, gallbladder, kidney, gill and carcass were sampled. All organs and the carcass were analysed for total Pd content by inductively couple plasma mass spectrometry. After 3 days of exposure, the mid (32.5 ± 8.3 ng g-1) and hind (42.3 ± 8.2 ng g-1) intestine had significantly higher total Pd concentrations compared to the liver and carcass (1.3 ± 0.4 and 3.4 ± 1.1 ng g-1, respectively). At Day 7, there was no time-related difference in any organ (or the carcass) total Pd concentrations compared to Day 3. When the total Pd content was expressed as a body distribution based on mass of tissue, the carcass contained the highest fraction with 72.5 ± 5.2 % at Day 7, which could raise concerns over transfer to higher trophic levels. The total number of particles that entered the fish over the 7 days was 94.5 ± 13.5 × 106 particles, representing 0.07 ± 0.01 % of the Pd the fish had been fed. Following depuration, there was no detectable Pd in any organ or the carcass, indicating clearance from the fish. These data indicate that these NPs are taken into the internal organs and carcass of fish, yet removal of the exposure results in substantial excretion to below the limit of detection

Differences in need for antihypertensive drugs among those aware and unaware of their hypertensive status: a cross sectional survey

BACKGROUND: Lack of antihypertensive use among hypertensive individuals is a major public health problem. It remains unclear as to how much of this lack of treatment is because of failure to diagnose hypertension or failure to initiate drug treatment for those with a diagnosis of hypertension. The primary aim of this study was to determine the proportion of those untreated individuals who would be recommended to start drug therapy for control of blood pressure among those aware or unaware of their diagnosis of hypertension. METHODS: The Canadian Heart Health Surveys (1986 – 1992), a national, cross-sectional descriptive survey (n = 23 129), was used to determine the proportion of individuals who were untreated, yet satisfied the 2004 Canadian hypertension guidelines for initiating drug therapy. Patients were divided into subgroups of those aware and unaware of having a diagnosis of hypertension according to self reported awareness from the survey. RESULTS: Of those with untreated hypertension (= 140/90 mmHg), only 37% were aware of their diagnosis. 74% of untreated individuals aware of their diagnosis of hypertension would require drug therapy, compared to 57% of those who were unaware. Of those >65 years of age, 52% of aware individuals needed drug therapy whereas only 34% of unaware elderly would need drug treatment. CONCLUSION: In both unaware and aware subgroups, the majority of patients with untreated hypertension would benefit from antihypertensive drug therapy according to the 2004 Canadian Hypertension recommendations. The proportion of untreated patients that still need drug therapy was higher among those who were aware compared to those who were unaware. This finding suggests that the major gap in hypertension control may be in initiating drug therapy rather than in diagnosing hypertension. Further studies are needed to confirm these results to ultimately help strategize public health efforts in controlling hypertension

Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney

BACKGROUND: The role of cyclooxygenase(COX)-1 and COX-2 in the saluretic and renin-angiotensin responses to loop diuretics in the cat is unknown. We propose in vivo characterisation of isoform roles in a furosemide model by administering non-steroidal anti-inflammatory drugs (NSAIDs) with differing selectivity profiles: robenacoxib (COX-2 selective) and ketoprofen (COX-1 selective). RESULTS: In this four period crossover study, we compared the effect of four treatments: placebo, robenacoxib once or twice daily and ketoprofen once daily concomitantly with furosemide in seven healthy cats. For each period, urine and blood samples were collected at baseline and within 48 h of treatment starting. Plasma renin activity (PRA), plasma and urinary aldosterone concentrations, glomerular filtration rate (GFR) and 24 h urinary volumes, electrolytes and eicosanoids (PGE(2), 6-keto-PGF1(α,) TxB(2)), renal injury biomarker excretions [N-acetyl-beta-D-glucosaminidase (NAG) and Gamma-Glutamyltransferase] were measured. Urine volume (24 h) and urinary sodium, chloride and calcium excretions increased from baseline with all treatments. Plasma creatinine increased with all treatments except placebo, whereas GFR was significantly decreased from baseline only with ketoprofen. PRA increased significantly with placebo and once daily robenacoxib and the increase was significantly higher with placebo compared to ketoprofen (10.5 ± 4.4 vs 4.9 ± 5.0 ng ml(−1) h(−1)). Urinary aldosterone excretion increased with all treatments but this increase was inhibited by 75 % with ketoprofen and 65 % with once daily robenacoxib compared to placebo. Urinary PGE(2) excretion decreased with all treatments and excretion was significantly lower with ketoprofen compared to placebo. Urinary TxB(2) excretion was significantly increased from baseline only with placebo. NAG increased from baseline with all treatments. Immunohistochemistry on post-mortem renal specimens, obtained from a different group of cats that died naturally of non-renal causes, suggested constitutive COX-1 and COX-2 co-localization in many renal structures including the macula densa (MD). CONCLUSIONS: These data suggest that both COX-1 and COX-2 could generate the signal from the MD to the renin secreting cells in cats exposed to furosemide. Co-localization of COX isoenzymes in MD cells supports the functional data reported here. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0598-z) contains supplementary material, which is available to authorized users

In situ monitoring the effects of Ti6Al4V powder oxidation during laser powder bed fusion additive manufacturing

Making laser powder bed fusion (L-PBF) additive manufacturing process sustainable requires effective powder recycling. Recycling of Ti6Al4V powder in L-PBF can lead to powder oxidation, however, such impact on laser-matter interactions, process, and defect dynamics during L-PBF are not well understood. This study reveals and quantifies the effects of processing Ti6Al4V powders with low (0.12 wt%) and high (0.40 wt%) oxygen content during multilayer thin-wall L-PBF using in situ high speed synchrotron X-ray imaging. Our results reveal that high oxygen content Ti6Al4V powder can reduce melt ejections, surface roughness, and defect population in the built parts. With increasing oxygen content in the part, there is an increase in microhardness due to solid solution strengthening and no significant change in the microstructure is evident

Demonstrating the translocation of nanoplastics across the fish intestine using palladium-doped polystyrene in a salmon gut-sac

Fish are widely reported to ingest microplastics with low levels accumulating in the tissues, but owing to analytical constraints, much less is known about the potential accumulation of nanoplastics via the gut. Recently, the labelling of plastics with inorganic metals (e.g., palladium) has allowed measurements of nanoplastic uptake. The aim of the current study was to quantitatively assess the uptake of nanoplastics by the fish gut using palladium-doped nanoplastics (with a mean hydrodynamic radius of 202 ± 7 nm). By using an ex vivo gut sac exposure system, we show that in 4 h between 200 and 700 million nanoplastics (representing 2.5–9.4% of the administered nanoplastics dose) can enter the mucosa and muscularis layers of the intestine of salmon. Of the particles taken up, up to 700,000 (representing 0.6% of that taken into the tissue) of the nanoplastics passed across the gut epithelium of the anterior intestine and exit into the serosal saline. These data, generated in highly controlled conditions provide a proof-of-concept study, suggesting the potential for nanoplastics to distribute throughout the body, indicating the potential for systemic exposure in fish.Demonstrating the translocation of nanoplastics across the fish intestine using palladium-doped polystyrene in a salmon gut-sacpublishedVersio

Ethnic disparity in 21-hydroxylase gene mutations identified in Pakistani congenital adrenal hyperplasia patients

Background: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by defects in the steroid 21 hydroxylase gene (CYP21A2). We studied the spectrum of mutations in CYP21A2 gene in a multi-ethnic population in Pakistan to explore the genetics of CAH. Methods: A cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay. Results: Overall, 29 patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females representing all the major ethnic groups of Pakistan. Parental consanguinity was reported in 65% cases and was equally distributed in the major ethnic groups. Among 58 chromosomes analyzed, mutations were identified in 45 (78.6%) chromosomes. The most frequent mutation was I2 splice (27%) followed by Ile173Asn (26%), Arg 357 Trp (19%), Gln319stop, 16% and Leu308InsT (12%), whereas Val282Leu was not observed in this study. Homozygosity was seen in 44% and heterozygosity in 34% cases. I2 splice mutation was found to be associated with SW in the homozygous. The Ile173Asn mutation was identified in both SW and SV forms. Moreover, Arg357Trp manifested SW in compound heterozygous state. Conclusion: Our study showed that CAH exists in our population with ethnic difference in the prevalence of mutations examined

Evaluations of the effect of sodium metabisulfite on the stability and dissolution rates of various model drugs from the extended release polyethylene oxide matrices

Purpose: This study examines the effect of sodium metabisulfite (SMB) as an antioxidant on the stability and release of various model drugs namely propranolol HCl, theophylline and zonisamide from the polyethylene oxide (PEO) tablets. The antioxidant was used to minimise degradation and instability of the manufactured tablets when stored at 40°C (55±5 % RH) over 8 weeks. Method: Multiple batches of tablets weighing 240 mg (50% w/w) with a ratio of 1:1 drug: polymer and 1% (w/w) sodium metabisulfite containing different model drugs and various molecular weights of PEO 750 and 303 were produced. Results: The results indicated that the use of sodium metabisulfite marginally assisted in reducing drug release and degradation via oxidation in propranolol HCl tablets containing both PEO 750 and 303. In the case of poorly and semi-soluble drugs (zonisamide and theophylline) the formulations with both PEO showed entirely superimposable phenomenon and different release profiles compared to control samples (matrices without SMB). DSC study demonstrated the modifications of the polymer due to degradation and observed the effect of SMB on the thermal degradation of the PEO matrices. Conclusion: The use of antioxidant has assisted in retaining the stability of the manufactured tablets with different model drugs especially those with the highly soluble drug that are susceptible to rapid degradation. This has been reflected by an extended release profile of various drugs used at various stages of the storage time up to 8 weeks

Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds

Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferatoractivator receptor (PPAR) a response in rat and human