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PubMed1983

Skin ulceration potential without therapeutic anticancer activity for epipodophyllotoxin commercial diluents.

The epipodophyllotoxin derivatives, etoposide (VP-16) and teniposide (VM-26), are highly lipophilic anticancer drugs supplied with novel commercial solvent systems. A BALB/c mouse skin toxicity model was used to evaluate the ulcerative potential of intradermal (ID) VP-16 and its lipophilic solvent system along with the main ingredient of the VM-26 solvent, polyethoxylated castor oil (PECO). ID VP-16 caused dose-dependent ulceration following 0.17 mg, 0.33 mg (50 mg/M2) or 1.0 mg (150 mg/M2). Both normal saline (0.05 ml ID) and hyaluronidase (7.5 u ID) were effective as local VP-16 antidotes, presumably by diluting out the extravasated drug. The VP-16 solvent alone was as toxic as the 1.0 mg (undiluted) ID VP-16 injection. ID PECO was mildly ulcerative in mouse skin. When given to P-388 lymphocytic leukemia-bearing mice, both VP-16 (24 mg/kg IP for 3 doses) and VM-26 (8 mg/kg IP for 2 doses) were active, producing increased life spans (ILS) of 160% and 90%, respectively. The solvents, given IP at the same schedule, did not increase or decrease the life span of tumor-bearing mice, but did increase morbidity. In an in vitro human tumor clonogenic assay (WiDr colon carcinoma and HEC-1A endometrial carcinoma in soft agar), both VP-16 and VM-26 showed moderate to complete inhibition of tumor colony forming units (TCFUs) by continuous exposure. 1-h drug exposures were marginally active at reducing TCFUs. None of the epipodophyllotoxin diluents at clinical concentrations reduced TCFUs. At very high concentrations, both epipodophyllotoxins were cytotoxic. They were more effective at reducing TCFUs when plated as a continuous exposure rather than a 1-h exposure.

Adenocarcinoma↗
PubMed1990

A respiratory tract dosimetry model for air toxics.

The development of a physiologically based pharmacokinetic model for the whole body in which inhalation, exhalation, and metabolism in respiratory tract tissues are taken into account is described. As an example of the model's use, the results of several experiments in which rats and humans were exposed to styrene were simulated; these results are discussed. The predicted results agree with the empirical data and with the modeling results of others.

Air Pollutants↗
PubMed2005

Functional recovery of glycine receptors in spastic murine model of startle disease.

Clinical variability is common in inherited gene defects of the central nervous system in humans and in animal models of human disorders. Here, we used the homozygous spastic (spa) mutant mice, which resemble human hereditary hyperekplexia, to determine the molecular remodeling of the spinal cord through the course of the disease, and develop a model for clinical disparity between littermates. The spa mutation is an insertion of a LINE-1 element in the gene for the beta subunit of the glycine receptor, Glrb. The insertion causes aberrant splicing in the beta subunit of glycine receptor gene with a consequent important reduction of glycine receptors. At young ages, all homozygous spa animals were spastic, showed loss of glycine receptors, increased expression of vesicular glycine/GABA transporter and NMDA receptors, induction of activated caspase3, and preferential loss of glycinergic interneurons consistent with neurotransmitter toxicity model. Those littermates that recovered from symptoms showed strong over-expression of the glycine receptor alpha 1 subunit (Glra1), and increased myelination and synaptic plasticity. Littermates that showed a deteriorating clinical course failed to over-express Glra1, and also showed relative loss of gephyrin (receptor clustering). These molecular changes were associated with a preferential loss of GABAergic interneurons, and extensive motorneuron loss. These data suggest that functional recovery is likely due to expression of homomeric glycine receptors, rescue from excitotoxicity, and subsequent neuronal remodeling. We propose that human patients with hyperekplexia show remodeling similar to that of the recovering spa mice, as human patients also show a lessening of symptoms as a function of age.

Animals↗
PubMedDate not supplied

Repeated immunolesions display diminished stress response signal.

Cholinergic basal forebrain neurons (CBFNs) retrogradely transport neurotrophins released in the hippocampus and cortex as part of a general response to injury in a process that is impaired in the aged rodent and can be spared by the exogenous addition of pharmacological doses of nerve growth factor (NGF). This observation suggests that components of stress response signal transduction pathways in the aged CNS can be exogenously activated. The extent and mechanism of the endogenous stimulation of NGF in response to injury can be mimicked via treatment with 192 IgG-saporin of rat CNS, an immunolesion model. Here we report on the use of a conditioning lesion paradigm to determine if repeated partial immunolesions have a conditioning effect on the immunolesion-induced increases in NGF protein or decreases in choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity. We report that chronic repeated immunolesions, as used here, were not as effective as a one time equivalent immunolesion in terms of induced NGF protein increases or decreasing ChAT and AChE activity in the hippocampus and cortex. Thus, chronic lesions resulting in cholinergic impairment typical of the aged CNS may differ from acute toxic models as a result of desensitization due to a conditioning effect of chronic subthreshold lesioning events in the CNS.

Acetylcholinesterase↗
PubMed2005

[Study on ultra-structural pathological changes of rats poisoned by tetramine].

OBJECTIVE: To observe ultra-structural pathological changes of materiality viscera of rats poisoned by different dose of tetramine and to study the toxic mechanism. METHODS: Acute and subacute tetramine toxicity models were made by oral administration with different dose of tetramine. Brain, heart, liver, spleen and kidney were extracted and observed by electromicroscopic examination. RESULTS: The injuries of brain cells, cardiocytes and liver cells were induced by different dose of tetramine. These were not obviously different of the injuries of the kindy cells and spleen cells of rats poisoned by different dose of tetramine. Ultra-structural pathological changes were abserved including mitochondria slight swelling and neurolemma's array turbulence in the brain cells, mitochondria swelling or abolish and rupture of muscle fiber in the heart cells, mitochondria swelling and the glycogen decreased in the liver cells. CONCLUSION: The toxic target organs of tetramine are the heart, brain and liver.

Animals↗
PubMed1997

Randomized comparison of total androgen blockade alone versus combined with weekly epirubicin in advanced prostate cancer.

Hormone deprivation is the gold standard for the treatment of metastatic prostate cancer. However, prostate cancer being primarily a heterogeneous tumor comprising hormone-dependent, hormone-sensitive, and hormone-insensitive cells, at least the latter remain unaffected by hormonal manipulations, thus making disease progression almost inevitable. In quest of a more comprehensive therapy we therefore studied the concept of early combined chemoendocrine therapy in a prospective randomized multicenter trial. The purpose of this study was to evaluate whether patients with previously untreated advanced prostate cancer benefit from combining total androgen blockade (TAB) with weekly epirubicin chemotherapy (E-TAB). From April 1988 to January 1991, 145 previously untreated patients with either metastatic (n = 117) or locally advanced (n = 28) histologically confirmed prostate cancer were randomly allocated to treatment with TAB by bilateral orchiectomy and flutamide 250 mg t.i.d. or TAB plus weekly epirubicin 25 mg/m2 i.v. for 18 weeks (E-TAB). The study endpoints were progression-free survival and overall survival. In addition the effects of treatment on quality of life were assessed by two methods. At regular intervals patients self-assessed ten qualities of physical, functional and emotional health using 5-point scales. In order to evaluate the time without disease progression and treatment-induced adverse effects, a modified Q-TWiST (quality-adjusted time without symptoms and toxicity) model was applied. At a median follow-up of 81 months, progression-free survival and overall survival in the TAB and E-TAB groups were 12 and 18 months (p < 0.02) and 22 and 30 months (p = 0.12), respectively. In patients with > 5 sites of bone metastasis (D2max), the corresponding periods were 9 and 14 months (p = 0.005) and 17 and 27 months (p = 0.06), respectively. Subjective quality of life assessment showed no impairment of quality of life by epirubicin treatment. Stage D and D2max patients treated with E-TAB had an average gain in Q-TWiST of 5 months (p = 0.098) and 8 months (p = 0.03), respectively, compared to the TAB treatment. Objective toxicities were generally mild with either treatment. In conclusion, the combination of TAB and epirubicin was well tolerated by patients with advanced prostate cancer and resulted in a significant extension of progression-free survival. This effect of E-TAB on objective treatment outcome was accompanied by prolonged time without treatment-induced adverse effects and tumor progression, i.e., time with good quality of life. Therefore, further studies with E-TAB appear warranted in patients with advanced prostate cancer.

Aged↗
PubMed1985

Free radical scavengers in mercuric chloride-induced acute renal failure in the rat.

Oxygen free radicals have recently been found to mediate cell injury after ischemia in the kidney. We sought to determine whether oxygen free radicals mediate damage in mercuric chloride (HgCl2)-induced acute renal failure, a toxic model of acute renal failure. Neither superoxide dismutase nor allopurinol, which scavenges or inhibits production of superoxide radical, respectively, provided protection against renal dysfunction after HgCl2. Similarly, the hydroxyl radical scavengers tryptophan, N-acetyl-tryptophan, and ascorbic acid were unable to protect against HgCl2. However, dimethylthiourea and dimethyl sulfoxide, both hydroxyl radical scavengers, were beneficial. Dimethylthiourea completely prevented the rise in plasma creatinine concentration after HgCL2. In control rats plasma creatinine concentration rose from 0.4 mg/dl to 3.2 +/- 0.8, 5.1 +/- 1.0, and 6.1 +/- 1.6 mg/dl at 24, 48, and 72 hours after HgCl2. Dimethylthiourea-treated rats had plasma creatinine concentration less than 0.5 mg/dl at all times. Furthermore, a mixture of HgCl2 and equimolar amounts of dimethylthiourea was less toxic than HgCl2 alone. Dimethyl sulfoxide attenuated the HgCl2-induced rise in creatinine concentration: 1.3 +/- 0.2, 3.2 +/- 0.3, and 3.1 +/- 0.2 mg/dl at 24, 48, and 72 hours after HgCl2. Measurement of kidney malondialdehyde content after HgCl2 provided no evidence for oxygen free radical-mediated lipid peroxidation. We conclude that there is no convincing role for oxygen free radicals in the pathogenesis of HgCl2-induced acute renal failure. The ability of dimethylthiourea and dimethyl sulfoxide to protect against HgCl2-induced renal dysfunction may be related to their ability to form complexes with Hg2+.

Acute Kidney Injury↗
PubMed2001

Duration of untreated psychosis and cognitive functioning in first-episode patients.

BACKGROUND: The "toxicity" model of duration of untreated psychosis (DUP) suggests that longer DUP will be associated with poorer performance on cognitive tests in first-episode patients. AIMS: To test this hypothesis on a sample of 113 patients in a community-based early intervention programme for psychosis. METHOD: Information was collected concerning a number of possible predictors of cognitive functioning including DUP. These were examined for their relation to performance on an extensive battery of cognitive tests administered shortly after the patients' admission to the programme. RESULTS: Although several variables such as gender, premorbid adjustment, education and handedness predicted cognitive functioning, no relation was found between DUP and performance on any component of the test battery. CONCLUSIONS: Findings do not provide support for a toxic effect of DUP on cognitive functioning. Other mechanisms through which DUP might affect outcome such as psychological engulfment, social support and adherence to medication are discussed.

Adolescent↗
PubMedDate not supplied

The study of oxidative stress in freshly isolated Ca(2+)-tolerant cardiomyocytes from the adult rat.

Cardiotoxicity studies using isolated heart cells are becoming increasingly advocated as a supplement to, and sometimes as a replacement for, whole heart or whole animal experimentation. In fact, the use of isolated cardiomyocytes has the great advantage of enabling mechanistic and comparative studies of compounds, which are directly toxic to cardiomyocytes. Since the 1970s, different procedures have been developed in order to obtain Ca(2+)-tolerant cardiomyocytes. The advances in this field will be reviewed and an optimised method to obtain freshly isolated Ca(2+)-tolerant cardiomyocytes from the adult rat for use in toxicological studies will be described. With this procedure, a high number of rod-shaped cells can be obtained (6-7 x 10(6)/heart corresponding to 70% of total number of cells). It is also possible to maintain cell viability, glutathione content and enzymatic activity of glutathione reductase (GR), glutathione peroxidase (GPX) and glutathione S-transferase (GST) in acceptable levels for 4 hours. Cardiotoxicity studies performed with isoproterenol (ISO) in the presence of copper and with the model toxic substance tert-butylhydroperoxide (t-BHP) demonstrate the importance of oxidative stress as a cardiotoxic mechanism elicited by these molecules. The results obtained are also good indicators for future applications of this methodology to other cardiotoxicity studies.

Animals↗
PubMed2002

The importance of light intensity in algal tests with coloured substances.

Current algal test protocols do not distinguish between chemical toxicity and growth inhibition due to physical shading when coloured substances like dyes are evaluated. To eliminate the interfering physical effect, we investigated the importance of light intensity and culture volume in the algal growth inhibition tests with Desmodesmus subspicatus and three selected dyestuffs. A photon flux density above light saturation is needed to prevent inhibition of algal growth solely due to the light absorption by dyes. Furthermore, a smaller culture volume and moderate shaking of the test flasks is advantageous in that these conditions decrease the influence of the light absorption. At 120 microE s(-1) m(-2), the shading effect of three tested dyes could be eliminated, up to a concentration of 100 mg l(-1). In a mixture with a blue dyestuff, the model toxicant potassium dichromate showed nearly the same EC50 as if applied alone, indicating that the impact of the dye was negligible. Also a small culture volume decreases the inhibition of the average growth rate of Desmodesmus. Thus, by increasing the light intensity and optionally also reducing the culture volume, this method allows a more direct measure of a potential inherent chemical toxicity of coloured substances to algae. Additionally, high light intensities and lower culture volumes result in lower coefficients of variation, which improves the sensitivity of the test for the statistical calculation of toxicity data.

Absorption↗
PubMed1993

Hypoxia and oxygen dependence of cytotoxicity in renal proximal tubular and distal tubular cells.

Ischemia and hypoxia are major causes of renal failure and altered oxygen supply may affect renal responses to toxic chemicals. In vitro experiments were designed to evaluate the susceptibility of isolated proximal tubular (PT) and distal tubular (DT) cells from rat kidney to brief periods of oxygen deprivation and to assess how variations in oxygen supply affect chemical-induced cytotoxicity. Isolated cells were incubated for 1 hr in either oxygen (95% O2/5% CO2), air (21% O2), or nitrogen (95% N2/5% CO2) atmosphere. PT cells exhibited no injury due to brief oxygen deprivation whereas DT cells exhibited moderate, but significant injury, indicating that DT cells are more susceptible than PT cells to hypoxic injury. The cytotoxicity of chemicals that alter cellular redox status [i.e. tert-butyl hydroperoxide (tBH), menadione, methyl vinyl ketone] and the cytotoxicity of "chemical hypoxia" [i.e. KCN + iodoacetic acid] were greatest in air, intermediate in oxygen, and lowest in nitrogen. In contrast, the cytotoxicity of the alkylating agent N-dimethylnitrosamine was independent of oxygen concentration and the cytotoxicity of p-aminophenol was related directly to oxygen concentration. The mechanism of the oxygen dependence of chemical injury was investigated further, employing tBH as a model toxicant. tBH metabolism was oxygen independent in both PT and DT cells. Depletion of cellular protein sulfhydryl groups by tBH increased with increasing oxygen concentration and lipid peroxidation due to tBH was inhibited in nitrogen but was not different in air as compared with oxygen. Although these processes may contribute to the much lower toxicity in nitrogen as compared with oxygen, it does not explain the higher toxicity in air as compared with that in oxygen. Other processes that predominate at lower oxygen concentrations but that only produce injury if enough oxygen is present are likely to be responsible for the enhanced susceptibility of both PT and DT cells to oxidants in air as compared with oxygen.

Air↗
PubMed1987

PVP-sieving curves as an estimate of glomerular hemodynamics in HgCl2 acute renal failure in the dog.

In the present study, the pathophysiologic role of glomerular hemodynamic factors in the early phase of HgCl2-induced acute renal failure is evaluated in the dog. This model of moderate ARF is characterized by a parallel fall in glomerular filtration rate (delta GFR, -43%) and renal blood flow (delta RBF, -38%) within the first three hours after HgCl2 administration. Glomerular hemodynamics were studied by analysis of PVP-sieving curves. There was a significant shift of these curves upward and to the right during the 3 hours that followed the injection of HgCl2. From this analysis, no arguments for tubular back-leak could be found. Mathematical analysis of the curves revealed a fall in effective filtration pressure (EFP) in presence of an unchanged glomerular ultrafiltration coefficient (Kf) (delta EFP, -40 +/- 4%; p less than 0.01; delta Kf, +5 +/- 1%; p greater than 0.05 vs. control). No major changes occurred in glomerular colloid osmotic pressure. Subsequently, the early fall of GFR in this toxic model of acute renal failure was essentially attributed to a decrease of effective filtration pressure due to either tubular obstruction and/or mainly to renal hemodynamic changes.

Acute Kidney Injury↗
PubMed2002

Culturing precision-cut human prostate slices as an in vitro model of prostate pathobiology.

Due to the complex morphology of the prostate, it was hypothesized that precision-cut tissue slices from human prostate would provide a unique in vitro model. Precision-cut slices were generated from zones of human prostate and their viability was assessed under conditions of different media for up to 120 h. Slices were also exposed to several concentrations of CdCI2, which was used as a model toxicant. Maintenance of both stromal and epithelial cells was noted; however, there was a gradual loss of luminal epithelial cells when the medium was not supplemented with dihydrotestosterone (DHT). Minimal leakage of lactate dehydrogenase occurred throughout the incubation. Prostate-specific antigen (PSA) was detected in the medium at all time points, although the rates of secretion fell over time. There was a loss of PSA-positive cells when the medium was not supplemented with DHT, consistent with a loss of luminal cells, whereas PSA-positive cells were maintained in the DHT-supplemented media. A proliferation of basal cells was observed in the presence of media containing 10% fetal bovine serum. Exposure of slices to CdCl2 demonstrated a dose-response effect ranging from proliferation to complete cellular necrosis. Given the retention of stromal-epithelial interactions and the use of acquired human tissue, prostate slices represent a unique in vitro model for investigating human prostate pathobiology.

Cadmium Chloride↗
PubMed1989

Fluorescence-based viability assay for studies of reactive drug intermediates.

Studies of drug toxicity, toxicologic structure-function relationships, screening of idiosyncratic drug reactions, and a variety of cytotoxic events and cellular functions in immunology and cell biology require the sensitive and rapid processing of often large numbers of cell samples. This report describes the development of a high-sensitivity, high-throughput viability assay based on (a) the carboxyfluorescein derivative 2'-7'-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF) as a vital dye, (b) instrumentation capable of processing multiple small (less than 100 cells) samples, and (c) a 96-well unidirectional vacuum filtration plate. Double staining of cultured peripheral blood mononuclear cells with BCECF and propidium iodide (PI) showed no overlap between PI+ (nonviable) and BCECF+ (viable) cells by flow cytometric analysis. Optimal conditions were developed for dye loading and minimizing physical cell damage and fluorescence quench during the assay procedure. The ratio of BCECF fluorescence to internal standard fluorescent particles was linear from 40 to greater than 20,000 cells with a signal:noise ratio of approximately 3 at 40 cells/well. Sulfamethoxazole hydroxylamine (SMX-HA) was used as a model toxic drug metabolite to explore the validity of the BCECF procedure. SMX-HA, but not its parent compound sulfamethoxazole, resulted in a dose dependent loss of cellular fluorescence and the parallel accumulation of PI+ nonviable cells. When compared to the currently used tetrazolium dye reduction viability assay, the BCECF method was 3-fold more sensitive, greater than 10-fold faster, and required 1/10-1/100 the cell numbers.

Cell Survival↗
PubMed2005

Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection.

Molecular differences between dopamine (DA) neurons may explain why the mesostriatal DA neurons in the A9 region preferentially degenerate in Parkinson's disease (PD) and toxic models, whereas the adjacent A10 region mesolimbic and mesocortical DA neurons are relatively spared. To characterize innate physiological differences between A9 and A10 DA neurons, we determined gene expression profiles in these neurons in the adult mouse by laser capture microdissection, microarray analysis and real-time PCR. We found 42 genes relatively elevated in A9 DA neurons, whereas 61 genes were elevated in A10 DA neurons [> 2-fold; false discovery rate (FDR) < 1%]. Genes of interest for further functional analysis were selected by criteria of (i) fold differences in gene expression, (ii) real-time PCR validation and (iii) potential roles in neurotoxic or protective biochemical pathways. Three A9-elevated molecules [G-protein coupled inwardly rectifying K channel 2 (GIRK2), adenine nucleotide translocator 2 (ANT-2) and the growth factor IGF-1] and three A10-elevated peptides (GRP, CGRP and PACAP) were further examined in both alpha-synuclein overexpressing PC12 (PC12-alphaSyn) cells and rat primary ventral mesencephalic (VM) cultures exposed to MPP+ neurotoxicity. GIRK2-positive DA neurons were more vulnerable to MPP+ toxicity and overexpression of GIRK2 increased the vulnerability of PC12-alphaSyn cells to the toxin. Blocking of ANT decreased vulnerability to MPP+ in both cell culture systems. Exposing cells to IGF-1, GRP and PACAP decreased vulnerability of both cell types to MPP+, whereas CGRP protected PC12-alphaSyn cells but not primary VM DA neurons. These results indicate that certain differentially expressed molecules in A9 and A10 DA neurons may play key roles in their relative vulnerability to toxins and PD.

1-Methyl-4-phenylpyridinium↗
PubMed2006

In vivo evaluation of plasmid DNA encoding OP-1 protein for spine fusion.

STUDY DESIGN: A posterolateral lumbar interbody arthrodesis animal model was selected to evaluate the percutaneous delivery of OP-1 plasmid DNA. OBJECTIVE.: To evaluate the feasibility of achieving ectopic bone formation using nonviral gene delivery with a minimally invasive technique, by coinjecting plasmid DNA encoding OP-1 with collagen into the paraspinal muscle. SUMMARY OF BACKGROUND DATA: Osteoinductive proteins show great promise for achieving spine fusion but suffer from poor bioavailability. Viral gene transfer can produce therapeutic and sustained levels of osteoinductive proteins to achieve osteogenesis in a variety of animal models. Toxicity and immunogenicity concerns, however, limit the appeal of viral gene therapy for spine fusion. METHODS: Single-level posterior lumbar arthrodesis was attempted at L5-L6 in 64 adult Sprague-Dawley rats bilaterally. OP-1 plasmid DNA was injected with and without collagen carrier above the L5 transverse process either percutaneously or after open surgery. Bone formation was evaluated at 2 and 4 weeks by manual palpation, posterolateral radiographs, and nondecalcified histology. Control animals received the rhOP-1 protein. RESULTS: Bone formation was detected histologically after the percutaneous and open surgical delivery of 25 microg or 500 microg, respectively, of OP-1 plasmid DNA (pVR1055-OP1) and collagen (bone formation = 75% and 50%), but was weaker than that observed after injection of 30 microg of rhOP-1 protein and collagen (bone formation = 100%). Single-level spine fusion was only achieved in groups receiving percutaneous OP-1 protein and collagen (30 microg protein, fusion rate = 100%) or high concentrations of OP-1 protein alone (40 microg protein, 100%), as confirmed through manual palpation, histology, and radiography. CONCLUSIONS.: These data confirm that OP-1 plasmid DNA can successfully generate bone formation in vivo.

Animals↗
PubMed2005

Molecular and pharmacological analysis of an octopamine receptor from American cockroach and fruit fly in response to plant essential oils.

Octopamine receptors from American cockroach, Periplaneta americana (Pa oa1), and fruit fly, Drosophila melanogaster (OAMB), were cloned and permanently expressed in HEK-293 cells, and found to activate adenylate cyclase activity and increase [Ca2+]i levels through G-protein coupled receptor signaling pathways. Sequencing information (GenBank accession number AY333178) and functional data of Pa oa1 were recently published. Saturation binding analysis with 3H-yohimbine was performed with Pa oa(1) and OAMB expressed in COS-7 cells. The K(d) values were determined to be 28.4 and 43.0 nM, respectively. B(max) was determined to be 11.8 and 8.04 pmol receptor/mg protein, respectively. Competitive binding data using cell membranes expressing either OAMB or Pa oa1 demonstrated significantly decreased binding activity in binding assays performed in the presence of plant essential oils, eugenol, cinnamic alcohol, and trans-anethole. Eugenol decreased cAMP level in HEK-293 cells expressing Pa oa1, but trans-anethole increased cAMP in HEK-293 cells expressing OAMB. All three chemicals increased [Ca2+]i level in both cell models. Toxicity data against fruit flies and American cockroaches demonstrated species differences in response to treatment with tested plant essential oils. The toxicity of tested chemicals against wild type and octopamine mutant (iav) fly strains suggested that an octopamine receptor mediates the toxicity of cinnamic alcohol, eugenol, trans-antehole, and 2-phenethyl propionate against fruit flies. Collectively, the data suggest a correlation between cellular changes induced by tested plant essential oils and their toxicity against fruit fly and American cockroach.

Adenylyl Cyclases↗
PubMed2003

Oxidation of 4-bromophenol by the recombinant fused protein cellulose-binding domain-horseradish peroxidase immobilized on cellulose.

A fused protein consisting of cellulose-binding domain (CBD) and horseradish peroxidase (HRP) was constructed and expressed in Escherichia coli. Refolded recombinant CBD-HRP (95% recovery yield) was bound to microcrystalline cellulose and applied for the oxidation of a model toxic phenol, 4-bromophenol (BP). Oxidation of BP by CBD-HRP resulted in the formation of dimers to pentamers as evidenced by mass spectrometry analysis. When immobilized, the vast majority of the oxidation products adsorbed to the cellulose matrix. CBD-HRP (0.75 pyrogallol units) bound to 0.1 g cellulose was packed in a column, connected to an HPLC pump and monitoring system, and column performance and capacity were studied under various operating conditions. When performance was studied as a function of BP loading rate at a constant H(2)O(2) loading rate of 1500 nmol/min, V(app) (max) and K(m) (app) were calculated to be 5.29 +/- 0.46 micromol mL min and 644.9 +/- 114.3 microM, respectively. Immobilized CBD-HRP exhibited enhanced stability to H(2)O(2) and oxidized considerably more BP than free CBD-HRP. Inclusion of gelatin, which suppresses product-dependent inactivation, further increased the amount of BP oxidation. These findings may have potential impact in terms of enzyme supply in high-rate treatment of wastewater contaminated with toxic phenols, since the susceptibility of peroxidases to both H(2)O(2) - and product-dependent inactivation demands continuous supply of fresh enzyme.

Cellulase↗