The predicted 3′-UTR of MMP-16, an activator of MMP-2 and -9, was cloned into the pMIR-REPORT vector and luciferase assays were performed. Introduction of miR-155 significantly reduced luciferase activity which selleck could be abolished by cotransfection with anti-miR-155 or target site mutagenesis. By using MMP-16 siRNA to reduce MMP-16 levels or by using an MMP-16 blocking antibody, hCMPC migration could be blocked as well. By directly targeting MMP-16, miR-155 efficiently inhibits cell migration via a reduction in MMP-2 and -9 activities. Our study shows that miR-155 might be used to improve local retention of hCMPCs after intramyocardial delivery.”
“The transforming growth factor-beta

(TGF-beta) signalling pathway participates in various biological processes. Dysregulation

of Smad4, a central cellular transducer of TGF-beta signalling, is implicated in a wide range of human diseases and developmental disorders. However, the mechanisms underlying Smad4 dysregulation are not fully understood. NVP-HSP990 Using a functional screening approach based on luciferase reporter assays, we identified 39 microRNAs (miRNAs) as potential regulators of Smad4 from an expression library of 388 human miRNAs. The screening was supported by bioinformatic analysis, as 24 of 39 identified miRNAs were also predicted to target Smad4. MiR-199a, one of the identified miRNAs, was inversely correlated with Smad4 expression in various human cancer cell lines and gastric cancer Selleckchem Vorinostat tissues, and repressed Smad4 expression and blocked canonical TGF-beta transcriptional responses in cell lines. These effects

were dependent on the presence of a conserved, but not perfect seed paired, miR-199a-binding site in the Smad4 3′-untranslated region (UTR). Overexpression of miR-199a significantly inhibited the ability of TGF-beta to induce gastric cancer cell growth arrest and apoptosis in vitro, and promoted anchorage-independent growth in soft agar, suggesting that miR-199a plays an oncogenic role in human gastric tumourigenesis. In conclusion, our functional screening uncovers multiple miRNAs that regulate the cellular responsiveness to TGF-beta signalling and reveals important roles of miR-199a in gastric cancer by directly targeting Smad4.”
“Strain L36, naturally resistant to the herbicide metsulfuron-methyl (SM), was isolated and characterized with respect to the molecular mechanism of resistance. The isolate was identified as Pseudomonas aeruginosa based on bacterial morphology, physiology, cellular fatty acid, and 16S rRNA gene sequence. Minimal inhibitory concentrations of metsulfuron-methyl against the growth of L36 and wild type isolate PAO1 were 6.03 and 1.33 mM, respectively. L36 carried a nucleotide base change in the acetolactate synthase (ALS) gene that coded for a single amino acid mutation (Ala29 -> Val29).

7% in males and 8.7% in females, p smaller than 0.001). Based on both low ferritin and raised sTfR ( bigger than 21nmol/ml) only 2.3% were iron-deficient. 3.0% and Selleck P005091 2.7% were found to have low levels of serum folate ( smaller than 2.3ng/ml) and serum B12 ( smaller than 120ng/l) respectively. Clinically significant macrocytosis (MCV bigger than 99fl) was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and

vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF) for macrocytosis associated with elevated GGT (25.0%) and smoking (24.6%) was higher than for excess alcohol intake (6.3%), folate deficiency (10.5%) or vitamin B12 (3.4%). Conclusions: Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland. Macrocytosis is more likely to be attributable to an elevated GGT and smoking than vitamin B12 or folate deficiency.”
“The energetics of protein homo-oligomerization was analyzed in detail with the application of a general thermodynamic model. We have studied the thermodynamic aspects of protein-protein interaction employing beta-lactoglobulin A

from bovine milk at pH=6.7 where the protein is mainly in its dimeric form. We performed differential calorimetric scans at different total protein concentration and the resulting thermograms were analyzed with the thermodynamic model for oligomeric proteins previously developed. The GSI-IX mouse thermodynamic model employed, allowed the prediction of the sign of the enthalpy of dimerization,

the analysis of complex calorimetric profiles without transitions baselines subtraction and the obtainment of the thermodynamic parameters from the unfolding and the association processes and the compared with association SN-38 DNA Damage inhibitor parameters obtained with Isothermal Titration Calorimetry performed at different temperatures. The dissociation and unfolding reactions were also monitored by Fourier-transform infrared spectroscopy and the results indicated that the dimer of beta-lactoglobulin (N-2) reversibly dissociates into monomeric units (N) which are structurally distinguishable by changes in their infrared absorbance spectra upon heating. Hence, it is proposed that p.-lactoglobulin follows the conformational path induced by temperature: N-2 (sic) 2N (sic) 2D. The general model was validated with these results indicating that it can be employed in the study of the thermodynamics of other homo-oligomeric protein systems. (C) 2011 Elsevier B.V. All rights reserved.”
“MicroRNAs (miRNAs) are a newly discovered endogenous class of small noncoding RNAs that play important posttranscriptional regulatory roles by targeting mRNAs for cleavage or translational repression.

Expression of the Capsicum annuum pathogenesis-related 4 gene was primed in response to pathogen infection as assessed by quantitative real-time PCR. The accumulation Danusertib ic50 of cucumber mosaic virus RNA was reduced in PABA-treated pepper plants at 40 and 105 d post-treatment. Unexpectedly, fruit yield was increased in PABA-treated plants, indicating that PABA-mediated SAR successfully protected pepper plants from infection by bacterial and

viral pathogens without significant fitness allocation costs.\n\nThe present study is the first to demonstrate the effective elicitation of SAR by a folate precursor under field conditions.”
“Predictions of climate change indicate an increase in water scarcity in Mediterranean areas. Therefore, improving water use efficiency (WUE) becomes crucial for sustainable viticulture in the Mediterranean for both grapevine growth

and fruit productivity. Variability of WUE between cultivars presents an opportunity to select the most appropriate cultivars in viticultural areas with increasing BMS-777607 aridity. In this review, an update on the variability of WUE in different grapevine cultivars and environmental conditions is presented. Most studies on WUE are focused at the leaf level and frequently used to estimate whole-plant WUE. However, there are large discrepancies when scaling-up WUE from leaf to whole-plant level. There are several structural and physiological processes, not included in leaf WUE measurements, considered as possible factors to solve the gap between leaf and whole-plant WUE. Canopy structure and plant respiration are described as the most important components Copanlisib involved in whole-plant WUE regulation, and proposed as potential targets for its improvement. (C) 2013 Elsevier B.V. All rights reserved.”
“Well

dispersed 45S5 Bioglass(A (R)) (BG)-graphene nanoplatelets (GNP) composites were prepared after optimising the processing conditions. Fully dense BG nanocomposites with GNP loading of 1, 3 and 5 vol% were consolidated using Spark plasma sintering (SPS). SPS avoided any structural damage of GNP as confirmed using Raman spectroscopy. GNP increased the viscosity of BG-GNP composites resulting in an increase in the sintering temperature by similar to 50 A degrees C compared to pure BG. Electrical conductivity of BG-GNP composites increased with increasing concentration of GNP. The highest conductivity of 13 S/m was observed for BG-GNP (5 vol%) composite which is similar to 9 orders of magnitude higher compared to pure BG. For both BG and BG-GNP composites, in vitro bioactivity testing was done using simulated body fluid for 1 and 3 days. XRD confirmed the formation of hydroxyapatite for BG and BG-GNP composites with cauliflower structures forming on top of the nano-composites surface.

Louis Children’s Hospital starting in November 2012. We analyzed demographic and clinical data from all patients smaller than 5 years of age with solo detection of HCoV-OC43 (n = 52) and HCoV-NL63 (n = 44) and for comparison, samples of children with respiratory syncytial virus, parainfluenza virus and picornaviruses. Results: During the study period, HCoV-OC43 (4%) was the 5th and HCoV-NL63 the 8th (2%) most common respiratory virus. Coinfections were detected in 35% and 38% of children with HCoV-OC43 and HCoV-NL63, respectively. Croup was more common with HCoV-NL63 (30%) than with HCoV-OC43 (2%). Lower respiratory tract infection occurred in 33% VX-770 order of children with HCoV-OC43 and 25% of children with

AZD5582 order HCoV-NL63. Severe illness was less common in HCoV-NL63, HCoV-OC43 and parainfluenza virus (14%, each) compared with respiratory syncytial virus (30%) and picornaviruses (26%; P = 0.055 for HCoVs combined compared with the other respiratory viruses) and occurred mainly in those with underlying medical conditions. Conclusions: Infections caused by HCoV-OC43 and HCoV-NL63 are common and include some

with lower respiratory tract involvement and severe disease, especially in children with underlying medical conditions. Overall, a substantial burden of disease associated with both HCoV-OC43 and HCoV-NL63 was observed for hospitalized children smaller than 5 years of age.”
“A 9-year old, debilitated, female teddy goat, with a body weight of about 23 kg, was subjected to smear staining, histopathological examination and ELISA for the diagnosis of Johne’s disease (JD). During postmortem, the intestine showed thick corrugated mucosa and the mesenteric lymph nodes were found enlarged and edematous. Acid fast bacilli of multibacillary form were detected in Ziehl-Neelsen stained smears prepared form the tissues which showed gross pathology. Histopathologically, the ileal mucosa was intensely infiltrated by mononuclear cells and one of the ileum-associated lymph node revealed

a large granuloma in its para cortical region. Special staining of tissue sections demonstrated the occurrence of acid fast bacilli. The JD case was confirmed by using indirect ELISA. The present case was differed from the previously reported studies in two Sotrastaurin ic50 aspects viz 1) A confirmed case of multibacillary form of JD in a teddy goat 2) Unusual presence of a large granuloma in the lymph node. (C)2012 PVJ. All rights reserved To Cite This Article: Sikandar A, AH Cheema, M Younus and H Zaneb, 2013. Mycobacterium avium subspecies paratuberculosis multibacillary infection (Johne’s disease) in a Teddy goat. Pak Vet J, 33(2): 259-261.”
“Very little is known about the biology of Catorhintha species, for which a total of 32 species are known, with 10 species present in Mexico. The aim of this work was to describe the immature stages of Catorhintha apicalis scrutator.

The position in SOS3 corresponding to the barley substitution does not participate directly in Ca2+ binding, post-translational

modifications or interaction Selleckchem BMN 673 with the SOS2 signalling partner. However, Thr111 but not Ala111 forms a predicted hydrogen bond with a neighbouring alpha-helix, which has potential implications for the overall structure and function of the barley protein. HvCBL4 therefore represents a candidate for HvNax4 that warrants further investigation.”
“The use of noninvasive ventilation (NIV) for acute respiratory failure has become widespread, but with the newfound beneficial treatments come complications. There is credible although somewhat disparate evidence to support the concept that, compared to invasive ventilation,

NIV can reduce the incidence of infectious complications. In selected populations, nosocomial pneumonia appears to be significantly less common with NIV than with endotracheal intubation. NIV complications Selleckchem Navitoclax range from minor (eg, mask-related difficulties) to serious (eg, aspiration and hemodynamic effects). Evidence shows that if NIV is inappropriately applied for too long, the consequences may lead to death, presumably due to excessive delay of intubation. Despite apparently similar costs of treatment for patients with equivalent severity of illness, there is substantially less reimbursement for NIV than for intubation. The use of sedation in NIV patients has not been systematically studied, and sedation is generally underutilized, to avoid complications. Do-not-intubate patients

pose a special ethical dilemma with regard to NIV, because NIV may conflict with a preexisting directive not to use life-support measures in the terminally ill patient.”
“Exponential expansion of human populations and human activities within primate habitats has resulted in high potential for pathogen exchange creating challenges for biodiversity conservation and global health. Under such conditions, resilient habitat see more generalists such as black and gold howler monkeys (Alouatta caraya) may act as effective sentinels to overall ecosystem health and alert us to impending epidemics in the human population. To better understand this potential, we examined noninvasively collected fecal samples from black and gold howler monkeys from remote, rural, and village populations in Northern Argentina. We examined all samples (n = 90) for the zoonotic protozoa Cryptosporidium sp. and Giardia sp. via immunofluorescent antibody (IFA) detection. All samples were negative for Cryptosporidium sp. The prevalence of Giardia sp. was significantly higher at the rural site (67%) compared with the remote forest (57%) and village (40%) sites. A lack of Cryptosporidium sp.

Unlike the engineered this website macroscopic structures that we commonly build, biological structures are dynamic and self-organize: they sculpt themselves and change their own architecture, and they have structural building blocks that generate force and constantly come on and off. A description of such structures defies current traditional mechanical frameworks. It requires approaches that account for active force-generating parts and for the

formation of spatial and temporal patterns utilizing a diverse array of building blocks. In this Perspective, we term this framework “emergent mechanics.” Through examples at molecular, cellular, and tissue scales, we highlight challenges and opportunities in quantitatively understanding the emergent mechanics of biological structures and the need for new conceptual frameworks and experimental tools on the way ahead.”
“OBJECTIVE: To analyze serum biomarkers of CVD in selected patients with primary axial reflux of great saphenous vein in one or both lower limbs. PATIENTS AND METHODS: Ninety-six patients affected by uncomplicated varicose veins,

were enrolled in the study. A unilateral, primary axial reflux in great saphenous veins was detected in 54 patients (U-CVD group) and a bilateral one in 42 (B-CVD group). Sixty-five age and sex-matched subjects without venous reflux were enrolled as controls. Mean venous pressure of both lower limbs at the distal great saphenous vein (mGSVP) and venous reflux were measured by continuous-wave Doppler ultrasound and echoduplex scanning, respectively. selleck chemicals llc Reactive

Oxygen Species (ROS), tissue Plasminogen Activator (t-PA) and its Inhibitor 1 (PAI-1) activities, Hematocrit (HTC), White Blood Cells (WBC), Neutrophyls (NEU), Platelets (PLT), Fibrinogen (FIB) and Blood Viscosity (BV) were assessed in blood samples drawn A-1210477 from the antecubital vein. RESULTS: B-CVD group showed higher fibrinogen values (p smaller than 0.005) and higher mean venous pressure (0 smaller than 0.0001) in comparison to controls, while U-CVD did not. No difference was found between both groups and controls for all the other parameters. CONCLUSIONS: Increased fibrinogen levels in patients with bilateral varicose veins may represent an early warning signal, as it could be associated to the long-term progression of chronic venous disease.”
“Lieberthal W, Levine JS. Mammalian target of rapamycin and the kidney. II. Pathophysiology and therapeutic implications. Am J Physiol Renal Physiol 303: F180-F191, 2012. First published April 11, 2012; doi:10.1152/ajprenal.00015.2012.-The mTOR pathway plays an important role in a number of common renal diseases, including acute kidney injury (AKI), diabetic nephropathy (DN), and polycystic kidney diseases (PKD).

CONCLUSIONDietary supplementation with hardaliye affect the MDA, DC and homocysteine levels in blood, possibly due to the presence of antioxidant compounds. Dose response was only observed for homocysteine. Further studies need to be performed to assess the effects on antioxidant capacity. (c) 2013 Society of Chemical Industry”
“Endometriosis is a very common disease that is characterized by increased formation of estradiol and disturbed progesterone A-1210477 action. This latter is usually explained by a lack of progesterone receptor B (PR-B) expression, while the role of pre-receptor metabolism of progesterone is not yet fully understood. In normal endometrium, progesterone is metabolized by reductive 20 alpha-hydroxysteroid

dehydrogenases (20 alpha-HSDs), 3 alpha/beta-HSDs and 5 alpha/beta-reductases. The aldo-keto reductases 1C1 and 1C3 (AKR1C1 and AKR1C3) are the major reductive 20 alpha-HSDs, while the oxidative reaction is catalyzed by 17 beta-HSD type 2 (HSD17B2). Also, 3 alpha-HSD and 3 beta-HSD activities have been associated with the AKR1C isozymes. Additionally, 5 alpha-reductase types 1 and 2 (SRD5A1, SRD5A2) and 5 beta-reductase (AKR1D1) are responsible for the formation of 5 alpha- and 5 beta-reduced pregnanes. In this study, we examined the expression of PR-AB and the progesterone metabolizing enzymes in 31 specimens of ovarian endometriosis and 28 specimens of normal endometrium. Real-time PCR analysis revealed significantly decreased

mRNA check details levels of PR-AB, HSD17B2 and SRD5A2, significantly increased mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1, and negligible mRNA levels of AKR1D1. Immunohistochemistry staining of endometriotic tissue compared to control endometrium showed significantly lower PR-B levels in epithelial cells and no significant differences in stromal cells, there were no significant differences in the expression of AKR1C3 and significantly higher AKR1C2 levels were seen only in stromal cells. Our expression analysis data at the mRNA level and partially at the cellular level thus suggest enhanced metabolism of progesterone by SRD5A1 and the 20 alpha-HSD and 3 alpha/beta-HSD activities of

AKR1C1, AKR1C2 and AKR1C3. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Ehrlichia learn more chaffeensis is an obligate intracellular bacterium that causes human monocytic ehrlichiosis (HME). To determine what host components are important for bacterial replication, we performed microarray analysis on Drosophila melanogaster S2 cells by comparing host gene transcript levels between permissive and nonpermissive conditions for E. chaffeensis growth. Five-hundred twenty-seven genes had increased transcript levels unique to permissive growth conditions 24 h postinfection. We screened adult flies that were mutants for several of the “permissive” genes for the ability to support Ehrlichia replication. Three additional D. melanogaster fly lines with putative mutations in pyrimidine metabolism were also tested.

This study highlights the need to consider regional differences in climate, native vegetation, and the importance of macroinvertebrates, when assessing the effects of plantations on stream ecosystem processes such as carbon cycling. It also suggests that preservation of native riparian corridors, especially in drier areas, where the native vegetation provides high quality litter to the Selleck VX-689 streams, and where invertebrates play an important

role in aquatic processes, may mitigate the effects of plantations on stream communities and processes. (C) 2014 Elsevier B.V. All rights reserved.”
“Background. The standard of performing emergent surgical repair for acute aortic dissection type A has been questioned in patients with previous cardiac surgery. The effects of previous cardiac surgery on the presentation and operative outcome of these patients is understudied.\n\nMethods. Between 1998 and 2010, 190 patients were operated on for acute type A aortic

dissection; there were 159 first cardiac operations (FCO) and 31 redo operations (REDO). Stepwise logistic regression analysis identified independent predictors of hospital mortality. Propensity Fer-1 score-matching yielded 31 FCOs who matched the REDOs with respect to age, sex, hypertension history, chronic obstructive pulmonary disease, and renal failure. The presentation, operative outcome, and complications were compared between the two groups.\n\nResults. ALK inhibitor Hospital mortality rate was 16.8% (32 of 190). Regression analysis identified mental status change (odds ratio [OR] = 5.9), hypertension (OR = 4.6), concomitant coronary artery bypass grafting (OR = 3), reoperation (OR = 2.9), and age

of 70 years or older (OR = 2.8) as predictors of hospital mortality. After matching there was no difference between REDO and FCO groups in the presenting symptoms, but REDOs had a higher incidence of aortic rupture (29% [9 of 31] versus 3.2% [1 of 31]; p = 0.012). Cardiac tamponade was present in 3.2% (1 of 31) of REDOs versus 16.1% of FCOs (5 of 31; p = 0.195). Patients in the REDO group required more intraoperative blood transfusion, and had longer cardiopulmonary bypass time. Major complications occurred similarly between the two groups, except REDOs had worse renal function and a higher rate of sudden cardiac arrest (14.3% [4 of 28] versus 0; p = 0.045).\n\nConclusions. Although hospital mortality is higher among REDOs, it is still lower than the reported mortality for medical management, and major complications occurred at a rate similar to that of FCOs; hence, emergent surgery remains the prudent treatment. (Ann Thorac Surg 2012;93:1206-14) (C) 2012 by The Society of Thoracic Surgeons”
“The oxygenation of polyunsaturated fatty acids by lipoxygenases (LOX) is associated with a lag phase during which the resting ferrous enzyme is converted to the active ferric form by reaction with fatty acid hydroperoxide.

This case is very rare, because most cases of pancreatic metastasis from lung cancer

have already widespread disease at the time of diagnosis. This case illustrates that pancreatic metastasis from SCH727965 supplier pulmonary adenocarcinoma should be borne in mind, even if the pancreatic tumor is a solitary lesion without additional organ metastasis.”
“Objective: This study was conducted to explore the association between sexual orientations and poly-cystic ovary syndrome (PCOS)-related parameters. Materials and methods: A cross-sectional study with participants recruited from the regular outpatient clinic at the Department of Obstetrics and Gynecology at Taipei Medical University Hospital, Taipei, Taiwan between July 2012 and December 2013 was carried this website out. A total of 97 women met the criterion of having been diagnosed with PCOS. Among these 97 women, 89 were heterosexuals and eight were self-identified as lesbians. At the same time, 78 women without PCOS were enrolled to serve as the control group. Participants were given a standard questionnaire and had blood withdrawn for biochemical analysis of androgen parameters-including total testosterone, androstenedione, sex hormone binding globulin, free androgen

index, 17 beta-estradiol (E2), luteinizing hormone, and follicular-stimulating hormone. The biochemical data were measured to compare the PCOS clinical parameters Z-IETD-FMK chemical structure present in people of different sexual orientations (lesbians and heterosexuals). Results: The women with PCOS, regardless of sexual orientation, had higher percentages and serum levels of hyperandrogenism-related clinical parameters than the women without PCOS [acne (87.5% and 60.7% vs. 23.1%), p smaller than 0.001]; hirsutism (62.5% and 57.3% vs. 15.4%, p smaller than = 0.001)]; and biochemical parameters (total

T. p smaller than 0.05 or p smaller than 0.001, and luteinizing hormone/follicular-stimulating hormone ratio, p smaller than = 0.001). The sexual orientation of women with PCOS affected their body mass index (BMI), because lesbians with PCOS possessed higher BMI than heterosexual women with PCOS (26.5 +/- 1.9 vs. 22.5 +/- 0.55; p smaller than 0.05). However, hyperandrogenism-related clinical and biochemical parameters were not significantly different statistically between women with PCOS but of different sexual orientations. Conclusion: Our preliminary data showed that sexual orientation influenced the BMI of women with PCOS, but did not affect hyperandrogenism-related clinical or biochemical characteristics. This observation requires further confirmation. Copyright (C) 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.”
“Rationale: The nonspecific clinical presentation of pulmonary embolism (PE) frequently leads to delay in its diagnosis.

During a median follow-up of 46 months, 13 patients (17 %) reached the composite end point. At baseline, patients with and without events showed comparable values of LV longitudinal strain at the infarct, border, and remote zones. However, at three months’ follow-up, patients with events showed significantly more impaired longitudinal strain at the border zone (-6.8 +/- 3.1 % vs. -10.5 +/- 4.9 %, P = 0.002), whereas LVEF was comparable (28 +/- 6 % vs. 31 +/- 4 %, P = 0.09). The median three-month LV longitudinal strain at the border zone was -9.4 %. Multivariate Cox regression analysis demonstrated

that three-month longitudinal strain bigger than -9.4 % at the border zone was independently associated with the composite end point (hazard ratio 3.94, 95 % confidence interval 1.05-14.70; P = 0.04). In conclusion, regional longitudinal strain at the border zone three months post-STEMI is associated with SBE-β-CD mw appropriate ICD Nutlin-3a manufacturer therapy and cardiac mortality.”
“Zager

RA, Vijayan A, Johnson AC. Proximal tubule haptoglobin gene activation is an integral component of the acute kidney injury “stress response”. Am J Physiol Renal Physiol 303: F139-F148, 2012. First published May 9, 2012; doi:10.1152/ajprenal. 00168.2012.-Haptoglobin (Hp) synthesis occurs almost exclusively in liver, and it is rapidly upregulated in response to stress. Because many of the pathways that initiate hepatic Hp synthesis are also operative during acute kidney injury (AKI), we tested whether AKI activates the renal cortical Hp gene. CD-1 mice were subjected to six diverse AKI models: ischemia-reperfusion, glycerol injection, cisplatin nephrotoxicity, myoglobinuria, endotoxemia, and Stem Cell Compound Library chemical structure bilateral ureteral obstruction. Renal cortical Hp gene

induction was determined either 4-72 h or 1-3 wk later by measuring Hp mRNA and protein levels. Relative renal vs. hepatic Hp gene induction during endotoxemia was also assessed. Each form of AKI induced striking and sustained Hp mRNA increases, leading to similar to 10- to 100-fold renal Hp protein elevations (ELISA; Western blot). Immunohistochemistry, and isolated proximal tubule assessments, indicated that the proximal tubule was the dominant (if not only) site of the renal Hp increases. Corresponding urinary and plasma Hp elevations were surrogate markers of this response. Endotoxemia evoked 25-fold greater Hp mRNA increases in kidney vs. liver, indicating marked renal Hp gene reactivity. Clinical relevance of these findings was suggested by observations that urine samples from 16 patients with established AKI had statistically higher (similar to 12x) urinary Hp levels than urine samples from either normal subjects or from 15 patients with chronic kidney disease. These AKI-associated urinary Hp increases mirrored those seen for urinary neutrophil gelatinase-associated lipoprotein, a well accepted AKI biomarker gene.