Structural activity relationship analysis (SAR) and in vitro testing reveal the anti-ageing potential activity of acetyl aspartic acid.

BACKGROUND: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap), aiming for identification of new compounds with anti-ageing properties. OBJECTIVE: The aim of this study was to use structural activity relationship (SAR) analysis to identify a predictive mechanism of action of A-A-A. The findings from SAR will be further characterized by in vitro activity testing. Furthermore, we aimed to investigate the role of polymerized filamentous F-actin in ageing fibroblasts and to evaluate the effect of A-A-A on this model. METHODS: To predict the mode of action of A-A-A, we used the PASS computer program as a SAR model. In vitro, scratch motility tests with immortalized keratinocytes were used as a model for wound healing potential. Matrix metalloproteinase 1-3 (MMP 1-3) was analysed using multiplex protein assays (Luminex), and polymerized actin was detected by phalloidin staining in dermal fibroblasts (HDF). RESULTS: SAR analysis predicted that A-A-A would possess both epidermal and dermal activities with identification of wound healing and MMP inhibition potential. Further in vitro studies confirmed the wound healing potential using keratinocyte scratch motility assays. We were also able to confirm the dermal activities predicted by inhibition of MMP (MMP 1-3) in HDF by A-A-A. In addition, we found a positive relationship between age and F-actin expression. We also discovered that stimulation of HDF with A-A-A for 72 h significantly reduced the polymerized cytoskeletal network as visualized by inhibition of F-actin expression. In fact, A-A-A leveraged the expression of F-actin in middle-aged female fibroblasts (50 years of age) to the level of young female fibroblasts (30 years of age), corresponding to a 40% reduction in F-actin expression. CONCLUSION: Using an in silico and in vitro approach, we were able to demonstrate that A-A-A has the capacity to target different compartments of the skin through keratinocyte regeneration, MMP inhibition and relief in fibroblasts stiffness by reduction of F-actin cytoskeletal network in HDF.

In vivo topical application of acetyl aspartic acid increases fibrillin-1 and collagen IV deposition leading to a significant improvement of skin firmness.

OBJECTIVE: Acetyl aspartic acid (A-A-A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A-A-A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% A-A-A was well tolerated. In this study, the aim was to investigate whether A-A-A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. METHOD: Two separate double-blind vehicle-controlled in vivo studies were conducted using a 1% A-A-A containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of A-A-A on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to A-A-A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. RESULTS: Twelve-day topical application of 1% A-A-A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A-A-A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A-A-A. However, only A-A-A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A-A-A as a skin-firming active ingredient. CONCLUSION: In this study, we showed the in vivo efficacy of 1% A-A-A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti-ageing 'cosmeceutical' ingredient answering the needs of our key consumer base.

The use of gene arrays and corresponding connectivity mapping (Cmap) to identify novel anti-ageing ingredients.

OBJECTIVE: The need for effective 'anti-ageing' treatments, in particular for the management of photodamaged skin, prompted us to develop a novel method to identify new active ingredients. The model utilized a gene profiling study with corresponding connectivity mapping (Cmap) to identify novel anti-ageing compounds using all-trans retinoic acid (RA) as the lead compound due to its beneficial effect on photodamaged skin and skin firmness. METHOD: A vehicle-controlled clinical study including nine healthy Caucasian female volunteers aged 57 ± 7 (mean ± SEM) exhibiting photodamage on their lower outer forearms was conducted. The volunteers applied RA once daily on photodamaged skin for 7 days, and biopsies were subjected to Affymetrix gene arrays. Connectivity mapping (Cmap), examining hundreds of gene expression profiles, was run on the gene signature of RA-treated photodamaged skin to identify small bioactive compounds. RESULTS: Affymetrix gene array identified 19 genes significantly differentially expressed after application of RA. Corresponding Cmap analysis revealed six natural bioactive compounds including N-acetyl aspartic acid (A-A-A) showing similar activity to RA on the differentially expressed genes identified. CONCLUSION: Based on RA mimicking gene array activity, potential use within skincare on molecular size, safety assessment and sourcing, we identified the natural amino acid, A-A-A as a potential candidate to treat ageing skin.

Phakic intraocular lens explantation: causes in 240 cases.

PURPOSE: To describe the main causes of explantation of phakic intraocular lenses (PIOLs) according to the anatomical site of implantation (angle supported, iris fixated, or posterior chamber). METHODS: This multicentric, retrospective, and consecutive study sponsored by the Spanish Ministry of Health comprised a total of 240 eyes (226 patients) explanted due to PIOL complications. Clinical data of 144 angle-supported lenses, 24 iris-fixated lenses, and 72 posterior chamber lenses explanted were recorded preoperatively and postoperatively. RESULTS: Mean age of the patients at explantation was 46.30 ± 11.84 years (range: 25 to 80 years). The mean time between implantation and explantation was 381.14 ± 293.55 weeks (range: 0.00 to 1,551.17 weeks). It was 422.33 ± 287.81 weeks for the angle-supported group, 488.03 ± 351.95 weeks for the iris-fixated group, and 234.11 ± 4,221.60 weeks for the posterior chamber group. It was 8.10 ± 5.52 years for the angle-supported group, 9.36 ± 6.75 years for the iris-fixated group, and 4.49 ± 4.25 years for the posterior chamber group. This period of time was significantly shorter in the posterior chamber group (P < .001). Overall, the main causes of explantation were cataract formation (132 eyes, 55%), endothelial cell loss (26 eyes, 10.83%), corneal decompensation (22 eyes, 9.17%), PIOL dislocation/decentration (16 eyes, 6.67%), inadequate PIOL size or power (12 eyes, 5%), and pupil ovalization (10 cases, 4.17%). Cataract development was the cause of explantation in 51.39% of angle-supported cases, 45.83% of iris-fixated cases, and 65.28% of posterior chamber cases. Endothelial cell loss was the cause of explantation in 15.97% of angle-supported PIOLs, 8.33% of iris-fixated PIOLs, and 1.39% of posterior chamber PIOLs. CONCLUSIONS: Cataract is the main cause of PIOL explantation, especially in posterior chamber PIOLs. In the angle-supported group, endothelial cell loss was the second cause of explantation.

The impact of antihyperlipidemic drugs on the viral load of patients with chronic hepatitis C infection: a meta-analysis.

Several studies investigating the role of statins and fibrates in chronic hepatitis C virus (HCV) infection offered so far conflicting evidence regarding the antiviral potency of these medications, whereas combination of these drugs with pegylated interferon and ribavirin improved in some trials therapeutic outcome. We conducted a literature search to identify trials that included monoinfected HCV patients, treated with statins or fibrates as monotherapy with the primary end point of our meta-analysis being the quantitative change of HCV-RNA induced by these medications. Logarithmic changes of the viral load (ΔlogVL) and confidence intervals (CIs) were calculated according to the DerSimonian-Laird estimate. Statistical heterogeneity was assessed with the I² statistic. We identified eight observational studies that evaluated the potency of bezafibrate and different statins as monotherapy to induce a significant reduction of HCV-RNA in HCV-monoinfected patients (n = 281). Overall, a significant reduction of viral load with mean 0.19 [log10 IU/mL] (95%-confidence interval, (CI) 0.11-0.28) could be observed when antihyperlipidemic medications were administered. Bezafibrate featured the highest antiviral efficacy (0.45 log10 reduction, 95%-CI, 0.17-0.72) among all medications and fluvastatin (0.20 log10 reduction, 95%-CI, 0.09-0.31) among all statins tested. Based on meta-analysis, fibrates and statins induce a reduction of HCV viral load. We suggest that the addition of statins and fibrates to antiviral regimes, especially in HCV patients with concomitant dyslipidemia, could beside the established reduction of cardiovascular risk increase the potency of antiviral therapy.

Transcriptional changes in organoculture of full-thickness human skin following topical application of all-trans retinoic acid.

In this study, we developed an organoculture of human skin to investigate the effect of topical applied all-trans retinoic acid using a gene array approach. We could by using this approach confirm previous studies on genes activated by RA in keratinocyte monocultures and also provide new insights on genes that are relevant to RA-activation in human skin. The results in the present study show this model represent a valuable pre-clinical model for studying the effects of retinoids in skin.

Structure-function relationships in hardwood--insight from micromechanical modelling.

A micromechanical model is presented that predicts the stiffness of wood tissues in their three principal anatomical directions, across various hardwood species. The wood polymers cellulose, hemicellulose, and lignin, common to all wood tissues, serve as the starting point. In seven homogenisation steps, the stiffnesses of these polymers are linked to the macroscopic stiffness. The good agreement of model predictions and corresponding experimental data for ten different European and tropical species confirms the functionality and accuracy of the model. The model enables investigating the influence of individual microstructural features on the overall stiffness. This is exploited to elucidate the mechanical effects of vessels and ray cells. Vessels are shown to reduce the stiffness of wood at constant overall density. This supports that a trade-off exists between the hydraulic efficiency and the mechanical support in relation to the anatomical design of wood. Ray cells are shown to act as reinforcing elements in the radial direction.

A randomized controlled trial adding fluvastatin to peginterferon and ribavirin for naïve genotype 1 hepatitis C patients.

Fluvastatin or simvastatin has demonstrable antiviral activity against hepatitis C virus (HCV) as monotherapy. The safety and efficacy of adding fluvastatin or simvastatin to peginterferon/ribavirin for 48 weeks was tested in HCV genotype 1 naïve-to-treatment veterans. Thirty-seven naïve-to-treatment genotype 1 HCV patients were randomized to either a control group (n = 20) to receive peginterferon alfa plus ribavirin or an experimental group (n = 18) to similarly receive peginterferon alfa plus ribavirin as well as fluvastatin 20 mg/day. In addition, seven patients who presented for HCV treatment already were on simvastatin and could not be withdrawn. These simvastatin users were not randomized but were entered into a concurrent prospective pilot arm. There were no unique safety issues with fluvastatin or simvastatin when these drugs were given with peginterferon/ribavirin for 48 weeks. Thirteen of 25 statin patients achieved sustained viral response (SVR), while 5 of 20 control patients achieved SVR. Analysis of SVR by intention-to-treat showed P = 0.078. In this phase 2 study, there were no safety issues with the addition of fluvastatin or simvastatin to peginterferon and ribavirin for 48 weeks. There was a trend towards improvement in SVR when fluvastatin or simvastatin was administered with peginterferon/ribavirin. The size of the groups did not reach the prestudy size thought needed to show significant difference (type II error). These results support the significant results of two other larger randomized controlled trials reported using the same dose of fluvastatin in naïve-to-treatment genotype 1 HCV patients.

Femtosecond-assisted keratopigmentation double tunnel technique in the management of a case of Urrets-Zavalia syndrome.

PURPOSE: To describe the successful use of a double intrastromal tunnel femtosecond-assisted keratopigmentation technique to manage a case of unilateral Urrets-Zavalia syndrome. METHODS: A 33-year-old man was referred with a history of trauma in his right eye due to a labor-related accident. Because of myopic anisometropia, he had been previously implanted with an angle-supported phakic intraocular lens. The patient presented iris atrophy and a fixed dilated pupil. He complained of severe and incapacitating photophobia, glare, and decreased vision. To obtain a complete iris replica, the surgery involved creation of double keratopigmented intrastromal tunnels using femtosecond laser and micronized mineral pigments. The deepest layer was stained black first and then the superficial layer was stained with a contoured greenish blue-gray color, which matched the contralateral eye. RESULTS: In the immediate postoperative period, the patient reported a complete elimination of photophobia associated with the corrected distance visual acuity improvement. A very adequate cosmetic outcome was also achieved. Stability was observed during the 12-month follow-up. CONCLUSION: A femtosecond-assisted keratopigmentation technique using 2 pigmented intrastromal tunnels to achieve an intracorneal pigmented replica of the iris was effective in improving the patient's severe visual function disability and cosmetic appearance. To the best of our knowledge, this is the first report of severe visual function disability caused by atrophic iris and a fixed dilated pupil treated with double intrastromal layers of keratopigmentation by means of femtosecond-created tunnels.

Functional validation of the carbon dioxide receptor genes in Aedes aegypti mosquitoes using RNA interference.

Carbon dioxide (CO(2)) is an important long-range chemosensory cue used by blood-feeding female mosquitoes to find their hosts. The CO(2) receptor in Drosophila melanogaster was previously determined to be a heterodimer comprised of two gustatory receptor (Gr) proteins, DmGr21a and DmGr63a. In the mosquito Aedes aegypti, two putative orthologous genes, AaGr1 and AaGr3, were identified in the genome database, along with an apparent paralogue of AaGr1, AaGr2. In this study, RNA interference (RNAi)-mediated gene knockdown of either AaGr1 or AaGr3 resulted in a loss of CO(2) sensitivity in both male and female mosquitoes, suggesting that these two proteins, like the Drosophila orthologues, function as a heterodimer. RNAi-mediated knockdown of AaGr2 expression had no impact on CO(2) reception. All three Gr genes were expressed in the maxillary palps of both Ae. aegypti and the West Nile virus vector mosquito, Culex pipiens quinquefasciatus. Interestingly, expression of the two CO(2) receptor genes was not equivalent in the two sexes and the implications of differential sex expression of the CO(2) receptor in different species are discussed. The functional identification of the CO(2) receptor in a mosquito could prove invaluable in the strategic design of compounds that disrupt the mosquito's ability to find hosts.

Femtosecond-assisted keratopigmentation for functional and cosmetic restoration in essential iris atrophy.

UNLABELLED: We describe a new surgical technique of femtosecond-assisted keratopigmentation (KTP) in a 23-year-old woman with severe visual dysfunction secondary to unilateral essential iris atrophy due to the presence of iridocorneal endothelial syndrome in her left eye. The patient presented with complaints of photophobia and monocular diplopia in the affected eye. Femtosecond-assisted KTP surgery was performed in this eye. Following the procedure, the patient reported complete elimination of photophobia and diplopia, with an excellent cosmetic result. Follow-up of 12 months was unremarkable. To our knowledge, this is the first report of a severe visual function disability caused by essential iris atrophy that was corrected by a new KTP technique. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Keratopigmentation (corneal tattooing) for the management of visual disabilities of the eye related to iris defects.

AIM: To investigate the functional and cosmetic outcomes of keratopigmentation (KTP) in cases of moderate to severe visual dysfunctions owing to different iris disorders. METHODS: 11 eyes with moderate to severe visual disabilities related to iris defects underwent KTP for functional and cosmetic restoration using micronised mineral pigments and assisted with modern technologies such as femtosecond laser and new automated keratopigmentation instruments for the intrastromal and superficial application of the pigments. RESULTS: Following the KTP surgery, the visual-function-related symptoms improved in all cases, from significant improvement to total elimination. Eight patients were asymptomatic after the surgery. In two patients, minimal non-disabling symptoms remained after surgery. One patient with traumatic aniridia complained of significant residual glare at the 3-month postoperative visit and was reoperated to reduce the simulated pupil to 4 mm. The cosmetic outcomes were analysed and classified as excellent in eight patients and good in three. CONCLUSION: KTP using new micronised mineral pigments and new surgical protocols has proven in this series to be an effective surgical technique for the management of moderate to severe visual dysfunctions related to iris defects.

Cross-linking in progressive keratoconus using an epithelial debridement or intrastromal pocket technique after previous corneal ring segment implantation.

PURPOSE: To evaluate and compare the clinical and confocal microscopic outcomes achieved with two different procedures for cross-linking (CXL) in eyes with keratoconus: CXL with epithelial debridement and CXL with intrastromal pocket. METHODS: This retrospective study included 27 eyes of 21 patients (age range: 18 to 53 years) diagnosed with keratoconus who underwent implantation of intracorneal ring segments and CXL with two different techniques: CXL with previous epithelial debridement (classic group, 16 eyes) and CXL with intrastromal pocket for riboflavin infusion (pocket group, 11 eyes). Visual, refractive, topographic, aberrometric, and pachymetric data were evaluated during 12-month follow-up. RESULTS: No statistically significant differences between the classic and pocket groups were found in postoperative visual acuity (P ≥.71), refraction (P ≥.15), keratometry (P ≥.28), corneal aberrations (P ≥.13), or central pachymetry (P ≥.21). A statistically significant improvement in uncorrected visual acuity found at 3 months postoperatively in both groups (P<.03) was consistent with a change in manifest sphere. Mean keratometric reduction at 12 months was 0.03 diopters (D) in the classic group (P=.55) and 0.40 D in the pocket group (P=.05). No significant changes in corneal higher order aberrations or central corneal thickness were found in either group (P ≥.14). CONCLUSIONS: Cross-linking surgery with creation of an intrastromal pocket seems to provide similar clinical outcomes compared to the classic CXL technique.

Phakic intraocular lens implantation for treatment of anisometropia and amblyopia in children: 5-year follow-up.

PURPOSE: To evaluate the safety and efficacy during 5-year follow-up of phakic intraocular lens (PIOL) implantation to correct high anisometropia in amblyopic children who were non-compliant with traditional medical treatment including spectacles or contact lenses. METHODS: Retrospective study of 10 eyes of 10 children with high anisometropia who underwent PIOL implantation (9 with an iris-supported IOL and 1 with a posterior chamber IOL). Patient age at the time of implantation ranged from 2 to 15 years. Mean preoperative spherical equivalent refraction was -10.14 ± 6.96 diopters (D) (range: +8.00 to -18.00 D). Mean logMAR corrected distance visual acuity (CDVA) was 0.84 ± 0.52. Postoperative data at 6, 24, and 60 months were evaluated. RESULTS: Corrected distance visual acuity improved in all children. At 24 months, logMAR CDVA was 0.39 ± 0.35 and at 5 years was 0.36 ± 0.38 (range for both: 0.1 to 1.0) (P=.01). Improvement of more than three logMAR lines of CDVA was achieved in all children except for one (one line improvement) who was implanted with a posterior chamber PIOL. No loss of CDVA was detected in any patient. Five years after surgery, endothelial cell count was >2000 cells/mm(2) in eight (80%) patients; for the remaining two patients, one reported frequent eye rubbing and the other suffered ocular trauma. CONCLUSIONS: Phakic IOL implantation in children with anisometropic amblyopia showed a positive long-term impact on visual acuity.

Increased de novo copy number variants in the offspring of older males.

The offspring of older fathers have an increased risk of neurodevelopmental disorders, such as schizophrenia and autism. In light of the evidence implicating copy number variants (CNVs) with schizophrenia and autism, we used a mouse model to explore the hypothesis that the offspring of older males have an increased risk of de novo CNVs. C57BL/6J sires that were 3- and 12-16-months old were mated with 3-month-old dams to create control offspring and offspring of old sires, respectively. Applying genome-wide microarray screening technology, 7 distinct CNVs were identified in a set of 12 offspring and their parents. Competitive quantitative PCR confirmed these CNVs in the original set and also established their frequency in an independent set of 77 offspring and their parents. On the basis of the combined samples, six de novo CNVs were detected in the offspring of older sires, whereas none were detected in the control group. Two of the CNVs were associated with behavioral and/or neuroanatomical phenotypic features. One of the de novo CNVs involved Auts2 (autism susceptibility candidate 2), and other CNVs included genes linked to schizophrenia, autism and brain development. This is the first experimental demonstration that the offspring of older males have an increased risk of de novo CNVs. Our results support the hypothesis that the offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism by generation of de novo CNVs in the male germline.

Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmatics.

BACKGROUND: Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. OBJECTIVES: The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. METHODS: A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. RESULTS: At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of -78% and -57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. CONCLUSIONS: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma

Smoking and alcoholism target genes associated with plasticity and glutamate transmission in the human ventral tegmental area.

Drugs of abuse including nicotine and alcohol elicit their effect by stimulating the mesocorticolimbic dopaminergic system. There is a high incidence of nicotine dependence in alcoholics. To date only limited data is available on the molecular mechanism underlying the action of alcohol and nicotine in the human brain. This study utilized gene expression screening to identify genes sensitive to chronic alcohol abuse within the ventral tegmental area (VTA) of the human brain. Alcohol-responsive genes encoded proteins primarily involved in structural plasticity and neurotransmitter transport and release. In particular, genes involved with brain-derived neurotrophic factor signalling and glutamatergic transmission were found to be affected. The possibility that glutamate transport was a target of chronic alcohol and/or tobacco abuse was further investigated in an extended case set by measurement of mRNA and protein expression. Expression levels of vesicular glutamate transporters SLC17A6 and SLC17A7 were robustly induced by smoking, an effect that was reduced by alcohol co-exposure. Glutamatergic transmission is vital for the control of the VTA and may also be critical to the weighting of novelty and importance of a stimulus, an essential output of this brain region. We conclude that enduring plasticity within the VTA may be a major molecular mechanism for the maintenance of smoking addiction and that alcohol, nicotine and co-abuse have distinct impacts on glutamatergic transmission with important implications for the control of this core mesolimbic structure.

Does marathon running cause acute lesions of the knee? Evaluation with magnetic resonance imaging.

An investigation was conducted into whether running a marathon causes acute alterations in menisci, cartilage, bone marrow, ligaments, or joint effusions, which could be evaluated by magnetic resonance imaging (MRI). Twenty-two non-professional marathon runners underwent MRI of the knee before and immediately after running a marathon. Lesions of menisci and cartilage (five-point scale), bone marrow, ligaments (three-point scale), joint effusion, and additional findings were evaluated and a total score was assessed. Before the marathon, grade 1 lesions of the menisci were found in eight runners, and grade 2 lesions in five runners. After the marathon, an upgrading from a meniscal lesion grade 1 to grade 2 was observed in one runner. Before the marathon, grade 1 cartilage lesions were found in three runners, and grade 2 lesions in one runner, all of which remained unchanged after the marathon. Before and after the marathon, unchanged bone marrow edema was present in three runners and unchanged anterior cruciate ligament lesions (grade 1) were seen in two runners. Joint effusions were present in 13 runners in the pre-run scans, slightly increased in four runners after the marathon, and newly occurred in one runner after the marathon. A total score comprising all knee lesions in each runner showed an increase after the marathon in two runners, whereas no runner showed an improvement of the radiological findings (Wilcoxon signed-rank test, P>0.05). The evaluation of lesions of the knee with MRI shows that marathon running does not cause severe, acute lesions of cartilage, ligaments, or bone marrow of the knee in well-trained runners. Only subtle changes, such as joint effusions or increased intrameniscal signal alterations, were imaged after running a marathon.