PLOD2 gene expression in infrapatellar fat pad is correlated with fat mass in obese patients with end-stage knee osteoarthritis.

Objective: To investigate associations between obesity-linked systemic factors and gene expression indicative for the inflammatory and fibrotic processes in the infrapatellar fat pad (IFP), in a population of obese patients with end-stage knee osteoarthritis (KOA). Methods: We collected human IFPs from 48 patients with a mean body mass index (BMI) of 35.44 â€‹kg/m2 during total knee replacement procedures. These patients were part of a randomized controlled trial and met the criteria of having OA and a BMI of ≥30 â€‹kg/m2. Blood samples were collected to assess serum levels of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and leptin. Total body composition was measured using dual-energy X-ray absorptiometry. Gene expressions of IL6, TNFA, COL1A1, IL1B, ASMA, PLOD2 in the IFP were analyzed. Results: Univariate analysis resulted in a positive correlation between BMI and procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) expression (r2 â€‹= â€‹0.13). In univariate analyses of obesity-linked systemic factors and PLOD2, significant correlations were found for lean mass (r2 â€‹= â€‹0.20), fat mass (r2 â€‹= â€‹0.20), serum cholesterol (r2 â€‹= â€‹0.17), serum triglycerides (r2 â€‹= â€‹0.19) and serum leptin (r2 â€‹= â€‹0.10). A multiple linear regression model indicated fat mass to be a strong predictor of PLOD2 production in the IFP (r2 â€‹= â€‹0.22, P â€‹= â€‹0.003). Conclusion: Our study demonstrates the positive association between fat mass and PLOD2 expression in the IFP of obese end-stage knee OA patients. This may indicate that within this patient population the fibrotic process in the IFP is influenced by systemic adipose tissue, next to local inflammatory processes.

Limited use of local anesthesia for open inguinal hernia repair: a qualitative study.

PURPOSE: Local anesthesia for open inguinal hernia repair is recommended by guidelines but is rarely used in clinical practice in several countries. This study aimed to explore physician's considerations in choosing type of anesthesia and barriers for implementing local anesthesia for open hernia repair in clinical practice. METHODS: We performed individual semi-structured interviews of surgeons and anesthesiologists. Transcribed data were condensed, coded, categorized, and formulated into themes in an inductive qualitative content analysis. RESULTS: Twenty two participants from seven public hospitals were included in the study. Participants described a standardized setup for general anesthesia with use of intravenous propofol/remifentanil and a laryngeal mask and were generally satisfied with this setup. Their considerations in choosing anesthesia could be described in four themes: (1) Intraoperative pain and quality of surgical technique, (2) Communication and teaching, (3) Logistics, and (4) Clinical routines. CONCLUSION: Participants considered intraoperative pain and quality of surgical technique, communication and teaching, logistics, and clinical routines as important factors when choosing anesthesia for open inguinal hernia repair and these factors acted as barriers for implementing of local anesthesia in Danish public hospitals. In this setting, implementation strategies should, therefore, be multimodal to address these barriers. The potential workload in such an effort should be justified by evidence supporting specific types of local anesthesia comapared with general anesthesia with use of propofol/remifentanil and a laryngeal mask.

Weight Loss Intervention Before Total Knee Replacement: A 12-Month Randomized Controlled Trial.

BACKGROUND AND AIMS: Obesity is an increasing problem in patients after total knee replacement. The aim of this study was to investigate whether a weight loss intervention before primary total knee replacement would improve quality of life, knee function, mobility, and body composition 1 year after surgery. MATERIAL AND METHODS: Patients scheduled for total knee replacement due to osteoarthritis of the knee and obesity were randomized to a control group receiving standard care or to an intervention group receiving 8-week low-energy diet before total knee replacement. Patient-reported quality of life, 6-Min Walk Test, and body composition by dual-energy X-ray absorptiometry were assessed before intervention for the diet group, and within 1 week preoperatively for both groups, and the changes in outcome from baseline to 1 year after total knee replacement were compared between groups. The number of participants was lower than planned, which might introduce a type-2 error and underestimate the trend for a better outcome after weight loss. RESULTS: The analyses are based on a total of 76 patients, 38 in each group. This study showed major improvement in both study groups in quality of life and knee function, though no statistically significant differences between the groups were observed 1 year after total knee replacement. The average weight loss after 8-week preoperative intervention was 10.7 kg and consisted of a 6.7 kg reduction in fat mass. One year after total knee replacement, the participants in the diet group managed to maintain the weight reduction, whereas there was no change in the control group. CONCLUSION: The results suggest that it is feasible and safe to implement an intensive weight loss program shortly before total knee replacement. The preoperative intervention resulted in a 10% body weight loss, improved body composition, lower cardiovascular risk factors, and sustained s-leptin.

Hyperoxia improves autonomic function in individuals with long-duration type 1 diabetes and macroalbuminuria.

AIM: Acute oxygen inhalation and slow deep breathing improve measures of autonomic function transiently in individuals with short-duration type 1 diabetes. Our aims were to examine these interventions and changes in autonomic function in individuals with long-duration type 1 diabetes and to explore interactions with the presence of macroalbuminuria or existing cardiovascular autonomic neuropathy. METHODS: Individuals with type 1 diabetes (n = 54) were exposed to acute oxygen inhalation, slow deep breathing and a combination of both (hereafter 'the combination'). Primary outcomes were change in baroreflex sensitivity and heart rate variability. Associations between changes in outcomes were evaluated using mixed effects models. RESULTS: Mean age ± sd was 60 ± 10 years and diabetes duration was 38 ± 14 years. Changes are presented as per cent difference from baseline with 95% confidence intervals. Acute oxygen inhalation, slow deep breathing and the combination increased baroreflex sensitivity by 21 (10, 34)%, 32 (13, 53)% and 30 (10, 54)%, respectively. Acute oxygen inhalation trended towards increasing heart rate variability 8 (-1, 17)% (P = 0.056), and slow deep breathing and the combination increased heart rate variability by 33 (18, 49)% and 44 (27, 64)% respectively. Macroalbuminuria or cardiovascular autonomic neuropathy did not modify results. CONCLUSION: Autonomic function is improved transiently in individuals with long-duration type 1 diabetes and normoalbuminuria or macroalbuminuria by acute oxygen inhalation and slow deep breathing. There is a risk of survival bias. Autonomic dysfunction might be a reversible condition, and hypoxia might represent a target of intervention.

Prophylactic incisional negative pressure wound therapy reduces the risk of surgical site infection after caesarean section in obese women: a pragmatic randomised clinical trial.

OBJECTIVE: To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section. DESIGN: Multicentre randomised controlled trial. SETTING: Five hospitals in Denmark. POPULATION: Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2 ) undergoing elective or emergency caesarean section. METHOD: The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention-to-treat. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health-related quality of life. RESULTS: Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30-0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups. CONCLUSION: Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section. TWEETABLE ABSTRACT: RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.

Tracking of bone mass from childhood to puberty: a 7-year follow-up. The CHAMPS study DK.

Bone mass in childhood is highly influenced by puberty. At the same age, bone mass was higher for pubertal than pre-pubertal children. A high level of tracking during 7 years from childhood through puberty was shown, indicating that early levels of bone mass may be important for later bone health. INTRODUCTION: Bone mass development in childhood varies by sex and age, but also by pubertal stage. The objectives of this study were to (1) describe bone mass development in childhood as it relates to pubertal onset and to (2) determine the degree of tracking from childhood to adolescence. METHODS: A longitudinal study with 7 years of follow-up was initiated in 2008 to include 831 children (407 boys) aged 8 to 17 years. Participants underwent whole body dual-energy X-ray absorptiometry (DXA) scanning, blood collection to quantify luteinizing hormone levels, and Tanner stage self-assessment three times during the 7-year follow-up. Total body less head bone mineral content, areal bone mineral density, and bone area were used to describe development in bone accrual and to examine tracking over 7 years. RESULTS: Bone mass in pubertal children is higher than that of pre-pubertal children at the same age. Analysing tracking with quintiles of bone mass Z-scores in 2008 and 2015 showed that more than 80% of participants remained in the same or neighbouring quintile over the study period. Tracking was confirmed by correlation coefficients between Z-scores at baseline and 7-year follow-up (range, 0.80-0.84). CONCLUSIONS: Bone mass is highly influenced by pubertal onset, and pubertal stage should be considered when examining children's bone health. Because bone mass indices track from childhood into puberty, children with low bone mass may be at risk of developing osteoporosis later in life.

Shift work at young age is associated with increased risk of multiple sclerosis in a Danish population.

BACKGROUND: Epidemiological studies suggest an important role for environmental factors in developing multiple sclerosis (MS). Furthermore several studies have indicated that the effect of environmental factors may be especially pronounced in adolescents. Recently only one study investigated and found that shift work at young age is associated with an increased risk of developing MS. In this study we focused on the effect of shift work in the vulnerable period between 15-19 years. OBJECTIVE: The aim of this study was to investigate the association between shift work at young age and the risk of developing MS. METHODS: We performed a large case-control study including 1723 patients diagnosed with MS and 4067 controls. MS patients were recruited from the Danish Multiple Sclerosis Biobank and controls from The Danish Blood Donor Study. Information on working patterns and lifestyle factors was obtained using a comprehensive lifestyle-environmental factor questionnaire with participants enrolled between 2009 and 2014. Logistic regression models were used to investigate the association between shift work at age 15-19 years and the subsequent risk of MS and were controlled for effects due to established MS risk factors. RESULTS: We found a statistically significant association when total numbers of night shifts were compared with non-shift workers. For every additional 100 night shifts the odds ratio (OR) for MS was 1.20 (95% confidence interval (CI), 1.08-1.34, p=0.001). Increasing intensity of shift work also increased MS risk. For every additional night per month the OR was 1.04 (95% CI, 1.01-1.06, p=0.002). Duration of shift work in years was not associated with risk of MS. CONCLUSION: This study supports a statistically significant association between shift work at age 15-19 years and MS risk.

Are Danish doctors comfortable teaching in English?

BACKGROUND: From 2012-2015, the Departments of Obstetrics and Gynecology and of Pediatrics at the University of Copenhagen conducted a project, "Internationalization at Home ", offering clinical teaching in English. The project allowed international students to work with Danish speaking students in a clinical setting. Using semi-quantitative questionnaires to 89 clinicians about use of English and need for training, this paper considers if Danish clinical doctors are prepared to teach in English. RESULTS: The majority self-assessed their English proficiency between seven and eight on a 10 unit visual analogue scale, with 10 equivalent to working in Danish, while 15 % rated five or less. However, one-fourth found teaching and writing in English to be twice as difficult than in Danish, and 12 % rated all teaching tasks in English at four or less compared to Danish. The self-assessed need for additional English skills was perceived low. CONCLUSION: Teaching in English was rated as 30 % more difficult than in Danish, and a significant subgroup of doctors had difficulties in all forms of communication in English, resulting in challenges when introducing international students in non-native English speaking medical departments.

Glutamate dysregulation in the trigeminal ganglion: a novel mechanism for peripheral sensitization of the craniofacial region.

In the trigeminal ganglion (TG), satellite glial cells (SGCs) form a functional unit with neurons. It has been proposed that SGCs participate in regulating extracellular glutamate levels and that dysfunction of this SGC capacity can impact nociceptive transmission in craniofacial pain conditions. This study investigated whether SGCs release glutamate and whether elevation of TG glutamate concentration alters response properties of trigeminal afferent fibers. Immunohistochemistry was used to assess glutamate content and the expression of excitatory amino acid transporter (EAAT)1 and EAAT2 in TG sections. SGCs contained glutamate and expressed EAAT1 and EAAT2. Potassium chloride (10 mM) was used to evoke glutamate release from cultured rat SGCs treated with the EAAT1/2 inhibitor (3S)-3-[[3-[[4-(trifluoromethyl)ben zoyl]amino]phenyl]methoxy]-L-aspartic acid (TFB-TBOA) or control. Treatment with TFB-TBOA (1 and 10 µM) significantly reduced the glutamate concentration from 10.6 ± 1.1 to 5.8 ± 1.4 µM and 3.0 ± 0.8 µM, respectively (p<0.05). Electrophysiology experiments were conducted in anaesthetized rats to determine the effect of intraganglionic injections of glutamate on the response properties of ganglion neurons that innervated either the temporalis or masseter muscle. Intraganglionic injection of glutamate (500 mM, 3 µl) evoked afferent discharge and significantly reduced muscle afferent mechanical threshold. Glutamate-evoked discharge was attenuated bythe N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovalerate (APV) and increased by TFB-TBOA, whereas mechanical sensitization was only sensitive to APV. Antidromic invasion of muscle afferent fibers by electrical stimulation of the caudal brainstem (10 Hz) or local anesthesia of the brainstem with lidocaine did not alter glutamate-induced mechanical sensitization. These findings provide a novel mechanism whereby dysfunctional trigeminal SGCs could contribute to cranial muscle tenderness in craniofacial pain conditions such as migraine headache.

Exercise and relaxation intervention for patients with advanced lung cancer: a qualitative feasibility study.

Lung cancer patients experience loss of physical capacity, dyspnea, pain, reduced energy and psychological distress. The aim of this study was to explore feasibility, health benefits and barriers of exercise in former sedentary patients with advanced stage lung cancer, non-small cell lung cancer (NSCLC) (III-IV) and small cell lung cancer (SCLC) (ED), undergoing chemotherapy. The intervention consisted of a hospital-based, supervised, group exercise and relaxation program comprising resistance-, cardiovascular- and relaxation training 4 h weekly, 6 weeks, and a concurrent unsupervised home-based exercise program. An explorative study using individual semi-structured interviews (n=15) and one focus group interview (n=8) was conducted among the participants. Throughout the intervention the patients experienced increased muscle strength, improvement in wellbeing, breathlessness and energy. The group exercise and relaxation intervention showed an adherence rate of 76%, whereas the patients failed to comply with the home-based exercise. The hospital-based intervention initiated at time of diagnosis encouraged former sedentary lung cancer patients to participation and was undertaken safely by cancer patients with advanced stages of disease, during treatment. The patients experienced physical, functional and emotional benefits. This study confirmed that supervised training in peer-groups was beneficial, even in a cancer population with full-blown symptom burden and poor prognosis.

13Carbon and 15nitrogen isotopes in autopsy liver tissue samples from Greenlandic Inuit and Danes: consumption of marine versus terrestrial food.

BACKGROUND/OBJECTIVES: The content of (13)C and (15)N isotopes is higher in marine than in terrestrial food. (13)C and (15)N in human tissue therefore reflects the relative proportions of marine and terrestrial food consumed by the individual. The objective of this study was to measure (13)C and (15)N in liver tissue from Greenlandic Inuit and Danes. SUBJECTS/METHODS: Normal liver tissue was obtained at autopsy in 1992-1994 from 60 Inuit with a median age of 61 years (range 25-83) and in 1986 from 15 ethnic Danes with a median age of 84 years (range 66-93). By sieving, liver tissue was separated in a 'cellular fraction' and a 'connective tissue fraction'. (13)C and (15)N in dry liver tissue was measured on a mass spectrometer. delta(13)C indicates the (13)C content relative to the IAEA-CH-6 reference standard. delta(15)N indicates (15)N content relative to the atmospheric nitrogen reference standard. RESULTS: Inuit: median delta(13)C was -21.2 per thousand in cellular and -20.0 per thousand in connective tissue fractions (P=0.001). Median delta(15)N was 10.6 per thousand in both cellular and connective tissue fractions. Body mass index was negatively correlated with delta(13)C in the connective tissue fraction (r(s)=-0.42, P=0.057). Danes: median delta(13)C was -27.0 per thousand in cellular and -24.3 per thousand in connective tissue fractions (P=0.11). Median delta(15)N was 9.5 per thousand in cellular and 8.9 per thousand in connective tissue fractions (P=0.5). Inuit had higher delta(13)C than Danes in both cellular and connective tissue fractions (P<0.001) as well as higher delta(15)N in the cellular fraction (P=0.01). CONCLUSIONS: Inuit showed considerable variation in the ratio between marine and terrestrial food consumption, reflecting a vanishing hunter culture where elderly Inuit still adhere to the traditional hunters food with a high content of marine food, whereas the younger urbanized Inuit population consume food with a lower content of marine food and a higher content of terrestrial food. Danes consumed food of almost exclusively terrestrial origin. The present (13)C and (15)N analyses are in accordance with the dietary patterns obtained by dietary surveys.

Computational fluid dynamics modelling of hydraulics and sedimentation in process reactors during aeration tank settling.

Aeration tank settling is a control method allowing settling in the process tank during high hydraulic load. The control method is patented. Aeration tank settling has been applied in several waste water treatment plants using the present design of the process tanks. Some process tank designs have shown to be more effective than others. To improve the design of less effective plants, computational fluid dynamics (CFD) modelling of hydraulics and sedimentation has been applied. This paper discusses the results at one particular plant experiencing problems with partly short-circuiting of the inlet and outlet causing a disruption of the sludge blanket at the outlet and thereby reducing the retention of sludge in the process tank. The model has allowed us to establish a clear picture of the problems arising at the plant during aeration tank settling. Secondly, several process tank design changes have been suggested and tested by means of computational fluid dynamics modelling. The most promising design changes have been found and reported.

Intergeneric hybrids between Brassica napus and Orychophragmus violaceus containing traits of agronomic importance for oilseed rape breeding.

Protoplast fusions between Brassica napus and Orychophragmus violaceus for transfer of valuable traits to oilseed rape resulted in 257 somatic hybrid plants. Hybridity was confirmed by morphological, cytological and molecular means. Symmetric fusions gave rise to 131 plants. Fifty eight of these plants had an intermediate morphology and contained nuclear DNA corresponding to the sum of the parental species. All 131 plants were sterile with no pollen grains observed upon flowering. Another 126 plants were derived from asymmetric fusions in which protoplasts of the donor parent O. violaceus were irradiated by 100 or 200-Gy X-rays prior to fusion. Morphologically these plants showed a larger variation compared to the plants regenerated from symmetric fusion experiments. In contrast to plants obtained from symmetric fusions, fertile hybrids were recovered among regenerants from the asymmetric fusions. Twenty four of these plants released viable pollen grains and 14 of the determined 17 plants set seeds after either selfing or backcrossing to B. napus. Fourteen male-sterile plants were identified with female fertility. This observed male sterility most-likely originated from alloplasmic recombination and would be of great potential for the development of a new cytoplasmic male sterility system. The fatty acid composition of the fertile hybrids and their progenies showed a biased distribution towards the B. napus parent, which has a high erucic acid-content type. However, increased levels of palmitic and linoleic acids compared to B. napus were found in subsequent generations, as well as a reduced level of erucic acid.

Endothelium-dependent vasorelaxation in inhibited by in vivo depletion of vascular thiol levels: role of endothelial nitric oxide synthase.

Thiols like glutathione may serve as reducing cofactors in the production of nitric oxide (NO) and protect NO from inactivation by radical oxygen species. Depletion of thiol compounds reduces NO-mediated vascular effects in vitro and in vivo. The mechanisms underlying these actions are not clear, but may involve decreased synthesis of NO and/or increased degradation of NO. This study investigates the effect of glutathione depletion on the response to NO-mediated vasodilation induced by acetylcholine (Ach, 10 micrograms/kg), endothelial NO synthase (eNOS) activity and potential markers of vascular superoxide anion (O2.-) production in conscious chronically catheterized rats. Thiol depletion induced by buthionine sulfoximine (BSO, 1 g i.p. within 24 h) decreased the hypotensive effect of Ach by 30% (MAP reduction before BSO 27 +/- 3 mmHg, 19 +/- 3 mmHg after BSO, (mean +/- SEM), p < .05, n = 8). The impaired effect of Ach was associated with a significant reduction in eNOS activity (control: 7.7 +/- 0.8, BSO: 3.9 +/- 0.4 pmol/min/mg protein (p < .05), n = 6). In contrast, neither NADH/NADPH driven membrane-associated oxidases nor lucigenin reductase activity were significantly (p < .05) affected by BSO (BSO: 4415 +/- 123, control: 4105 +/- 455 counts/mg; n = 6) in rat aorta. It is concluded that in vivo thiol depletion results in endothelial dysfunction and a reduced receptor-mediated vascular relaxation. This effect is caused by reduced endothelial NO formation.

Pigs expressing salivary phytase produce low-phosphorus manure.

To address the problem of manure-based environmental pollution in the pork industry, we have developed the phytase transgenic pig. The saliva of these pigs contains the enzyme phytase, which allows the pigs to digest the phosphorus in phytate, the most abundant source of phosphorus in the pig diet. Without this enzyme, phytate phosphorus passes undigested into manure to become the single most important manure pollutant of pork production. We show here that salivary phytase provides essentially complete digestion of dietary phytate phosphorus, relieves the requirement for inorganic phosphate supplements, and reduces fecal phosphorus output by up to 75%. These pigs offer a unique biological approach to the management of phosphorus nutrition and environmental pollution in the pork industry.

Recessive resistance in Pisum sativum and potyvirus pathotype resolved in a gene-for-cistron correspondence between host and virus.

Pea seed-borne mosaic potyvirus (PSbMV) isolates are divided into pathotypes P-1, P-2, and P-4 according to their infection profile on a panel of Pisum sativum lines. P. sativum PI 269818 is resistant to P-1 and P-2 isolates and is susceptible to P-4 isolates. Resistance to P-1 is inherited as a single recessive gene, denoted sbm-1, and the pathogenicity determinant has previously been mapped to the virus-coded protein VPg. In the cultivar Bonneville, a second recessive gene, sbm-2, confers specific resistance to P-2. By exchanging cistrons between a P-2 and a P-4 isolate, the P3-6k1 cistron was identified as the PSbMV host-specific pathogenicity determinant on Bonneville. Exchange of P3-6k1 did not affect infection on PI 269818, and infection of Bonneville was not altered by substitution of the VPg cistron, indicating that P3-6k1 and VPg are independent determinants of pathotype-specific infectivity. On PI 269818 the pathogenicity determinant of both P-1 and P-2 mapped to the N terminus of VPg. This suggests that VPg from the P-1 and P-2 isolates are functionally similar on this host and that resistance to P-1 and P-2 in PI 269818 may operate by the same mechanism. Identification of VPg-sbm-1 and P3-6k1-sbm-2 as independent pairs of genetic interactors between PSbMV and P. sativum provides a simple explanation of the three known pathotypes of PSbMV. Furthermore, analysis of beta-glucuronidase-tagged P-2 virus indicated that sbm-2 resistance affected an early step in infection, implying that the P3-6k1 region plays a critical role in potyvirus replication or cell-to-cell movement.

Intramolecular glycosylation under neutral conditions for synthesis of 1,4-linked disaccharides.

[structure: see text]. A new method for intramolecular glycosylation, in which the donor and acceptor were linked via a 3,5-dinitrosalicylic acid derivative, was developed. Simply dissolving the tethered glycoside in CH3NO2 and warming to 40-60 degrees C led to formation of 1,4-linked disaccharides under neutral, hence, exceptionally mild, conditions.

Endothelial regulation of vasomotion in apoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin.

BACKGROUND: Altered endothelial cell nitric oxide (NO(*)) production in atherosclerosis may be due to a reduction of intracellular tetrahydrobiopterin, which is a critical cofactor for NO synthase (NOS). In addition, previous literature suggests that inactivation of NO(*) by increased vascular production superoxide (O(2)(*-)) also reduces NO(*) bioactivity in several disease states. We sought to determine whether these 2 seemingly disparate mechanisms were related. METHODS AND RESULTS: Endothelium-dependent vasodilation was abnormal in aortas of apoE-deficient (apoE(-/-)) mice, whereas vascular superoxide production (assessed by 5 micromol/L lucigenin) was markedly increased. Treatment with either liposome-entrapped superoxide dismutase or sepiapterin, a precursor to tetrahydrobiopterin, improved endothelium-dependent vasodilation in aortas from apoE(-/-) mice. Hydrogen peroxide had no effect on the decay of tetrahydrobiopterin, as monitored spectrophotometrically. In contrast, superoxide modestly and peroxynitrite strikingly increased the decay of tetrahydrobiopterin over 500 seconds. Luminol chemiluminescence, inhibitable by the peroxynitrite scavengers ebselen and uric acid, was markedly increased in apoE(-/-) aortic rings. In vessels from apoE(-/-) mice, uric acid improved endothelium-dependent relaxation while having no effect in vessels from control mice. Treatment of normal aortas with exogenous peroxynitrite dramatically increased vascular O(2)(*-) production, seemingly from eNOS, because this effect was absent in vessels lacking endothelium, was blocked by NOS inhibition, and did not occur in vessels from mice lacking eNOS. CONCLUSIONS: Reactive oxygen species may alter endothelium-dependent vascular relaxation not only by the interaction of O(2)(*-) with NO(*) but also through interactions between peroxynitrite and tetrahydrobiopterin. Peroxynitrite oxidation of tetrahydrobiopterin may represent a pathogenic cause of "uncoupling" of NO synthase.

Elements in autopsy liver tissue samples from Greenlandic Inuit and Danes. III. Zinc measured by X-ray fluorescence spectrometry.

The aim of the study was to measure the content of zinc (Zn) in liver tissue samples from Greenlandic Inuit using X-ray fluorescence spectrometry, and compare the results with those obtained in liver samples from Danes. Normal liver tissue samples was obtained at autopsy from 50 Greenlandic Inuit (27 men) with a median age of 61 years (range 23-83) and from 74 Danes (44 men) with a median age of 60 years (range 15-87). In the entire series, liver zinc content in Inuit was not significantly different compared with Danes. There was no significant gender difference in liver zinc content either in Inuit or in Danes. The content of zinc given as median (5-95 percentile) was in Inuit 3.809 mmol/kg dry liver (2.355-7.406), and in Danes 3.992 mmol/kg dry liver (2.499-8.645). There was a significant, positive correlation between liver zinc content and age in Danish women (r(s) = 0.43, p = 0.02), which could not be demonstrated in Danish men or in Inuit. Median hepatic zinc index (zinc content in mmol/kg dry weight divided by age in years) in Inuit was 0.073, and in Danes 0.080 (p = 0.3) without any significant difference between the two genders. In Inuit and Danes there was an inverse correlation between hepatic zinc index and age both in the two genders and in the entire series: Inuit: r(s) = -0.62, p < 0.0001; Danes: r(s) = -0.70, p < 0.0001. The results indicate that Inuit have liver zinc levels, which are similar to those found in Danes.

[Long-term results following cemented total hip alloplasty in primary hip arthrosis. What to expect?]. / Langtidsresultater efter cementeret total hoftealloplastik i behandlingen af primaer hofteartrose. Hvad må man forvente?

The aim was to investigate the age-, gender- and implant related survival up to 14 years postsurgery in patients with primary hiparthrosis in one or both hips and operated in county hospitals with cemented prosthesis designs. The subjects consisted of 1,199 patients operated in the years 1981-1990, and the cohort was followed till 31.12.1994. The 1,199 patients had a total of 1,477 cemented total hipalloplastics (THA's) inserted. Two hundred and fourty-eight patients died during follow-up. Until 1990, 278 patients had had both hips operated, and a further 58 patients had the contralateral hip operated during follow-up to 31.12.1994. Fourty-nine hips were revised between four and 14 years (median: nine years) postsurgery. The cumulative survival for all THA's was 92.5%. Respective figures for the Richard Series 2 and the Charnley-prosthesis were 91.5% and 92%, now more than 14 years from the first operations. In conclusion, cemented total hip arthroplasty is a good treatment option for patients with primary hip arthrosis. Younger patients have an increased risk of revision, and alternative fixation may be considered. With an overall prosthesis-survival more than 14 years postsurgery of 92.5%, the treatment can take place at local orthopaedic departments. Our results are comparable to figures from the Swedish national register.