\n\nThe in vitro permeation model developed in this study predicts the fraction absorbed of the selected drugs in humans within experimental uncertainty. It has been demonstrated that the correlation with the fraction absorbed is greatly

improved using the permeability data obtained under controlled hydrodynamics with paracellular transport included in the model. (C) 2011 Elsevier B.V. All rights reserved.”
“Physiological ecologists have long sought to understand the plasticity of organisms in environments that vary widely among years, seasons and even hours. This is now even more important because human-induced climate change is predicted to affect both the mean and variability of the thermal environment. Although environmental change occurs ubiquitously,

relatively few researchers have studied the effects of fluctuating environments on the performance of developing organisms. Even fewer have tried to MCC950 concentration validate a framework for predicting performance in fluctuating Selleckchem Epacadostat environments. Here, we determined whether reaction norms based on performance at constant temperatures (18, 22, 26, 30 and 34 degrees C) could be used to predict embryonic and larval performance of anurans at fluctuating temperatures (18-28 degrees C and 18-34C). Based on existing theory, we generated hypotheses about the effects of stress and acclimation on the predictability of performance in variable environments. Our empirical models poorly predicted the performance of striped marsh frogs (Limnodynastes peronii) at fluctuating temperatures, suggesting that extrapolation from studies conducted under artificial thermal conditions would lead to erroneous conclusions. During the majority of ontogenetic stages, growth and development in variable environments proceeded more rapidly than expected, suggesting

that acute PI3K inhibitor exposures to extreme temperatures enable greater performance than do chronic exposures. Consistent with theory, we predicted performance more accurately for the less variable thermal environment. Our results underscore the need to measure physiological performance under naturalistic thermal conditions when testing hypotheses about thermal plasticity or when parameterizing models of life-history evolution.”
“Chlorophenols (CPs) have been suspected to disrupt the endocrine system and thus affect human and wildlife reproduction but less is known about the underlying mechanism. In this study, we investigated the effects of pentachlorophenol (PCP) and 2.4,6-trichlorophenol (TCP) on human adrenocortical carcinoma cell line (H295R). The H295R cells were exposed to environmentally relevant concentration (0.0, 0.4, 1.1,3.4 mu M) of PCP and TCP for 48 h, and expression of specific genes involved in steroidogenesis, including cytochrome P450 (CYP11A,CYP17,CYP19),3 beta HSD2,17 beta HSD4 and StAR was quantitatively measured using real-time polymerase chain reaction. The selected gene expressions were significantly down-regulated compared with those in the control group.

“
“Over the past decade, comprehensive genomic studies demonstrated that leiomyosarcomas and most of the tumors previously labeled as ‘malignant fibrous histiocytomas’ share complex karyotypes and genomic profiles, and can be referred to as ‘sarcomas with complex genomics’. We recently reported a series of 160 sarcomas with complex genomics such as leiomyosarcomas, myxofibrosarcomas, Nepicastat ic50 pleomorphic liposarcomas/rhabdomyosarcomas and undifferentiated pleomorphic sarcomas. These tumors present with a frequent loss of chromosome 10 region encompassing

the tumor suppressor gene PTEN. In the present study, we assessed PTEN genomic level and protein expression in this large series of sarcomas with complex genomics, as well as activation of downstream pathways. PTEN partial genomic loss was observed in only 46% of tumors, especially in well-differentiated leiomyosarcomas, whereas up to 68% of these tumors demonstrate a loss of protein expression

SNS-032 chemical structure on western blot analysis. Specific discrepancies in PTEN immunohistochemical results suggested bias in this latter technique. PTEN mutations were rare, with only 4 point mutations in the 65 samples studied. Subsequent activation of AKT and mTOR pathways was only observed in 2 out of 3 of PTEN-deleted tumors. On the other hand, RICTOR, a major component of the mTOR complex 2, was significantly overexpressed in well-differentiated leiomyosarcomas. These results, confirmed on tissue micro-array immunohistochemical analysis

of 459 sarcomas, could suggest a link between RICTOR overexpression and leiomyosarcomas oncogenesis. As therapeutics directed against the mTOR pathway are assessed in sarcomas, RICTOR overexpression in sarcomas and its links to therapeutic response need to be assessed. Modern Pathology (2012) 25, 197-211; doi:10.1038/modpathol.2011.163; published online 11 November 2011″
“The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) contribute to the regulation of diverse cognitive and physiological functions including nociception. Indeed, OXT has been reported to be analgesic when administered directly into the brain, the spinal cord, or systemically. Here, we characterized the phenotype of oxytocin receptor (OTR) and vasopressin-1A Selleck BMS345541 receptor (V1AR) null mutant mice in a battery of pain assays. Surprisingly, OTR knock-out mice displayed a pain phenotype identical to their wild-type littermates. Moreover, systemic administration of OXT dose-dependently produced analgesia in both wild-type and OTR knock-out mice in three different assays, the radiant-heat paw withdrawal test, the von Frey test of mechanical sensitivity, and the formalin test of inflammatory nociception. In contrast, OXT-induced analgesia was completely absent in V1AR knock-out mice. In wild-type mice, OXT-induced analgesia could be fully prevented by pretreatment with a V1AR but not an OTR antagonist.

3 (3)degrees. Intramolecular O-H center dot center dot center dot N and O-H center dot center dot center dot Br interactions are observed in the benzohydrazide molecule. In the crystal, pairs of adjacent benzohydrazide molecules are linked by two methanol molecules through intermolecular O-H center dot center dot center dot O and N-H center dot center dot center dot O hydrogen bonds, forming a dimer.”
“Biosynthesis of cysteine is one of the fundamental processes in plants providing the reduced sulfur for cell metabolism. It is accomplished by the sequential action of two enzymes, serine acetyltransferase (SAT) and Selleck Bcl2 inhibitor O-acetylserine (thiol) lyase (OAS-TL). Together they constitute the hetero-oligomeric

cysteine synthase (CS) complex through specific protein-protein interactions influencing the rate BMS-754807 solubility dmso of cysteine production. The aim of our studies was to deregulate the CS complex formation in order to investigate its function in the control of sulfur homeostasis and optimize cysteine synthesis. Computational modeling was used to build a model of the Arabidopsis thaliana mitochondrial

CS complex. Several polypeptides based on OAS-TL C amino-acid sequence found at SAT-OASTL interaction sites were designed as probable competitors for SAT3 binding. After verification of the binding in a yeast two-hybrid assay, the most strongly interacting polypeptide was introduced to different cellular compartments of Arabidopsis cell via genetic transformation. Moderate increase in total SAT and OAS-TL activities, but not thiols content, was observed dependent on the transgenic line and sulfur availability in the hydroponic medium. Though

our studies demonstrate the proof of principle, they also suggest more complex interaction of both enzymes underlying the mechanism of their reciprocal regulation. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“In the Tokat and Sivas provinces of Turkey, the overall Crimean-Congo hemorrhagic fever virus (CCHFV) seroprevalence was 12.8% among 782 members of a high-risk population. CCHFV seroprevalence was associated with history of tick bite or tick removal from animals, employment in animal husbandry or farming, and being > 40 years of age.”
“Objectives: We determined the feasibility and check details optimization of differentiating human induced pluripotent stem cells (hiPS) into nonkeratinized stratified squamous epithelial cells for vocal fold engineering. Methods: hiPS were cultured and assessed for differentiation in 3 conditions: a 3-dimensional (3D) hyaluronic acid (HA) hydrogel scaffold, a 3D HA hydrogel scaffold with epidermal growth factor (EGF), and a 3D HA hydrogel scaffold co-cultured with human vocal fold fibroblasts (hVFF). After 1, 2, and 4 weeks of cultivation, hiPS were selected for histology, immunohistochemistry, and/or transcript expression analysis.

The results indicate that a chain of 4000 g mol(-1) is sufficient to represent the second sphere effect in our model. Although the activation entropy Delta S-double dagger was significantly increased, the k(cat) value was not increased, due to unfavorable changes in Delta H-double dagger. The dinuclear catalytic center remained intact, acting through the same mechanism, which opens new possibilities for the rational functionalization at this chain length to further increase the complex activity. (C) 2014 Elsevier B.V. All rights reserved.”
“The

adaptive arm of the immune system has been suggested as an important BTSA1 chemical structure factor in brain function. However, given the fact that interactions of neurons or glial cells with T lymphocytes rarely occur within the healthy CNS parenchyma, the underlying mechanism is still a mystery. Here we found that at the interface between the brain and blood circulation, the epithelial layers of the choroid plexus (CP) are constitutively populated with CD4(+) effector memory cells with a T-cell receptor repertoire

specific to CNS antigens. Sotrastaurin With age, whereas CNS specificity in this compartment was largely maintained, the cytokine balance shifted in favor of the T helper type 2 (Th2) response; the Th2-derived cytokine IL-4 was elevated in the CP of old mice, relative to IFN-gamma, which decreased. We found this local cytokine shift to critically affect the CP epithelium, triggering it to produce the chemokine CCL11 shown to be associated with cognitive dysfunction.

Partial restoration of cognitive ability in aged mice, by lymphopenia-induced homeostasis-driven proliferation of memory T cells, was correlated with restoration of the IL-4:IFN-gamma ratio at the CP and modulated the expression of plasticity-related genes SHP099 in vitro at the hippocampus. Our data indicate that the cytokine milieu at the CP epithelium is affected by peripheral immunosenescence, with detrimental consequences to the aged brain. Amenable to immunomodulation, this interface is a unique target for arresting age-related cognitive decline.”
“Background: Outcome quality indicators are rarely used to evaluate mental health services because most jurisdictions lack clinical data systems to construct indicators in a meaningful way across mental health providers. As a result, important information about the effectiveness of health services remains unknown. This study examined the feasibility of developing mental health quality indicators (MHQIs) using the Resident Assessment Instrument Mental Health (RAI-MH), a clinical assessment system mandated for use in Ontario, Canada as well as many other jurisdictions internationally.\n\nMethods: Retrospective analyses were performed on two datasets containing RAI-MH assessments for 1,056 patients from 7 facilities and 34,788 patients from 70 facilities in Ontario, Canada.

In agreement with our expectations, the uncoupling treatment increased metabolic rate. However, we found no evidence that treated birds enjoyed lower oxidative stress levels or greater survival rates, in contrast to previous results in other taxa. In vitro experiments revealed lower sensitivity of ROS production to DNP in mitochondria isolated from skeletal muscles of zebra finch than mouse. In addition, we found significant reductions in the number of eggs laid and in the inflammatory

immune response in treated birds. Altogether, our data suggest that the ‘uncoupling to survive’ hypothesis may not be applicable for zebra finches, presumably because of lower effects of mitochondrial uncoupling on mitochondrial ROS production in birds than in mammals. Nevertheless, mitochondrial uncoupling appeared to be a potential life-history regulator of traits such as https://www.selleckchem.com/products/U0126.html fecundity MK-8776 datasheet and immunity at adulthood, even with food supplied ad libitum.”
“ObjectiveThe long-term effects of traumatic brain injury (TBI) can resemble observed in normal ageing, suggesting that TBI may accelerate the ageing process. We investigate this using a neuroimaging model that predicts

brain age in healthy individuals and then apply it to TBI patients. We define individuals’ differences in chronological and predicted structural “brain age,” and test whether TBI produces progressive atrophy and how this relates to cognitive function. MethodsA predictive model of normal ageing was defined using machine learning in 1,537 healthy individuals, based on magnetic resonance imaging-derived estimates of gray matter (GM) and white matter AS1842856 inhibitor (WM). This ageing model was then applied to test 99 TBI patients and 113 healthy controls to estimate brain age. ResultsThe initial model accurately predicted age in healthy individuals

(r=0.92). TBI brains were estimated to be “older,” with a mean predicted age difference (PAD) between chronological and estimated brain age of 4.66 years (10.8) for GM and 5.97 years (+/- 11.22) for WM. This PAD predicted cognitive impairment and correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase. InterpretationTBI patients’ brains were estimated to be older than their chronological age. This discrepancy increases with time since injury, suggesting that TBI accelerates the rate of brain atrophy. This may be an important factor in the increased susceptibility in TBI patients for dementia and other age-associated conditions, motivating further research into the age-like effects of brain injury and other neurological diseases. Ann Neurol 2015;77:571-581″
“Sinorhizobium meliloti infects leguminous plants resulting in a nitrogen-fixing symbiosis. Free living cells accumulate poly(3-hydroxybutyrate) (PHB) as carbon and energy source under imbalanced growth conditions.

“
“We identified the soldier-specific compounds in the Japanese subterranean termite, Reticulitermes speratus, to clarify their ethological roles. Silica gel column chromatography separated one major soldier-specific compound in the hexane fraction accounting for 70-80% of the total amount of the fraction, while cuticular hydrocarbons constituted the rest. We identified the compound NVP-AUY922 Cytoskeletal Signaling inhibitor as beta-selinene by gas chromatography-mass spectrometry (GC-MS) and nuclear

magnetic resonance (NMR) spectroscopy. Comparative GC analyses of the major exocrine glands detected the compound in the soldier’s frontal gland. Both soldiers and workers made aggregation to the hexane fraction, as well as to the crushed heads and head extract of the soldiers. They did not aggregate to cuticular hydrocarbons, making it likely that beta-selinene was the aggregation pheromone in this species. The opportunistic predator of this

termite, Lasius japonicus, was also attracted to the compounds. The ant workers, therefore, would use the termite aggregation pheromone as a kairomone for hunting them.”
“Photoacoustic microscopy (PAM) has achieved submicron lateral resolution in showing subcellular structures; however, relatively few endogenous subcellular contrasts have so far been imaged. Given that the hemeprotein, mostly cytochromes in general cells, is optically absorbing around the Soret selleck compound peak (similar to 420 nm), we implemented label-free PAM of cytochromes in cytoplasm for the first time. By measuring the photoacoustic spectra of the oxidized and reduced states of fibroblast lysate and fitting the difference spectrum with three types of cytochromes, we found that the three cytochromes account for more than half the optical absorption in the cell lysate at 420 nm wavelength. Fixed fibroblasts on slides

were imaged by PAM at 422 and 250 nm compound inhibitor wavelengths to reveal cytoplasms and nuclei, respectively, as confirmed by standard staining histology. PAM was also applied to label-free histology of mouse ear sections by showing cytoplasms and nuclei of various cells. PAM of cytochromes in cytoplasm is expected to be a high-throughput, label-free technique for studying live cell functions, which cannot be accomplished by conventional histology. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE) [DOI: 10.1117/1.JBO.18.2.020504]“
“Motivation: Systematic identification of microRNA ( miRNA) targets remains a challenge. The miRNA overexpression coupled with genome-wide expression profiling is a promising new approach and calls for a new method that integrates expression and sequence information.\n\nResults: We developed a probabilistic scoring method called targetScore. TargetScore infers miRNA targets as the transformed fold-changes weighted by the Bayesian posteriors given observed target features. To this end, we compiled 84 datasets from Gene Expression Omnibus corresponding to 77 human tissue or cells and 113 distinct transfected miRNAs.

“
“Purpose: Although varicose veins are very common in adults, the mechanism of the disease has not been established. Degradation of the extracellular matrix

is regulated by various matrix metallopreteinases (MMPs) and their inhibitors tissue GSK1838705A order inhibitor of metallaproteinase (TIMPs). This study was performed to analyse the relationship between venous wall degeneration and expression of these matrix proteinases.\n\nMethods: Twelve great saphenous vein (GSV) segments from 7 patients without varicose veins (control) and 86 GSV segments from 18 patients (22 limbs) with varicose veins (C(2,4,5)E(P)A(S)P(R)) were used for this study. Light microscopic examination was used in the evaluation of vein wall degeneration, immunohistochemistry and Western blotting for the expression of MMPs (MMP-1, MMP-2, MMP-9 and MMP-13) and TIMPs (TIMP-1 and TIMP-2), and zymography for gelatinolytic activity of MMP-2 and MMP-9

were performed.\n\nResults: MMP-9 was more strongly expressed in the vein wall of both control and patient groups, especially in the endothelial cells and medial muscle layers and TIMP-2 followed. The expression of MMP-9 was closely related to the degree of venous wall degeneration. Activated MMP-2 and MMP-9 were observed in JQ1 Epigenetics inhibitor both groups and expressed more in the proximal GSV of the patients. In the Western blotting, the expression of MMP-9 and TIMP-1 were significantly higher than other MMPs and TIMP-2 in the patients with varicose veins.\n\nConclusion: MMP-9 is selleck kinase inhibitor much more expressed in the wall of degenerative veins. This matrix-degrading enzyme may play an important role in the degeneration of venous wall followed by its remodeling. (J Korean Surg Soc 2010;79:S16-25)”
“Objective: To examine the prevalence and biopsychosocial predictors of suboptimal virologic response to highly active antiretroviral therapy (HAART) among human immunodeficiency virus-infected

adolescents.\n\nDesign: Population-based cohort study.\n\nSetting: Sixteen academic medical centers across 13 cities in the United States.\n\nParticipants: One hundred fifty-four human immunodeficiency virus-infected adolescents who presented for at least 2 consecutive visits after initiation of HAART.\n\nMain Outcome Measures: Viral load (plasma concentration of human immunodeficiency virus RNA) and CD(4+) lymphocyte count.\n\nResults: Of the 154 adolescents enrolled in the study, 50 (32.5%) demonstrated early and sustained virologic suppression while receiving HAART. The remaining 104 adolescents (67.5%) had a poor virologic response. Adequate adherence (>50%)-reported by 70.8% of respondents-was associated with 60% reduced odds of suboptimal virologic suppression in a multivariable logistic regression model (adjusted odds ratio=0.4; 95% confidence interval, 0.2-1.0). Exposure to suboptimal antiretroviral therapy prior to HAART, on the other hand, was associated with more than 2-fold increased odds of suboptimal virologic response (adjusted odds ratio=2.

05). The percentages of subjects infected with HIV-1C and recombinant subtypes did not change significantly. Over this 8-year period, GSK1838705A supplier the overall viral population in this region evolved toward the less virulent HIV-1A strain, most likely as a consequence of the faster disease progression and lower transmissibility of HIV-1D.”
“Cutaneous drug reactions are the most common type of adverse drug reaction. These reactions, ranging from simple pruritic eruptions to potentially life-threatening events, are a significant cause of iatrogenic morbidity and mortality. Stevens-Johnson syndrome (SJS) is a serious and potentially life-threatening cutaneous drug reaction.

Although progress has been made in the management of SJS through early detection, prompt hospitalization, and immediate cessation of offending agents, the prevalence of permanent disabilities associated with SJS remains unchanged. Nevertheless, despite being a problem that is global in scope, government and health care agencies worldwide have yet to find

a consensus on either diagnostic criteria or therapy for this disorder. Here, we provide the internist and emergency room physician with a brief review the SJS literature and summarize the latest recommended interventions with the hope of improving early recognition of this disease see more and prevention of permanent sequelae and mortality that frequently complicate SJS.”
“This work reports the effect of stiffness and conformation of chain-like polymers on wrapping behaviors around single-walled carbon nanotubes (SWNT). As a model of chain-like polymers, three kinds of poly(dialkylsilane) (PSi)s with random-coiled, flexible, and semiflexible main chains were employed. Complexes of PSi and SWNT were prepared using mechanochemical

high-speed vibration milling (HSVM). Stiffness-dependent polymer wrapping behaviors were investigated using combinational analyses with a differential scanning calorimeter, transmission electron microscopy, ZD1839 solubility dmso and atomic force microscopy, Furthermore, the conformational behaviors of the PSi’s wrapped onto SWNTs were characterized spectroscopically with ordinary UV spectroscopy. Random-coiled and flexible PSi’s were successfully wrapped onto small bundles of SWNTs, in which their conformations were changed to fit the surface curvatures of the SWNTs. However, semiflexible PSi could not form a complex with SWNTs, and its conformation remained unchanged even after the same HSVM process. Knowledge gained from this study may lead to a new approach to molecular design of chain-like polymers for efficient wrapping materials for SWNTs.”
“AIM: To evaluate the association between 25-hydroxyvitamin D [25(OH)D] and sustained virological response (SVR) in hepatitis C virus (HCV) infected individuals.

5[6.8-13.0] mg/l, p<0.01) and DLP4 (10.1[7.4-16.8] mg/l, p<0.01) after adjustment for age, sex

and body mass index were found. Adiponectin correlated positively with high-density lipoprotein cholesterol and apolipoprotein A1 (apoA1), negatively with triglycerides, apoB/apoA1, high-sensitivity C-reactive protein, insulin, homeostasis model assessment and waist circumference. ApoA1 and insulin were detected as independent predictors for adiponectin levels in multivariate regression analysis. Adiponectin did not correlate with IMT.\n\nConclusions. Individuals with hypertriglyceridemic phenotypes selleckchem showed decreased adiponectin levels in comparison with normolipidemic subjects. Adiponectin was associated with lipid

parameters, markers of insulin resistance, chronic inflammation and visceral obesity. But no association between adiponectin and IMT was found.”
“Despite the growing importance of ethyl glucuronide (EtG) in hair for detection of chronic excessive alcohol consumption, the mechanism of incorporation is not yet GSK690693 datasheet clear. Deposition from sweat is believed to be the main route. In order to get more information, EtG was determined in daily shaved beard hair after single higher alcohol doses.\n\nThree volunteers drank within 5.5 h 153, 165 and 200 g ethanol followed by abstinence. Daily shaved beard hair was analysed for EtG using a validated liquid chromatography-tandem mass spectrometry method with a limit of quantification of 2 pg/mg.\n\nFor all three volunteers, small concentrations of EtG were already detected 9 h after end of drinking. The concentrations increased to maxima of 182, 242 and 74

pg/mg on days 2 to 4 and then gradually decreased to limit of quantification on days 8 to 10.\n\nThe time course of EtG is discussed based on literature data about anatomic dimensions of the hair root, physiology of hair growth, kinetics of EtG formation and elimination in blood, and in comparison to literature results about drugs in beard hair. It follows that for beard hair the predominant portion of EtG is incorporated in the upper part of the hair root between suprabulbar region and isthmus leading to a Z-VAD-FMK mouse positive zone of about 3 mm (8-9 days) after a single drinking event. Deposition from sweat which is only possible into the residual hair stubble after shaving and in the infundibulum down to the sebaceous gland mouth was found to be of minor importance but could play a greater role in long hair.\n\nIt is concluded that EtG in hair fulfils the prerequisites for time-resolved interpretation of segmental concentrations and that a single excessive drinking can be well detected in sufficiently short hair segments. However, in the routinely investigated 3-cm proximal scalp hair segment and using the cutoff of 7 pg/mg, a negative result can be expected with high probability because of dilution by negative hair.

Fertilized ovule development was associated with increased IAA levels 21-24 days after pollination, followed by a sharp decrease in the cotyledonary stage, both in zygotic and somatic embryos. There was a prominent increase in ABA levels in cultures which generated ISE 24-30 days after pollination, a period that corresponds to the heart and

torpedo stages. The levels of total CKs (Z, [9R]Z, iP and [9R]iP) were also always higher in zygotic than in somatic embryogenesis. While zygotic embryogenesis was dominated by the presence of zeatin, the somatic process, contrarily, was characterized by a large variation of the other cytokinin forms and amounts studied. The above results, when taken together, could be related to the previously observed high selleck compound frequency formation of anomalous somatic embryos formed in A. sellowiana, as well as to their low germination ability.”
“In this study, TiCl4 coagulant together with coagulant aids such as FeCl3, Al-2 (SO4)(3), and Ca(OH)(2) were investigated to improve the photoactivity of titanium dioxide (TiO2) produced from sludge and to increase the resulting low pH value. After TiCl4 flocculation with three coagulant aids, the settled

floc (sludge) was incinerated at 600 degrees C to produce TiO2 doped with Fe, Al, and Ca elements. Fe-, Al-, and Ca-doped TiO2 was characterized in terms of structural, chemical, and photo-electronic properties. All the coagulant aids used together with Ti-salt flocculation effectively increased the pH values. CDK inhibitor The surface area of TiO2-WO (without any coagulant aids), Fe/TiO2, Al/TiO2, and Ca/TiO2 was 122 m(2)/g, 77 m(2)/g, 136 m(2)/g and 116 m(2)/g, respectively. The TiO2-WO, Fe/TiO2, Al/TiO2, and Ca/TiO2 was found to be of anatase phase. The XRD pattern on the Fe/TiO2 included an additional peak of hematite (alpha-Fe2O3). The majority of gaseous acetaldehyde with TiO2-WO and Ca/TiO2 for photocatalytic activity was completely

removed within 40 minutes under UV irradiation.”
“Introduction. Methotrexate see more is an antifolate medication frequently used in the treatment of malignant and nonmalignant diseases. The usage of high-dose methotrexate was limited to patients with osteosarcoma, Ewing sarcoma, lymphoma, and acute lymphoblastic leukemia. One of the major side effects of high-dose methotrexate is nephropathy. The aim of present study was to determine the renal side effects of high-dose methotrexate in patients with malignancies.\n\nMaterials and Methods. In a study of 102 patients with osteosarcoma (n = 72), Ewing sarcoma (n = 15), and lymphoma (n = 15), treated with high-dose methotrexate, clinical and laboratory data including kidney function tests were recorded at baseline and during follow-up visits. The mean duration of follow-up was 6 months.\n\nResults. The mean age of the patients was 19.5 years (range, 5 to 80 years).