DNA adduct formation and oxidative stress in colon and liver of Big Blue rats after dietary exposure to diesel particles

Exposure to diesel exhaust particles (DEP) via the gastrointestinal route may impose risk of cancer in the colon and liver. We investigated the effects of DEP given in the diet to Big Blue rats by quantifying a panel of markers of DNA damage and repair, mutation, oxidative damage to proteins and lipids, and antioxidative defence mechanisms in colon mucosa cells, liver tissue and the blood compartment. Seven groups of rats were fed a diet with 0, 0.2, 0.8, 2, 8, 20 or 80 mg DEP/kg feed for 21 days. DEP induced a significant increase in DNA strand breaks in colon and liver. There was no effect on oxidative DNA damage (8-oxodG) in colon or liver DNA or in the urine. However, the mRNA expression of OGG1, encoding an enzyme involved in repair of 8-oxodG, was increased by DEP in both liver and colon. DNA adduct levels measured by 32P-post-labelling were elevated in colon and liver, and the expression of ERCC1 gene was affected in liver, but not in colon. In addition to these effects, DEP exposure induced apoptosis in liver. There was no significant change in mutation frequency in colon or liver. The levels of oxidative protein modifications (oxidized arginine and proline residues) were increased in liver accompanied by enhanced vitamin C levels. In plasma, we found no significant effects on oxidative damage to proteins and lipids, antioxidant enzymes or vitamin C levels. Our data indicate that gastrointestinal exposure to DEP induces DNA adducts and oxidative stress resulting in DNA strand breaks, enhanced repair capacity of oxidative base damage, apoptosis and protein oxidation in colon mucosa cells and liver.     

Compensation claims after knee arthroplasty surgery in Norway 2008–2018

Background and purpose — Orthopedic surgery is one of the specialties with most compensation claims. We assessed the claims following knee arthroplasty surgery reported to the Norwegian System of Patient Injury Compensation (NPE) in light of institutional procedure volume.Patients and methods — We collected data from NPE and the Norwegian Arthroplasty Register (NAR) for the study period (2008–2018). Age, sex, type of claim, and reason for compensation were collected from NPE, while the number of arthroplasty surgeries was collected from NAR. The treating hospitals were grouped by quartiles according to annual procedure volume. The effect of hospital volume on the likelihood of an accepted claim was estimated.Results — NAR received 64,241 reports of arthroplasty procedures, of which 572 (0.9%) patients filed a claim for treatment injury. 55% of the claims were accepted, representing 0.5% of all knee arthroplasties. The most common reason for accepted claim was a hospital-acquired infection, in 28% of the patients, followed by misplaced implant (26%) and aseptic loosening (13%). The hospitals with the lowest annual volume (57 or fewer arthroplasties per year, first quarter) had a statistically significantly larger fraction of granted claims per procedures compared with other institutions.Interpretation — The overall risk of ending up with compensation due to treatment error following knee arthroplasty was 0.5%. The risk of accepted claim was greater for patients operated in the lowest volume hospitals.

The number of knee arthroplasty procedures in Norway has increased over the last decade and is now over 7,000 per year (Ackerman et al. 2017, NAR 2020). About 1 in 5 patients receiving a TKA remains dissatisfied with the result (Gunaratne et al. 2017). Although serious complications are rare, infections, implant loosening, misplaced implants, residual pain, and other complications do occur, with potential detrimental results. To monitor the safety of implants and define the epidemiology of the procedures, the Norwegian Arthroplasty Register (NAR) was established in 1987 (Havelin et al. 2000). NAR provides a comprehensive overview of knee arthroplasties taking place in Norway. Compliance with the registry is 97.6% for primary TKA and 93.2% for revisions (Wiik 2014).Patients who suffer an injury while receiving health services, within either the public or the private healthcare sector, can file a claim with the Norwegian System of Patient Injury Compensation (NPE). 3 criteria must be fulfilled for a claim to be accepted:

1. The injury must have been caused during health services (diagnosis, examination, treatment, care, or lack of such), even if no one is to blame. If the injury is severe and unexpected, compensation may be awarded even where no error or omission in treatment has occurred (for example if infection occurs despite adequate prophylaxis).
2. The injury must have caused financial loss to the patient, except if the injury leads to permanent medical impairment of more than 15%, in which case compensation might be awarded despite financial loss. This might be relevant for retired patients or for patients who can continue to work in spite of the disability.
3. The patient must file a claim within a reasonable time (currently set at 3 years) after the patient realizes that the injury is caused by the treatment or lack of treatment received. The claim is filed with NPE at no cost to the patient.

There is compelling evidence that low surgical volume increases the risk of complications and revision after knee arthroplasty surgery (Jaeschke et al. 1989, Badawy et al. 2013, Pamilo et al. 2015, Badawy et al. 2017). Whether this association is also true for injury compensation has not been studied. We evaluated the claims following primary and revision knee arthroplasty surgery filed with NPE and compared the findings with the results from NAR with a focus on annual hospital procedure volume.     

The selective dopamine D2 receptor antagonist raclopride discriminates between dopamine-mediated motor functions

The actions on central dopamine (DA) mechanisms of raclopride, a new substituted benzamide, were studied by means of behavioural and biochemical methods in the rat. Raclopride blocked the in vitro binding of the dopamine D₂ antagonist ³H-spiperone (IC₅₀=32 nM), but not of the unselective D₁ antagonist ³H-flupenthixol (IC₅₀>100,000 nM) in rat striatum, and failed to inhibit striatal DA-sensitive adenylate cyclase in vitro (IC₅₀>100,000 nM). Raclopride caused a dose-dependent increase in the DA metabolites HVA and DOPAC in the striatum and olfactory tubercle. Behavioural studies showed that raclopride discriminates between the motor behaviours induced by the DA agonist apomorphine. Thus, unlike haloperidol, raclopride blocked apomorphine-induced hyperactivity at considerably lower doses than those inhibiting oral stereotypies. Moreover, raclopride showed a high separation between the doses for blockade of apomorphine-induced hyperactivity and those inducing catalepsy in rats. Raclopride caused a dose-dependent blockade of the specific binding of ³H-spiperone and ³H-N-n-propylnorapomorphine (³H-NPA) in vivo at doses similar to those blocking the behavioural effects of apomorphine. The maximal blockade of ³H-spiperone binding in vivo was lower for raclopride than for haloperidol. Raclopride caused a greater inhibition of ³H-NPA than of ³H-spiperone in vivo binding in the striatum. It is suggested that the ability of raclopride to discriminate between different DA-mediated functions may be attributed to a preferential blockade of a subclass of functionally coupled dopamine D₂ receptors in striatal as well as in extrastriatal brain regions in the rat.     

Progression of meniscal degenerative changes in college football players: evaluation with MR imaging

Intrameniscal degenerative changes, presumably due to mild repetitive trauma, have been shown in many college and professional athletes, but it is uncertain over what period of time they can develop or significantly progress. To ascertain this period, the authors used magnetic resonance (MR) imaging to examine one knee in each of 20 players in the starting lineup of a major college football team before and after the season. Only asymptomatic knees (right, n = 10; left, n = 10) were examined; the images were reviewed blindly by one experienced observer without reference to the other examination. A significant progression existed in the grade of signal intensity shown in the menisci over the course of the season (P less than .001). Although this is a small study covering only 1 year, these preliminary results suggest that significant degeneration can occur in the menisci of asymptomatic players over a single season.     

Temperature Changes During Ultrasonic Irrigation with Different Inserts and Modes of Activation

This study evaluated temperature changes during passive ultrasonic irrigation. Root canals of three extracted maxillary canines were enlarged to size #45. Thermocouples were mounted 3, 6, and 9 mm from the apical foramen. Teeth were placed in a water bath at 37°C. Distilled water (20°C) was continuously delivered through an ultrasonic unit (group 1) or deposited into the root canal before ultrasonic activation (group 2); for activation, noncutting nickel-titanium (NiTi) inserts or stainless steel K-files #15, #25, and #35 were used. Before and during ultrasonic activation, temperatures were continuously measured for 210 seconds. Statistical analysis was performed using analysis of variance and Scheffé post hoc tests. Temperatures initially decreased by up to 7.4°C; these drops were significantly smaller in group 1 than in group 2 (p < 0.001) in the middle and apical root canal third. The decreases were followed by temperature rises for all inserts in group 2. However, in group 1, temperatures just reached baseline values in middle and apical thirds; in the coronal root canal third, lower temperatures were measured. In group 2, mean temperature rises were 7.7°, 7.5°, and 4.2°C in coronal, middle, and apical root canal thirds. Here, K-file type inserts size #35 generated highest and inserts size #15 the lowest temperatures rises; NiTi inserts were more effective than size #15 K-files and less effective than #35 K-files. Continuous flow negated the potential of ultrasonic activation to heat irrigation solutions. Noncutting NiTi instruments and large K-files were more effective than small K-files in warming deposited irrigants.