Klinik und Poliklinik für Orthopädie, Physikalische Medizin und Rehabilitation

BACKGROUND: Intermittent hemodialysis is widely used as renal-replacement therapy in patients with acute renal failure, but an adequate dose has not been defined. We performed a prospective study to determine the effect of daily intermittent hemodialysis, as compared with conventional (alternate-day) intermittent hemodialysis, on survival among patients with acute renal failure. METHODS: A total of 160 patients with acute renal failure were assigned to receive daily or conventional intermittent hemodialysis. Survival was the primary end point of the study. The duration of acute renal failure and the frequency of therapy-related complications were secondary end points. RESULTS: The two study groups were similar with respect to age, sex, cause and severity of acute renal failure, medical or surgical intensive care setting, and the score on the Acute Physiology, Age, and Chronic Health Evaluation. Daily hemodialysis resulted in better control of uremia, fewer hypotensive episodes during hemodialysis, and more rapid resolution of acute renal failure (mean [+/-SD], 9+/-2 vs. 16+/-6 days; P=0.001) than did conventional hemodialysis. The mortality rate, according to the intention-to-treat analysis, was 28 percent for daily dialysis and 46 percent for alternate-day dialysis (P=0.01). In a multiple regression analysis, less frequent hemodialysis (on alternate days, as opposed to daily) was an independent risk factor for death. CONCLUSIONS: The high mortality rate among critically ill patients with acute renal failure who require renal-replacement therapy is related to both coexisting conditions and uremic damage to other organ systems. Intensive hemodialysis reduces mortality without increasing hemodynamically induced morbidity.

Microsomes from rat liver form hydrogen peroxide in the presence of an NADPH‐generating system in proportion to protein concentrations as determined by three independent methods: ferrithiocyanate, cytochrome c peroxidase, and scopoletin fluorescence. Maximal rates observed were about 15 μmol H 2 O 2 /g microsomal protein per minute. The oxygen concentration for half‐maximal rates was 50 μM. It is suggested that NADPH‐dependent hydrogen peroxide formation in microsomes is mainly due to NADPH oxidase; however, partial inhibition by carbon monoxide suggests that about one third arises from the autoxidation of cytochrome P‐450. Similarities exist between microsomal acetaldehyde production from ethanol ( i.e. the microsomal ethanol‐oxidizing system of Lieber and DeCarli [4]) and hydrogen peroxide formation: viz. requirement for NADPH and oxygen, identical oxygen concentrations for halfmaximal rates, and sensitivity to carbon monoxide. Microsomal acetaldehyde production in the presence of either an NADPH‐ or an H 2 O 2 ‐generating system exhibits identical characteristics as follows: (a) ethanol concentration for half‐maximal rates ( i.e. 12 mM); (b) dependency of maximal rates on rates of hydrogen peroxide formation; (c) competitive inhibition by peroxidatic substrates for catalase, e.g. formate (half‐maximal effect: 150 μM); (d) inhibition by catalase inhibitors, e.g. azide (half‐maximal effect: 50 μM), with identical azide insensitive rates; (e) diminished acetaldehyde production in microsomes from rats pretreated with aminotriazole or pyrazole with identical residual rates. Moreover, NADPH‐dependent acetaldehyde production is suppressed in the presence of an active H 2 O 2 ‐utilizing system. Thus, it is concluded that the NADPH‐dependent microsomal ethanol‐oxidizing system of Lieber and DeCarli [4] is due to a hydrogen peroxide formation from NADPH and a subsequent peroxidation of ethanol by contaminating catalase. The data indicate that the existence of a unique system in addition to the peroxidatic reaction of catalase as postulated recently [4] is highly doubtful.

HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. HDL binding to scavenger receptor-BI has been shown to activate eNOS, although the responsible HDL entities and signaling pathways have remained enigmatic. Here we show that HDL stimulates NO release in human endothelial cells and induces vasodilation in isolated aortae via intracellular Ca 2+ mobilization and Akt-mediated eNOS phosphorylation. The vasoactive effects of HDL could be mimicked by three lysophospholipids present in HDL: sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and lysosulfatide (LSF). All three elevated intracellular Ca 2+ concentration and activated Akt and eNOS, which resulted in NO release and vasodilation. Deficiency of the lysophospholipid receptor S1P 3 (also known as LPB 3 and EDG3) abolished the vasodilatory effects of SPC, S1P, and LSF and reduced the effect of HDL by approximately 60%. In endothelial cells from S1P 3 -deficient mice, Akt phosphorylation and Ca 2+ increase in response to HDL and lysophospholipids were severely reduced. In vivo, intra-arterial administration of HDL or lysophospholipids lowered mean arterial blood pressure in rats. In conclusion, we identify HDL as a carrier of bioactive lysophospholipids that regulate vascular tone via S1P 3mediated NO release. This mechanism may contribute to the vasoactive effect of HDL and represent a novel aspect of its antiatherogenic function.

About 5 years ago a Battelle Colloquium on "The Physical Basis of Heterogeneous Catalysis" was held in honor of Professor Emmett where he presented an introductory talk on ″Fifty Years of Progress in the Study of the Catalytic Synthesis of Ammonia″ [1], a field to which he had made significant contributions during this whole period. So why another report on this topic? Justification can perhaps partly be obtained by some of Professor Emmett's concluding remarks which were not completely decisive with respect to the mechanism of this reaction: 'The experimental work of the past 50 years leads to the conclusion that the rate-determining step in ammonia synthesis over iron catalysts is the chemisorption of nitrogen. The question as to whether the nitrogen species involved on the surface is molecular or atomic is still not conclusively resolved. In fact, our own work in this field was mainly induced by this paper, and continuing discussions and correspondence with Professor Emmett were extremely helpful during its progress. I am therefore very much honored to be this year's recipient of the Emmett Award.

BACKGROUND: The integrin alphavbeta3 plays an important role in angiogenesis and tumor cell metastasis, and is currently being evaluated as a target for new therapeutic approaches. Several techniques are being studied to enable noninvasive determination of alphavbeta3 expression. We developed [(18)F]Galacto-RGD, a (18)F-labeled glycosylated alphavbeta3 antagonist, allowing monitoring of alphavbeta3 expression with positron emission tomography (PET). METHODS AND FINDINGS: Here we show by quantitative analysis of images resulting from a small-animal PET scanner that uptake of [(18)F]Galacto-RGD in the tumor correlates with alphavbeta3 expression subsequently determined by Western blot analyses. Moreover, using the A431 human squamous cell carcinoma model we demonstrate that this approach is sensitive enough to visualize alphavbeta3 expression resulting exclusively from the tumor vasculature. Most important, this study shows, that [(18)F]Galacto-RGD with PET enables noninvasive quantitative assessment of the alphavbeta3 expression pattern on tumor and endothelial cells in patients with malignant tumors. CONCLUSIONS: Molecular imaging with [(18)F]Galacto-RGD and PET can provide important information for planning and monitoring anti-angiogenic therapies targeting the alphavbeta3 integrins and can reveal the involvement and role of this integrin in metastatic and angiogenic processes in various diseases.

The proinflammatory cytokine IL-17A is considered a crucial player in rheumatoid arthritis (RA) pathogenesis. In experimental models of autoimmune arthritis, it has been suggested that the cellular source of IL-17A is CD4(+) T cells (Th17 cells). However, little is known about the source of IL-17 in human inflamed RA tissue. We explored the cellular sources of IL-17A in human RA synovium. Surprisingly, only a small proportion of IL-17-expressing cells were T cells, and these were CCR6 negative. Unexpectedly, the majority of IL-17A expression colocalized within mast cells. Furthermore, we demonstrated in vitro that mast cells produced RORC-dependent IL-17A upon stimulation with TNF-alpha, IgG complexes, C5a, and LPS. These data are consistent with a crucial role for IL-17A in RA pathogenesis but suggest that in addition to T cells innate immune pathways particularly mediated via mast cells may be an important component of the effector IL-17A response.

IMPORTANCE: Patients with soft tissue sarcoma are at risk for local recurrence and distant metastases despite optimal local treatment. Preoperative anthracycline plus ifosfamide chemotherapy improves outcome in common histological subtypes. OBJECTIVE: To analyze whether the previously reported improvement in local progression-free survival by adding regional hyperthermia to neoadjuvant chemotherapy translates into improved survival. DESIGN, SETTING, AND PARTICIPANTS: Open-label, phase 3 randomized clinical trial to evaluate the efficacy and toxic effects of neoadjuvant chemotherapy plus regional hyperthermia. Adult patients (age ≥18 years) with localized soft tissue sarcoma (tumor ≥5 cm, French Federation Nationale des Centers de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep) were accrued across 9 centers (6, Germany; 1, Norway; 1, Austria; 1, United States) from July 1997 to November 2006. Follow-up ended December 2014. INTERVENTIONS: After stratification for tumor presentation and site, patients were randomly assigned to either neoadjuvant chemotherapy consisting of doxorubicin, ifosfamide, and etoposide alone, or combined with regional hyperthermia. MAIN OUTCOMES AND MEASURES: The primary end point was local progression-free survival. Secondary end points included treatment safety and survival, with survival defined from date of randomization to death due to disease or treatment. Patients lost to follow-up were censored at the date of their last follow-up. RESULTS: A total of 341 patients were randomized, and 329 (median [range] age, 51 [18-70] years; 147 women, 182 men) were eligible for the intention-to-treat analysis. By December 2014, 220 patients (67%; 95% CI, 62%-72%) had experienced disease relapse, and 188 (57%; 95% CI, 52%-62%) had died. Median follow-up was 11.3 years. Compared with neoadjuvant chemotherapy alone, adding regional hyperthermia improved local progression-free survival (hazard ratio [HR], 0.65; 95% CI, 0.49-0.86; P = .002). Patients randomized to chemotherapy plus hyperthermia had prolonged survival rates compared with those randomized to neoadjuvant chemotherapy alone (HR, 0.73; 95% CI, 0.54-0.98; P = .04) with 5-year survival of 62.7% (95% CI, 55.2%-70.1%) vs 51.3% (95% CI, 43.7%-59.0%), respectively, and 10-year survival of 52.6% (95% CI, 44.7%-60.6%) vs 42.7% (95% CI, 35.0%-50.4%). CONCLUSIONS AND RELEVANCE: Among patients with localized high-risk soft tissue sarcoma the addition of regional hyperthermia to neoadjuvant chemotherapy resulted in increased survival, as well as local progression-free survival. For patients who are candidates for neoadjuvant treatment, adding regional hyperthermia may be warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00003052.

BACKGROUND: Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared. METHODS: In a double-blinded crossover trial, we compared the uptake of three EPA+DHA formulations derived from fish oil (re-esterified triacylglycerides [rTAG], ethyl-esters [EE]) and krill oil (mainly PL). Changes of the FA compositions in plasma PL were used as a proxy for bioavailability. Twelve healthy young men (mean age 31 y) were randomized to 1680 mg EPA+DHA given either as rTAG, EE or krill oil. FA levels in plasma PL were analyzed pre-dose and 2, 4, 6, 8, 24, 48, and 72 h after capsule ingestion. Additionally, the proportion of free EPA and DHA in the applied supplements was analyzed. RESULTS: The highest incorporation of EPA+DHA into plasma PL was provoked by krill oil (mean AUC0-72 h: 80.03 ± 34.71%*h), followed by fish oil rTAG (mean AUC0-72 h: 59.78 ± 36.75%*h) and EE (mean AUC0-72 h: 47.53 ± 38.42%*h). Due to high standard deviation values, there were no significant differences for DHA and the sum of EPA+DHA levels between the three treatments. However, a trend (p = 0.057) was observed for the differences in EPA bioavailability. Statistical pair-wise group comparison's revealed a trend (p = 0.086) between rTAG and krill oil. FA analysis of the supplements showed that the krill oil sample contained 22% of the total EPA amount as free EPA and 21% of the total DHA amount as free DHA, while the two fish oil samples did not contain any free FA. CONCLUSION: Further studies with a larger sample size carried out over a longer period are needed to substantiate our findings and to determine differences in EPA+DHA bioavailability between three common chemical forms of LC n-3 FA (rTAG, EE and krill oil). The unexpected high content of free EPA and DHA in krill oil, which might have a significant influence on the availability of EPA+DHA from krill oil, should be investigated in more depth and taken into consideration in future trials.

GSH is the major antioxidant and detoxifier of xenobiotics in mammalian cells. A strong decrease of intracellular GSH has been frequently linked to pathological conditions like ischemia/reperfusion injury and degenerative diseases including diabetes, atherosclerosis, and neurodegeneration. Although GSH is essential for survival, the deleterious effects of GSH deficiency can often be compensated by thiol-containing antioxidants. Using three genetically defined cellular systems, we show here that forced expression of xCT, the substrate-specific subunit of the cystine/glutamate antiporter, in gamma-glutamylcysteine synthetase knock-out cells rescues GSH deficiency by increasing cellular cystine uptake, leading to augmented intracellular and surprisingly high extracellular cysteine levels. Moreover, we provide evidence that under GSH deprivation, the cytosolic thioredoxin/thioredoxin reductase system plays an essential role for the cells to deal with the excess amount of intracellular cystine. Our studies provide first evidence that GSH deficiency can be rescued by an intrinsic genetic mechanism to be considered when designing therapeutic rationales targeting specific redox enzymes to combat diseases linked to GSH deprivation.

BACKGROUND: Mechanical properties and biocompatibility make zirconia ceramics suitable implant material. The characteristics of tooth-color like, the ability to be machined and the low plaque affinity make zirconia especially suitable as a dental implant material. The influence of surface modification on the osseointegration of this material has not been extensively investigated. PURPOSE: Long-term investigations with titanium implants have shown superior biomechanical results with the sandblasted acid-etched (SLA) surface, demonstrating a high bone-implant interaction. The objective of this study was to compare two different zirconia surface topographies biomechanically and histologically with the well-documented titanium SLA surface. MATERIAL AND METHODS: Zirconia implants with either a machined (ZrO2m) or a sandblasted (rough, ZrO2r) surface were manufactured with the exact same cylindrical shape with a standard ITI thread configuration as the SLA titanium implants. The incisors 2 and 3 were removed from both sides of the maxillae of 13 adult miniature pigs and the tissues left to heal for 6 months. After this time period the animals received a total of 78 implants using a randomized scheme, with the titanium SLA implant used as an only individual reference. After healing periods of 4, 8, and 12 weeks 20, 24, and 25 implants, respectively, were subjected to removal torque tests (RTQ) as the main biomechanical analysis of the of the study. A fewer number was resected on bloc, embedded in methylmethacrylat and analyzed for their direct bone apposition under a light microscope. RESULTS: Surface analysis revealed the highest surface roughness for the SLA-implant, followed by ZrO2r and ZrO2m. The turned ZrO2m implants showed statistically significant lower RTQ values than the other two implants types after 8 and 12 weeks, while the SLA implant showed significantly higher RTQs values than ZrO2r surface after 8 weeks. Differences in the bone apposition were observed in the histomorphometric analysis using light microscopy for all surfaces at any time point. CONCLUSION: The findings suggest that ZrO2r implants can achieve a higher stability in bone than ZrO2m implants. Roughening the turned zirconia implants enhances bone apposition and has a beneficial effect on the interfacial shear strength.

In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study. Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (P value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03-1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04-12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07-6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17-0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls; P<0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls.

The endoplasmic reticulum (ER) is an important site for protein folding and becomes "stressed" when its capacity to fold proteins is overwhelmed. In response, "unfolded protein response" (UPR) genes are induced, increasing the capacity to fold proteins; if the response is insufficient, then apoptosis ensues. For investigation of whether proteinuria and hyperglycemia induce ER stress in renal epithelial cells, microarray data from biopsies of established diabetic nephropathy (DN) were analyzed. Expression of UPR genes was significantly different in these biopsies than in control kidneys or biopsies of patients with mild DN, suggesting an association between the degree of DN and UPR gene expression. Expression of the transcription factor XBP1 and the ER chaperones HSPA5 and HYOU1 were increased, but the proapoptotic gene DDIT3 was unchanged. These findings were replicated in an independent cohort of patients with established DN by real-time reverse transcriptase-PCR. Immunofluorescence of renal biopsies from patients with DN confirmed the upregulation for HSPA5 and HYOU1 proteins in tubular epithelia. In biopsies of minimal-change disease, the mRNA levels of some ER stress molecules were also induced, but protein expression of HSPA5 and HYOU1 remained significantly lower than that observed in DN. Exposure of renal tubular epithelial cells to albumin and high glucose in vitro enhanced expression of genes involved in ER stress. These observations suggest that in proteinuric diseases, tubular epithelial cells undergo ER stress, which induces an adaptive, protective UPR. Although this may protect the cells from ER stress, persistence of hyperglycemia and proteinuria may eventually lead to apoptosis.

OBJECTIVE: To examine the in vivo accuracy and precision of magnetic resonance imaging (MRI)-based assessment of cartilage loss in patients with severe osteoarthritis (OA) of the knee. METHODS: High-resolution MRI images of the tibial cartilage were obtained in 8 patients prior to total knee arthroplasty, using a water-excitation gradient-echo MRI sequence (acquisition time 6 minutes 19 seconds; spatial resolution 1.2 x 0.31 x 0.31 mm3). The MRI measurements were repeated after joint repositioning. The precision of the cartilage volume and thickness computations was determined after 3-dimensional reconstruction. During surgery, the tibial plateaus were resected, and the MRI data were compared with water displacement of surgically retrieved cartilage. RESULTS: The standard deviation (coefficient of variation) of repeated tibial cartilage volume measurements was 56 mm3 (5.5%) medially and 59 mm3 (3.8%) laterally. The deviation from surgically removed tissue was -13%, on average, with a high linear correlation between both methods (r = 0.98). In patients with varus OA, the tissue loss was estimated to be 1,290 mm3 in the medial tibia and 1,150 mm3 in the lateral tibia, compared with the data in healthy volunteers. CONCLUSION: Noninvasive quantitative MRI-based analysis of cartilage morphometry in severe OA is accurate, precise, and displays high potential diagnostic value.

Ninety percent of patients with minor head injury (MHI) who have cranial computed tomography (CCT) under the present clinical decision rules have normal scans. Serum concentrations of the astroglial protein S-100B were recently found to provide useful information, but these studies were too small to provide a statistically safe basis for changing the present rule. We have investigated whether S-100B concentrations in patients with MHI can provide additional information to improve indication of the need for an initial CCT scan. One thousand three hundred nine patients with MHI were enrolled in this prospective, multicenter study. All had a CCT scan to confirm diagnosis in accordance with the present clinical decision rules. S-100B was measured in serum samples obtained upon admission. Data were analyzed using contingency table and receiver operating characteristic curve and compared with those for healthy donors (n = 540) and with those for patients with moderate to severe head injury (n = 55). Of the 1309 patients studied, 93 exhibited trauma-relevant intracerebral lesions on the CCT scan (CCT+). With a cutoff limit of 0.10-microg/L S-100B (95th percentile of values in healthy volunteers), CCT+ patients were identified with a sensitivity level of 99% (95% confidence interval, 96% - 100%) and a specificity level of 30% (95% confidence interval, 29% - 31%). Adding the measurement of S-100B concentration to the clinical decision rules for a CCT scan in patients with MHI could allow a 30% reduction in scans. A prospective study of the clinical value of S-100B measurement in such patients is now under way.

The role of transforming growth factor beta 2 (TGF-beta 2) in the pathogenesis of systemic sclerosis (SSc) was investigated by in situ hybridization of skin biopsies from six patients with SSc. Two patients with acute systemic lupus erythematosis (SLE), one with acute dermatomyositis (DM), and three healthy individuals were used as controls. TGF-beta 2 mRNA was found to be co-localized with pro alpha 1(I) collagen expression around dermal blood vessels in all patients with the inflammatory stage of SSc, whereas there was no expression of either gene in the dermis of patients in the fibrotic stage, the SLE patients or the normal controls. These findings provide evidence that TGF-beta 2 released by inflammatory cells around blood vessels may play a role in mediating the collagen gene disregulation in fibrosis.

OBJECTIVES: Biomaterial-associated bacterial infections present common and challenging complications with medical implants. The purpose of this study was to determine the antibacterial properties of a low molecular weight biodegradable poly(D,L-lactic acid) coating with integrated antibiotics gentamicin and teicoplanin. METHODS: Coating of Kirschner-wires was carried out by a solvent casting technique under aseptic conditions with and without incorporated antibiotics. Release kinetics of gentamicin and teicoplanin were studied in phosphate-buffered saline. Initial bacterial adhesion of Staphylococcus epidermidis on coated and bare implants was determined by radiolabelling and counts of detached viable organisms. RESULTS: The incorporated antibiotics showed a continuous release over a period of at least 96 h with an initial peak of release in the first 6 h. Attachment of non-viable microorganisms, detected by radiolabelled bacteria, was increased significantly by the polymer coatings (P < 0.05). In contrast, the number of viable bacteria was reduced by the pure polymer (P < 0.01) and further by the polymer-antibiotic combinations (P < 0.05). CONCLUSIONS: Poly(D,L-lactic acid) coating of implants could offer new perspectives in preventing biomaterial-associated infections. Combinations with other drugs to formulate custom-tailored implant surfaces are feasible.

PURPOSE OF REVIEW: In the last 2 years in the cardiovascular field eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been investigated in terms of their epidemiology and vascular biology, and in large-scale intervention trials, and incorporated into the guidelines of cardiac societies. EPA and DHA have advanced from scientific research into everyday practice, a development reviewed here. RECENT FINDINGS: EPA and DHA are antiarrhythmic on the supraventricular and ventricular levels, besides having an anti-atherosclerotic effect. Fish rich in EPA and DHA, contaminated with methyl-mercury, appears less protective. Large-scale clinical trials demonstrated that morbidity can be reduced with EPA even in a population already consuming large amounts of EPA and DHA. Therapy with EPA and DHA can be monitored with the omega-3 index, a risk factor for sudden cardiac death. EPA and DHA appear to be cost-saving in the USA, and, as Omacor, are cost-effective in several European countries. SUMMARY: European and American Cardiac Societies incorporated EPA and DHA into recent treatment guidelines for myocardial infarction, prevention of cardiovascular disease, treatment of ventricular arrhythmias and prevention of sudden cardiac death. Physicians need to reduce the burden of cardiovascular disease by advocating EPA and DHA to all patients likely to benefit.

BACKGROUND: We examined the association between vitamin D [25(OH)D] level and disease progression in HIV infection. METHODS: Within the EuroSIDA study, 2000 persons were randomly selected for 25(OH)D measurement in stored plasma samples closest to study entry. 25(OH)D results were stratified into tertiles. Factors associated with 25(OH)D levels and associations of 25(OH) levels with subsequent risk of all-cause mortality, AIDS and non-AIDS events were analyzed. RESULTS: Of 1985 persons with 25(OH)D levels available, 23.7% had 25(OH)D below 10, 65.3% between 10 and 30, and 11% above 30 ng/ml. At the time of 25(OH)D measurement, older persons, persons of black ethnic origin, living outside Southern Europe/Argentina, sampled during winter, and infected with HIV through nonhomosexual exposure were at higher odds of having low 25(OH)D levels, whereas persons receiving protease inhibitors were at lower odds. Compared to those in the lowest 25(OH)D tertile (<12 ng/ml), those in the middle (12-20) and higher (>20) tertiles had a significantly lower risk of clinical progression during subsequent follow-up. Adjusted incidence rate ratios for all-cause mortality were 0.68 (95% CI 0.47-0.99, P = 0.045) and 0.56 (95% CI 0.37-0.83, P = 0.0039), and for AIDS events were 0.58 (95% CI 0.39-0.87, P = 0.0086) and 0.61 (95% CI 0.40-0.93, P = 0.020), for the middle and higher tertiles, respectively. There was a similar, nonsignificant reduced incidence of non-AIDS events in the middle and higher tertiles. CONCLUSION: 25(OH)D deficiency was frequent in HIV-infected persons (83% on combined antiretroviral therapy), and was independently associated with a higher risk of mortality and AIDS events. Causality relationships should be examined, because of potential public health consequences.

The standard redox potential of ubiquinone in submitochondrial particles is measured by equilibration with the succinate/fumarate system to about 65 mV at pH 7, with the redox ratio, n = 2. The pH dependence is ‐60 mV/Δ pH. The lower value measured for bound ubiquinone is discussed in comparison with the value found for isolated ubiquinone (104 to 112 mV, pH 7) determined in ethanol‐HCl. In parallel experiments the standard redox potential of cytochrome b was measured to 72.5mV at pH 7. The pH dependence is Δ E/Δ pH = 0 at pH &lt; 6.8 and ‐ 60 mV ΔHp at pH &gt; 6.8.

BACKGROUND: There is a debate currently about whether different chemical forms of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are absorbed in an identical way. The objective of this study was to investigate the response of the omega-3 index, the percentage of EPA+DHA in red blood cell membranes, to supplementation with two different omega-3 fatty acid (n-3 FA) formulations in humans. DESIGN: The study was conducted as a double-blinded placebo-controlled trial. A total of 150 volunteers was randomly assigned to one of the three groups: (1) fish oil concentrate with EPA+DHA (1.01 g+0.67 g) given as reesterified triacylglycerides (rTAG group); (2) corn oil (placebo group) or (3) fish oil concentrate with EPA+DHA (1.01 g+0.67 g) given as ethyl ester (EE group). Volunteers consumed four gelatine-coated soft capsules daily over a period of six months. The omega-3 index was determined at baseline (t(0)) after three months (t(3)) and at the end of the intervention period (t(6)). RESULTS: The omega-3 index increased significantly in both groups treated with n-3 FAs from baseline to t(3) and t(6) (P<0.001). The omega-3 index increased to a greater extent in the rTAG group than in the EE group (t(3): 186 versus 161% (P<0.001); t(6): 197 versus 171% (P<0.01)). CONCLUSION: A six-month supplementation of identical doses of EPA+DHA led to a faster and higher increase in the omega-3 index when consumed as triacylglycerides than when consumed as ethyl esters.