Chlorpyrifos-induced dysfunction of lipid metabolism is not restored by supplementation of polyunsaturated fatty acids EPA and ARA in Atlantic salmon liver cells

Exposure to contaminants can lead to accumulation of lipids in the liver. This study aimed to examine whether eicosapentaenoic acid (EPA) and arachidonic acid (ARA) supplementation can protect fish cells against the negative impact of chlorpyrifos (CPF). Atlantic salmon hepatocytes were exposed to either 100 μM CPF, 200 μM EPA, 200 μM ARA, or combinations of these for 48 h, and endpoints included lipid droplet formation, gene expression, and global metabolomic analysis. The results showed that polyunsaturated fatty acid (PUFA) supplementation modified the cell lipid composition, reduced uptake of CPF and increased the cellular number and size of lipid droplets. CPF exposure induced the transcription of ppara and fabp3, and reduced the levels of several PUFAs, and lead to accumulation of monoacylglycerols (MAGs) in the cells. Supplementation of EPA or ARA did not prevent CPF-induced accumulation of MAGs and only to a limited degree rescued the response on other lipids. CPF exposure further reduced energy metabolism, a response partly restored by PUFA supplementation. Reduced levels of glutathione indicated oxidative stress; an effect not ameliorated by the PUFAs. Altogether, this study shows that PUFA supplementation only modestly protects Atlantic salmon hepatocytes against the negative impact of CPF.publishedVersio

A cluster randomised controlled trial in primary dental care based intervention to improve professional performance on routine oral examinations and the management of asymptomatic impacted third molars: study protocol

BACKGROUND: Routine oral examination (ROE) refers to periodic monitoring of the general and oral health status of patients. In most developed Western countries a decreasing prevalence of oral diseases underpins the need for a more individualised approach in assigning individualised recall intervals for regular attendees instead of systematic fixed intervals. From a quality-of-care perspective, the effectiveness of the widespread prophylactic removal of mandibular impacted asymptomatic third molars (MIM) in adolescents and adults is also questionable. Data on the effectiveness of appropriate interventions to tackle such problems, and for promoting continuing professional development in oral health care are rare. METHODS/DESIGN: This study is a cluster randomised controlled trial with groups of GDPs as the unit of randomisation. The aim is to determine the effectiveness and efficiency of small group quality improvement on professional decision-making of general dental practitioners (GDPs) in daily practice. Six peer groups ('IQual-groups') shall be randomised either to the intervention arm I or arm II. Groups of GDPs allocated to either of these arms act as each other's control group. An IQual peer group consists of eight to ten GDPs who meet in monthly structured sessions scheduled for discussion on practice-related topics. GDPs in both trial arms receive recently developed evidence-based clinical practice guidelines (CPG) on ROE or MIM. The implementation strategy consists of one interactive IQual group meeting of two to three hours. In addition, both groups of GDPs receive feedback on personal and group characteristics, and are invited to make use of web-based patient risk vignettes for further individual training on risk assessment policy. Reminders (flow charts) will be sent by mail several weeks after the meeting. The main outcome measure for the ROE intervention arm is the use and appropriateness of individualised risk assessment in assigning recall intervals, and for the MIM-intervention group the use and appropriateness of individualised mandibular impacted third molar risk management. Both groups act as each other's control. Pre-intervention data will be collected in study months one through three. Post-intervention data collection will be performed after nine months

Reduction in podocyte density as a pathologic feature in early diabetic nephropathy in rodents: Prevention by lipoic acid treatment

BACKGROUND: A reduction in the number of podocytes and podocyte density has been documented in the kidneys of patients with diabetes mellitus. Additional studies have shown that podocyte injury and loss occurs in both diabetic animals and humans. However, most studies in animals have examined relatively long-term changes in podocyte number and density and have not examined effects early after initiation of diabetes. We hypothesized that streptozotocin diabetes in rats and mice would result in an early reduction in podocyte density and that this reduction would be prevented by antioxidants. METHODS: The number of podocytes per glomerular section and the podocyte density in glomeruli from rats and mice with streptozotocin (STZ)-diabetes mellitus was determined at several time points based on detection of the glomerular podocyte specific antigens, WT-1 and GLEPP1. The effect of insulin administration or treatment with the antioxidant, α-lipoic acid, on podocyte number was assessed. RESULTS: Experimental diabetes resulted in a rapid decline in apparent podocyte number and podocyte density. A significant reduction in podocytes/glomerular cross-section was found in STZ diabetes in rats at 2 weeks (14%), 6 weeks (18%) and 8 weeks (34%) following STZ injection. Similar declines in apparent podocyte number were found in STZ diabetes in C57BL/6 mice at 2 weeks, but not at 3 days after injection. Treatment with α-lipoic acid substantially prevented podocyte loss in diabetic rats but treatment with insulin had only a modest effect. CONCLUSION: STZ diabetes results in reduction in apparent podocyte number and in podocyte density within 2 weeks after onset of hyperglycemia. Prevention of these effects with antioxidant therapy suggests that this early reduction in podocyte density is due in part to increased levels of reactive oxygen species as well as hyperglycemia

Mechanisms of Class II correction induced by the crown Herbst appliance as a single-phase Class II therapy : 1 year follow-up

Background The objective of this study is to evaluate the skeletal and dentoalveolar effects of the crown Herbst appliance used alone for a single phase of therapy followed by a 1-year observation period. Methods Forty patients (mean age 13.6 ± 1.3 years) with a stable Class I occlusion 1 year following the treatment with the crown Herbst appliance were selected from a prospective sample of 180 consecutively treated Class II patients. No other appliances were used during treatment or during the follow-up period. The dentoskeletal changes were compared with a matched sample of untreated Class II subjects (mean age 13.9 ± 1.6 years). Lateral cephalograms were taken before treatment, after Herbst treatment (1 year), and after 1-year follow-up. Overcorrection was avoided intentionally. Results Treatment produced an increase in mandibular length, a decrease in ANB angle, and a restriction in the vertical growth of posterior maxilla. The maxillary molars moved backward and tipped distally. The lower incisors proclined markedly, and the upper incisors became retroclined. During the follow-up period, the changes primarily were dentoalveolar in nature, with marked rebound of the upper molars and lower incisors, resulting in some increases in overbite and overjet. Conclusions The occlusal correction of Class II malocclusion observed 1 year after the crown Herbst appliance as a single-phase therapy was achieved primary due to the dentoalveolar changes and only limited skeletal change occurred.publishersversionPeer reviewe

Correlation between 5-fluorouracil metabolism and treatment response in two variants of C26 murine colon carcinoma

Following an i.p. dose of 150 mg x kg(-1) 5-fluorouracil (5-FU), drug uptake and metabolism over a 2-h period were studied by in vivo (19)F magnetic resonance spectroscopy (MRS) for the murine colon carcinoma lines C26-B (5-FU-insensitive; n=11) and C26-10 (5-FU-sensitive; n=15) implanted s.c. in Balb/C mice. Time courses for tumour growth, intracellular levels of FdUMP, thymidylate synthase (TS) activity, and 5-FU in RNA were also determined, and the effects of a 9.5-min period of carbogen breathing, starting 1 min before drug administration, on MRS-detected 5-FU metabolism and tumour growth curves were examined. Both tumour variants generated MRS-detectable 5-FU nucleotides and showed similar initial growth inhibition after treatment. However, the growth rate of C26-B tumours returned to normal, while the sensitive C26-10 tumours, which produced larger fluoronucleotide pools, still showed moderate growth inhibition. Carbogen breathing did not significantly influence 5-FU uptake or fluoronucleotide production but did significantly enhance growth inhibition in C26-10 tumours. While both tumour variants exhibited incorporation of 5-FU into RNA and inhibition of TS via FdUMP, clearance of 5-FU from RNA and recovery of TS activity were greater for the insensitive C26-B line, indicating that these processes, in addition to 5-FU uptake and metabolism, may be important determinants of drug sensitivity and treatment respons

DIA1R Is an X-Linked Gene Related to Deleted In Autism-1

Background: Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62 % similar overall (28 % identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-lik

A prediction model for underestimation of invasive breast cancer after a biopsy diagnosis of ductal carcinoma in situ: based on 2892 biopsies and 589 invasive cancers

Background: Patients with a biopsy diagnosis of ductal carcinoma in situ (DCIS) might be diagnosed with invasive breast cancer at excision, a phenomenon known as underestimation. Patients with DCIS are treated based on the risk of underestimation or progression to invasive cancer. The aim of our study was to expand the knowledge on underestimation and to develop a prediction model. Methods: Population-based data were retrieved from the Dutch Pathology Registry and the Netherlands Cancer Registry for DCIS between January 2011 and June 2012. Results: Of 2892 DCIS biopsies, 21% were underestimated invasive breast cancers. In multivariable analysis, risk factors were high-grade DCIS (odds ratio (OR) 1.43, 95% confidence interval (CI): 1.05–1.95), a palpable tumour (OR 2.22, 95% CI: 1.76–2.81), a BI-RADS (Breast Imaging Reporting and Data System) score 5 (OR 2.36, 95% CI: 1.80–3.09) and a suspected invasive component at biopsy (OR 3.84, 95% CI: 2.69–5.46). The predicted risk for underestimation ranged from 9.5 to 80.2%, with a median of 14.7%. Of the 596 invasive cancers, 39% had unfavourable features. Conclusions: The risk for an underestimated diagnosis of invasive breast cancer after a biopsy diagnosis of DCIS is considerable. With our prediction model, the individual risk of underestimation can be calculated based on routinely available preoperatively known risk factors (https://www.evidencio.com/models/show/1074)

Chlorpyrifos-induced dysfunction of lipid metabolism is not restored by supplementation of polyunsaturated fatty acids EPA and ARA in Atlantic salmon liver cells

Exposure to contaminants can lead to accumulation of lipids in the liver. This study aimed to examine whether eicosapentaenoic acid (EPA) and arachidonic acid (ARA) supplementation can protect fish cells against the negative impact of chlorpyrifos (CPF). Atlantic salmon hepatocytes were exposed to either 100 μM CPF, 200 μM EPA, 200 μM ARA, or combinations of these for 48 h, and endpoints included lipid droplet formation, gene expression, and global metabolomic analysis. The results showed that polyunsaturated fatty acid (PUFA) supplementation modified the cell lipid composition, reduced uptake of CPF and increased the cellular number and size of lipid droplets. CPF exposure induced the transcription of ppara and fabp3, and reduced the levels of several PUFAs, and lead to accumulation of monoacylglycerols (MAGs) in the cells. Supplementation of EPA or ARA did not prevent CPF-induced accumulation of MAGs and only to a limited degree rescued the response on other lipids. CPF exposure further reduced energy metabolism, a response partly restored by PUFA supplementation. Reduced levels of glutathione indicated oxidative stress; an effect not ameliorated by the PUFAs. Altogether, this study shows that PUFA supplementation only modestly protects Atlantic salmon hepatocytes against the negative impact of CPF

Chlorpyrifos-induced dysfunction of lipid metabolism is not restored by supplementation of polyunsaturated fatty acids EPA and ARA in Atlantic salmon liver cells

Exposure to contaminants can lead to accumulation of lipids in the liver. This study aimed to examine whether eicosapentaenoic acid (EPA) and arachidonic acid (ARA) supplementation can protect fish cells against the negative impact of chlorpyrifos (CPF). Atlantic salmon hepatocytes were exposed to either 100 μM CPF, 200 μM EPA, 200 μM ARA, or combinations of these for 48 h, and endpoints included lipid droplet formation, gene expression, and global metabolomic analysis. The results showed that polyunsaturated fatty acid (PUFA) supplementation modified the cell lipid composition, reduced uptake of CPF and increased the cellular number and size of lipid droplets. CPF exposure induced the transcription of ppara and fabp3, and reduced the levels of several PUFAs, and lead to accumulation of monoacylglycerols (MAGs) in the cells. Supplementation of EPA or ARA did not prevent CPF-induced accumulation of MAGs and only to a limited degree rescued the response on other lipids. CPF exposure further reduced energy metabolism, a response partly restored by PUFA supplementation. Reduced levels of glutathione indicated oxidative stress; an effect not ameliorated by the PUFAs. Altogether, this study shows that PUFA supplementation only modestly protects Atlantic salmon hepatocytes against the negative impact of CPF

Routine oral examination: differences in characteristics of Dutch general dental practitioners related to type of recall interval.

Contains fulltext : 48541.pdf (publisher's version ) (Closed access)OBJECTIVES: The aim of this study was to explore differences in behaviour (characteristics and opinions) among general dental practitioners (GDPs), using either a fixed (Fx) or an individualized recall interval (Iv) between successive routine oral examinations (ROEs). METHODS: In the year 2000, data were collected by means of a written questionnaire sent to a random stratified sample of 610 dentists of whom 521 responded, of which 508 (83%) were used for analysis. RESULTS: Two groups of GDPs were distinguished based on their answer to the question: 'Do you apply for all patients a fixed recall interval between two successive ROEs?' Fifty-one per cent of the GDPs (n=257) applied Fxs for all patients, generally for a period of 6 months. Ivs were applied by 49% (n=251) of GDPs, depending on the determination of specific patient characteristics. Logistic regression analysis showed that GDPs applying Fxs also used fixed periods between successive bitewing radiographs for all patients. Furthermore, dentists applying Ivs required more time to conduct an ROE, partly because of a more extensive periodontal screening. GDPs applying Fxs, adhered more to the opinion that a fixed recall regime (every 6 months, as existed before 1995) should be re-introduced, whereas the GDPs in support of Ivs were more in favour to support the opinion that the ROE is 'an excellent instrument for effective, individualized oral care'. CONCLUSIONS: Dutch GDPs differ in the way they deal with the determination of recall interval frequency. These are also specific differences in performance and opinions regarding ROE. With the changing prevalence of oral diseases and the skewed distribution within populations, further research is advocated on consistent decision making to determine the most appropriate recall policy in preventing oral disease