Heterotopic Pancreas: Unusual Cause of Usual Diarrhoea.

Heterotopic pancreas (HP) also known as ectopic pancreas, pancreatic crest or accessory pancreas is the normal pancreatic tissue, found in a remote area other than its natural location, with no anatomic or vascular connection to main pancreatic tissue. It is a rare congenital anomaly and has been reported at many locations such as stomach (antrum) and small intestine. HP is usually an incidental finding and asymptomatic, however there are reports of pancreatitis, obstruction, perforation and malignant transformation as uncommon manifestations. Diagnosis of HP is primarily based on histological examination either by biopsy or surgical excision. Surgery is the standard treatment for symptomatic HP patients. Herein, we present a case of a 58-year-old female, who presented to us with intractable diarrhoea due to HP in the jejunum and underwent minimally invasive surgery for definitive diagnosis and treatment.

Application of a protein domain as chaperone for enhancing biological activity and stability of other proteins.

Chaperones are a diverse class of molecules known for increasing thermo-stability of proteins, preventing protein aggregation, favoring disaggregation, increasing solubility and in some cases imparting resistance to proteolysis. These functions can be employed for various biotechnological applications including point of care testing, nano-biotechnology, bio-process engineering, purification technologies and formulation development. Here we report that the N-terminal domain of Pyrococcus furiosusl-asparaginase, (NPfA, a protein chaperone lacking α-crystallin domain) can serve as an efficient, industrially relevant, protein additive. We tested the effect of NPfA on substrate proteins, ascorbate peroxidase (APX), IgG peroxidase antibodies (I-HAbs) and KOD DNA polymerase. Each protein not only displayed increased thermal stability but also increased activity in the presence of NPfA. This increase was either comparable or higher than those obtained by common osmolytes; glycine betaine, sorbitol and trehalose. Most dramatic activity enhancement was seen in the case of KOD polymerase (∼ 40 % increase). NPfA exerts its effect through transient binding to the substrate proteins as discerned through isothermal titration calorimetry, dynamic light scattering and size exclusion chromatography. Mechanistic insights obtained through simulations suggested a remodeled architecture and emergence of H-binding network between NPfA and substrate protein with an effective enhancement in the solvent accessibility at the active site pocket of the latter. Thus, the capability of NPfA to engage in specific manner with other proteins is demonstrated to reduce the concentration of substrate proteins/enzymes required per unit operation. The functional expansion obtained through our finding establishes NPfA as a novel class of ATP-independent molecular chaperone with immense future biotechnological applications.

Critical amino acid variations in HLA-DQB1* molecules confers susceptibility to Autoimmune Thyroid Disease in south India.

The HLA-DQB1* region exhibits complex associations with autoimmune thyroid disease (AITD). AITD patients (Hashimoto's thyroiditis, HT = 180; Graves' disease, GD = 55) and age/sex matched controls (n = 235) were genotyped for DQB1* alleles by PCR-SSP. Alleles DQB1*02:02, *06:03, *06:09, *03:02, and *03:03 showed an increased risk and *02:01, *05:02, and *06:02 showed a protection toward AITD. Multiple sequence alignment was used to find out the amino acid variations within the peptide-binding pockets of susceptible and/or protective DQB1* alleles. We observed susceptible associations for amino acids 'Glu86(P < 0.0007)' and 'Leu87(P < 3.8 × 10-4)' in P1, 'Leu26(P < 4.0 × 10-12)' in P4, 'His9(P < 5.0 × 10-4)' and 'Ala57(P < 3.6 × 10-4)' in P9 toward HT; and 'Gly86(P < 0.0004)' in P1 and 'Asp57(P < 1.9 × 10-4)' in P9 towards GD. Protective associations were observed for amino acids 'Ala86(P < 8.2 × 10-6)' and 'Tyr87(P < 0.0003)' in P1, 'Gly26(P < 4.9 × 10-5)' and 'Ser74(P < 4.9 × 10-5)' in P4, 'Phe9(P < 0.0007)' and 'Ser57(P < 0.0016)' in P9 towards HT. Thus, the present study revealed that DQB1* alleles and putative amino acid residues play an important role in susceptibility toward AITD in south India.

STAT3 antisense oligonucleotide AZD9150 in a subset of patients with heavily pretreated lymphoma: results of a phase 1b trial.

BACKGROUND: The Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in both tumorigenesis and activation of immune responses. In diffuse large B-cell lymphoma (DLBCL), the transcription factor STAT3 has been associated with aggressive disease phenotype and worse overall survival. While multiple therapies inhibit upstream signaling, there has been limited success in selectively targeting STAT3 in patients. Antisense oligonucleotides (ASOs) represent a compelling therapeutic approach to target difficult to drug proteins such as STAT3 through of mRNA targeting. We report the evaluation of a next generation STAT3 ASO (AZD9150) in a non-Hodgkin's lymphoma population, primarily consisting of patients with DLBCL. METHODS: Patients with relapsed or treatment refractory lymphoma were enrolled in this expansion cohort. AZD9150 was administered at 2 mg/kg and the 3 mg/kg (MTD determined by escalation cohort) dose levels with initial loading doses in the first week on days 1, 3, and 5 followed by weekly dosing. Patients were eligible to remain on therapy until unacceptable toxicity or progression. Blood was collected pre- and post-treatment for analysis of peripheral immune cells. RESULTS: Thirty patients were enrolled, 10 at 2 mg/kg and 20 at 3 mg/kg dose levels. Twenty-seven patients had DLBCL. AZD9150 was safe and well tolerated at both doses. Common drug-related adverse events included transaminitis, fatigue, and thrombocytopenia. The 3 mg/kg dose level is the recommended phase 2 dose. All responses were seen among DLBCL patients, including 2 complete responses with median duration of response 10.7 months and 2 partial responses. Peripheral blood cell analysis of three patients without a clinical response to therapy revealed a relative increase in proportion of macrophages, CD4+, and CD8+ T cells; this trend did not reach statistical significance. CONCLUSIONS: AZD9150 was well tolerated and demonstrated efficacy in a subset of heavily pretreated patients with DLBCL. Studies in combination with checkpoint immunotherapies are ongoing. TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT01563302 . First submitted 2/13/2012.

Automated statistical experimental design approach for rapid separation of coenzyme Q10 and identification of its biotechnological process related impurities using UHPLC and UHPLC-APCI-MS.

A novel ultra high performance liquid chromatography method development strategy was ameliorated by applying quality by design approach. The developed systematic approach was divided into five steps (i) Analytical Target Profile, (ii) Critical Quality Attributes, (iii) Risk Assessments of Critical parameters using design of experiments (screening and optimization phases), (iv) Generation of design space, and (v) Process Capability Analysis (Cp) for robustness study using Monte Carlo simulation. The complete quality-by-design-based method development was made automated and expedited by employing sub-2 µm particles column with an ultra high performance liquid chromatography system. Successful chromatographic separation of the Coenzyme Q10 from its biotechnological process related impurities was achieved on a Waters Acquity phenyl hexyl (100 mm × 2.1 mm, 1.7 µm) column with gradient elution of 10 mM ammonium acetate buffer (pH 4.0) and a mixture of acetonitrile/2-propanol (1:1) as the mobile phase. Through this study, fast and organized method development workflow was developed and robustness of the method was also demonstrated. The method was validated for specificity, linearity, accuracy, precision, and robustness in compliance to the International Conference on Harmonization, Q2 (R1) guidelines. The impurities were identified by atmospheric pressure chemical ionization-mass spectrometry technique. Further, the in silico toxicity of impurities was analyzed using TOPKAT and DEREK software.

Susceptible and protective associations of HLA DRB1*/DQB1* alleles and haplotypes with ischaemic stroke.

Stroke has emerged as the second commonest cause of mortality worldwide and is a major public health problem. For the first time, we present here the association of human leucocyte antigen (HLA)-DRB1*/DQB1* alleles and haplotypes with ischaemic stroke in South Indian patients. Ischaemic stroke (IS) cases and controls were genotyped for HLA-DRB1*/DQB1* alleles by polymerase chain reaction sequence-specific primers (PCR-SSP) method. The frequencies of HLA class II alleles such as DRB1*04, DRB1*07, DRB1*11, DRB1*12, DRB1*13, DQB1*02 and DQB1*07 were high in IS patients than in the age- and gender-matched controls, suggesting that the individuals with these alleles are susceptible to ischaemic stroke in South India. The frequencies of alleles such as DRB1*03, DRB1*10, DRB1*14, DQB1*04 and DQB1*05 were less in IS cases than in the controls, suggesting a protective association. Haplotypes DRB1*04-DQB1*0301, DRB1*07-DQB1*02, DRB1*07-DQB1*0301, DRB1*11-DQB1*0301 and DRB1*13-DQB1*06 were found to be high in IS patients conferring susceptibility. The frequency of haplotype DRB1*10-DQB1*05 was high in controls conferring protection. IS-LVD and gender-stratified analysis too confirmed these susceptible and protective associations. Thus, HLA-DRB1*/DQB1* alleles and haplotypes strongly predispose South Indian population to ischaemic stroke. Further studies in different populations with large sample size or the meta-analysis are needed to explain the exact mechanism of associations of HLA gene(s) with IS.

The TGF-ß/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia.

Natural killer (NK) cells are key components of the innate immune system, providing potent antitumor immunity. Here, we show that the tumor growth factor-ß (TGF-ß)/SMAD signaling pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia (ALL). We characterized NK cells in 50 consecutive children with B-ALL at diagnosis, end induction and during maintenance therapy compared with age-matched controls. ALL-NK cells at diagnosis had an inhibitory phenotype associated with impaired function, most notably interferon-γ production and cytotoxicity. By maintenance therapy, these phenotypic and functional abnormalities partially normalized; however, cytotoxicity against autologous blasts remained impaired. We identified ALL-derived TGF-ß1 to be an important mediator of leukemia-induced NK cell dysfunction. The TGF-ß/SMAD signaling pathway was constitutively activated in ALL-NK cells at diagnosis and end induction when compared with healthy controls and patients during maintenance therapy. Culture of ALL blasts with healthy NK cells induced NK dysfunction and an inhibitory phenotype, mediated by activation of the TGF-ß/SMAD signaling pathway, and abrogated by blocking TGF-ß. These data indicate that by regulating the TGF-ß/SMAD pathway, ALL blasts induce changes in NK cells to evade innate immune surveillance, thus highlighting the importance of developing novel therapies to target this inhibitory pathway and restore antileukemic cytotoxicity.

AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer.

Next-generation sequencing technologies have greatly expanded our understanding of cancer genetics. Antisense technology is an attractive platform with the potential to translate these advances into improved cancer therapeutics, because antisense oligonucleotide (ASO) inhibitors can be designed on the basis of gene sequence information alone. Recent human clinical data have demonstrated the potent activity of systemically administered ASOs targeted to genes expressed in the liver. We describe the preclinical activity and initial clinical evaluation of a class of ASOs containing constrained ethyl modifications for targeting the gene encoding the transcription factor STAT3, a notoriously difficult protein to inhibit therapeutically. Systemic delivery of the unformulated ASO, AZD9150, decreased STAT3 expression in a broad range of preclinical cancer models and showed antitumor activity in lymphoma and lung cancer models. AZD9150 preclinical activity translated into single-agent antitumor activity in patients with highly treatment-refractory lymphoma and non-small cell lung cancer in a phase 1 dose-escalation study.

Technical considerations in brachytherapy boost for a case of squamous cell carcinoma of the external auditory canal based on our case.

Squamous cell carcinoma of the external auditory canal is a rare entity. The patients present with ear discharge and otalgia. They are treated with radiotherapy and surgery. Surgery with oncological priorities is quite complex with substantial consequences. We are reporting a patient with squamous cell carcinoma of the external auditory canal, who was treated with limited surgery followed by radiotherapy. Radiotherapy was a combination of external beam radiotherapy and brachytherapy. High dose rate brachytherapy was given using an ear speculum fixed with wax and a suction catheter. This article is to highlight the technique and dosimetry of the brachytherapy procedure.

Selective separation and characterization of the stress degradation products of ondansetron hydrochloride by liquid chromatography with quadrupole time-of-flight mass spectrometry.

Ondansetron hydrochloride was subjected to forced degradation studies under various conditions of hydrolysis (acidic, basic, and neutral), oxidation, photolysis, and thermal as prescribed by International Conference on Harmonisation guideline Q1A (R2). A simple, selective, precise, and accurate high-performance liquid chromatography method was developed on a Waters Xterra C18 (150 × 4.6 mm id, 3.5 µm) column using 10 mM ammonium formate (pH 3.0)/methanol as a mobile phase in gradient elution mode at a flow rate of 0.6 mL/min. The method was extended to liquid chromatography quadrupole time-of-flight tandem mass spectrometry for identification and structural characterization of stress degradation products of ondansetron. The drug showed significant degradation in base hydrolytic and photolytic stress conditions in the liquid state, while it was found to be stable in neutral, acidic, thermal, and oxidative stress conditions. A total of five degradation products were characterized and most probable mechanisms for the formation of degradation products have been proposed on the basis of a comparison of the fragmentation of the [M + H](+) ions of the drug and its degradation products. Finally, the developed method was validated in terms of specificity, linearity, accuracy, precision, and robustness as per International Conference on Harmonisation guideline Q2 (R1).

Quality by design: a systematic and rapid liquid chromatography and mass spectrometry method for eprosartan mesylate and its related impurities using a superficially porous particle column.

The present work describes the systematic development of a robust, precise, and rapid reversed-phase liquid chromatography method for the simultaneous determination of eprosartan mesylate and its six impurities using quality-by-design principles. The method was developed in two phases, screening and optimization. During the screening phase, the most suitable stationary phase, organic modifier, and pH were identified. The optimization was performed for secondary influential parameters--column temperature, gradient time, and flow rate using eight experiments--to examine multifactorial effects of parameters on the critical resolution and generated design space representing the robust region. A verification experiment was performed within the working design space and the model was found to be accurate. This study also describes other operating features of the column packed with superficially porous particles that allow very fast separations at pressures available in most liquid chromatography instruments. Successful chromatographic separation was achieved in less than 7 min using a fused-core C18 (100 mm × 2.1 mm, 2.6 µm) column with linear gradient elution of 10 mM ammonium formate (pH 3.0) and acetonitrile as the mobile phase. The method was validated for specificity, linearity, accuracy, precision, and robustness in compliance with the International Conference on Harmonization Q2 (R1) guidelines. The impurities were identified by liquid chromatography with mass spectrometry.

ROLE OF MICROPERC IN MINIMAL INVASIVE EXTRACTION OF Renal STONES IN CHILDREN.

BACKGROUND: Microperc using all-seeing needle is associated with reduced tract-related morbidity. AIM & OBJECTIVES: The purpose of this study was to examine the effectiveness and safety of microperc in children. PATIENTS & METHODS: From July 2010 to August 2014, a total of 17 children with renal stones underwent microperc at Muljibhai Patel Urological Hospital, Nadiad, India. Renal access was achieved through 4.85-Fr (16 gauge) all-seeing needle (PolyDiagnost, Pfaffenhofen, Germany). and fragmentation with 200 µm holmium:YAG laser fiber. The patient's demographic data, clinical features, operating time, hemoglobin drop, stone clearance, complications (Clavien-Dindo), and length of hospital stay were prospectively studied. RESULTS: A total of 17 patients with a median age of 9 years were studied. The stone size ranged from 5.3mm to 24.9mm. The median operative time was 40 minutes. The median decrease in haemoglobin was 1.2 mg/dl. The stone-free rate at first postoperative day and at the first month after the procedure were 82.4% and 88.2% respectively. The mean hospital stay was 56.4 hours. None of the patients required blood transfusion. An overall success rate of 94.1% was achieved at median follow-up of 4 months. Comparing small size stones (< 1cm) and moderate size stone (1-3cm); the immediate clearance rates were 100% and 75% respectively (p=0.331). There was no statistically significant difference in the operating time (40 vs 43mins; p=0.592), haemoglobin drop (0.85 vs 1.25 g/dl; p=0.595) and the length of hospital stay. One patient in each group had conversion to miniperc to remove residual stone fragment. There was one minor intra-operative pelvic perforation (Clavien II). There were two postoperative complications in patients with moderate stone; one of the patients had right lower lobar pneumonia and the other had colic pain and both cases were managed conservatively (Clavien I). CONCLUSION: This study has demonstrated that microperc is a safe and effective procedure in the extraction of small to medium size renal stones in children.

Adenovirus death protein (ADP) is required for lytic infection of human lymphocytes.

The adenovirus death protein (ADP) is expressed at late times during a lytic infection of species C adenoviruses. ADP promotes the release of progeny virus by accelerating the lysis and death of the host cell. Since some human lymphocytes survive while maintaining a persistent infection with species C adenovirus, we compared ADP expression in these cells with ADP expression in lymphocytes that proceed with a lytic infection. Levels of ADP were low in KE37 and BJAB cells, which support a persistent infection. In contrast, levels of ADP mRNA and protein were higher in Jurkat cells, which proceed with a lytic infection. Epithelial cells infected with an ADP-overexpressing virus died more quickly than epithelial cells infected with an ADP-deleted virus. However, KE37, and BJAB cells remained viable after infection with the ADP-overexpressing virus. Although the levels of ADP mRNA increased in KE37 and BJAB cells infected with the ADP-overexpressing virus, the fraction of cells with detectable ADP was unchanged, suggesting that the control of ADP expression differs between epithelial and lymphocytic cells. When infected with an ADP-deleted adenovirus, Jurkat cells survived and maintained viral DNA for greater than 1 month. These findings are consistent with the notion that the level of ADP expression determines whether lymphocytic cells proceed with a lytic or a persistent adenovirus infection.

Comparative analysis between 5 mm and 7.5 mm collimators in CyberKnife radiosurgery for trigeminal neuralgia.

Trigeminal neuralgia (TN) is treated in CyberKnife (Accuray Inc, Sunnyvale, USA) with the 5 mm collimator whose dosimetric inaccuracy is higher than the other available collimators. The 7.5 mm collimator which is having less dosimetric uncertainty can be an alternative for 5 mm collimator provided the dose distribution with 7.5 mm collimator is acceptable. Aim of this study is to analyze the role of 7.5 mm collimator in CyberKnife treatment plans of TN. The treatment plans with 5 mm collimators were re-optimized with 7.5 mm collimator and a bi-collimator system (5 mm and 7.5 mm). The treatment plans were compared for target coverage, brainstem doses, and the dose to normal tissues. The target and brainstem doses were comparable. However, the conformity indices were 2.31 ± 0.52, 2.40 ± 0.87 and 2.82 ± 0.51 for 5 mm, bi-collimator (5mm and 7.5 mm), 7.5 mm collimator plans respectively. This shows the level of dose spillage in 7.5 mm collimator plans. The 6 Gy dose volumes in 7.5 mm plans were 1.53 and 1.34 times higher than the 5 mm plan and the bi-collimator plans respectively. The treatment time parameters were lesser for 7.5 mm collimators. Since, the normal tissue dose is pretty high in 7.5 mm collimator plans, the use of it in TN plans can be ruled out though the treatment time is lesser for these 7.5 mm collimator plans.

A study on rectal dose measurement in phantom and in vivo using Gafchromic EBT3 film in IMRT and CyberKnife treatments of carcinoma of prostate.

The objective of this study is to check the feasibility of in vivo rectal dose measurement in intensity-modulated radiotherapy (IMRT) and CyberKnife treatments for carcinoma prostate. An in-house pelvis phantom made with bee's wax was used in this study. Two cylindrical bone equivalent materials were used to simulate the femur. Target and other critical structures associated with carcinoma prostate were delineated on the treatment planning images by the radiation oncologist. IMRT treatment plan was generated in Oncentra Master Plan treatment planning system and CyberKnife treatment plan was generated in Multiplan treatment planning system. Dose measurements were carried out in phantom and in patient using Gafchromic EBT3 films. RIT software was used to analyze the dose measured by EBT3 films. The measured doses using EBT3 films were compared with the TPS-calculated dose along the anterior rectal wall at multiple points. From the in-phantom measurements, it is observed that the difference between calculated and measured dose was mostly within 5%, except for a few measurement points. The difference between calculated and measured dose in the in-patient measurements was higher than 5% in regions which were away from the target. Gafchromic EBT3 film is a suitable detector for in vivo rectal dose measurements as it offers the possibility of analyzing the dose at multiple points. In addition, the method of extending this in vivo rectal dose measurement technique as a tool for patient-specific quality assurance check is also analyzed.

Analysis of high-dose rate brachytherapy dose distribution resemblance in CyberKnife hypofractionated treatment plans of localized prostate cancer.

The present study is to analyze the CyberKnife hypofractionated dose distribution of localized prostate cancer in terms of high-dose rate (HDR) brachytherapy equivalent doses to assess the degree of HDR brachytherapy resemblance of CyberKnife dose distribution. Thirteen randomly selected localized prostate cancer cases treated using CyberKnife with a dose regimen of 36.25Gy in 5 fractions were considered. HDR equivalent doses were calculated for 30Gy in 3 fractions of HDR brachytherapy regimen. The D5% of the target in the CyberKnife hypofractionation was 41.57 ± 2.41Gy. The corresponding HDR fractionation (3 fractions) equivalent dose was 32.81 ± 1.86Gy. The mean HDR fractionation equivalent dose, D98%, was 27.93 ± 0.84Gy. The V100% of the prostate target was 95.57% ± 3.47%. The V100% of the bladder and the rectum were 717.16 and 79.6mm(3), respectively. Analysis of the HDR equivalent dose of CyberKnife dose distribution indicates a comparable resemblance to HDR dose distribution in the peripheral target doses (D98% to D80%) reported in the literature. However, there is a substantial difference observed in the core high-dose regions especially in D10% and D5%. The dose fall-off within the OAR is also superior in reported HDR dose distribution than the HDR equivalent doses of CyberKnife.

Evaluation of integrated anaerobic-aerobic biofilm reactor for degradation of azo dye methyl orange.

This study was to investigate the mineralization of wastewater containing methyl orange (MO) in integrated anaerobic-aerobic biofilm reactor with coconut fiber as bio-material. Different aeration periods (3h in phase 1 and 2; 3, 6 and 15 h in phase 3; 24 h in phase 4 and 5) in aerobic chamber were studied with different MO concentration 50, 100, 200, 200 and 300 mg/L as influent from phase 1-5. The color removals estimated from the standard curve of dye versus optical density at its maximum absorption wavelength were 97%, 96%, 97%, 97%, and 96% and COD removals were 75%, 72%, 63%, 81%, and 73% in phase 1-5, respectively. The MO decolorization and COD degradation followed first-order kinetic model and second-order kinetic model, respectively. GC-MS analysis indicated the symmetrical cleavage of azo bond and the reduction in aromatic peak ensured the partial mineralization of MO.

Comprehensive review and compilation of treatment for azo dyes using microbial fuel cells.

Microbial fuel cells (MFCs) represent an emerging technology that focuses on power generation and effluent treatment. This review compiles articles related to MFCs using azo dye as the substrate. The significance of the general components in MFCs and systems of MFCs treating azo dye is depicted in this review. In addition, degradation of azo dyes such as Congo red, methyl orange, active brilliant red X-3B, amaranth, reactive blue 221, and acid orange 7 in MFCs are summarized. Further exploration and operational modification are suggested to address the challenges of complete removal of azo dye with maximum power generation in an MFC. In addition, a sequential treatment system with MFCs is suggested for complete mineralization of azo dye.

Renal biomarker changes associated with hyaline droplet nephropathy in rats are time and potentially compound dependent.

Alpha 2u-globulin mediated hyaline droplet nephropathy (HDN) is a male rat specific lesion induced when a compound or metabolite binds to alpha 2u-globulin. The objective of this study was to investigate if the newer and more sensitive renal biomarkers would be altered with HDN as well as be able to distinguish between HDN and oxidative stress-induced kidney injury. Rats were dosed orally for 7 days to determine (1) if HDN (induced by 2-propanol or D-limonene) altered the newer renal biomarkers and not BUN or creatinine, (2) if renal biomarkers could distinguish between HDN and oxidative stress-induced kidney injury (induced by potassium bromate), (3) sensitivity of HDN-induced renal biomarker changes relative to D-limonene dose, and (4) reversibility of HDN and renal biomarkers, using vehicle or 300 mg/kg/day D-limonene with 7 days of dosing and necropsies scheduled over the period of Days 8-85. HDN-induced renal biomarker changes in male rats were potentially compound specific: (1) 2-propanol induced mild HDN without increased renal biomarkers, (2) potassium bromate induced moderate HDN with increased clusterin, and (3) D-limonene induced marked HDN with increased αGST, µGST and albumin. Administration of potassium bromate did not result in oxidative stress-induced kidney injury, based on histopathology and renal biomarkers creatinine and BUN. The compound D-limonene induced a dose dependent increase in HDN severity and renal biomarker changes without altering BUN, creatinine or NAG: (1) minimal induction of HDN and no altered biomarkers at 10 mg/kg/day, (2) mild induction of HDN with increased αGST and µGST at 50 mg/kg/day and (3) marked induction of HDN with increased αGST, µGST and albumin at 300 mg/kg/day. HDN induced by D-limonene was reversible, but with a variable renal biomarker pattern over time: Day 8 there was increased αGST, µGST and albumin; on Day 15 increased clusterin, albumin and Kim-1. In summary, HDN altered the newer and more sensitive renal biomarkers in a time and possibly compound dependent manner.