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PubMed1976

Sensitivity of environmental microorganisms to antimicrobial agents.

The sensitivity of different microorganisms, considered as typical representatives of the microflora of soil and water, was established to evaluate the influence of the nonmedical use of antimicrobial agents on bacterial ecology. Only seven strains, six chemoorganotrophs and one chemolithotroph, could be considered as relatively sensitive to the 21 antimicrobial compounds tested. The other 29 microorganisms may be regarded as resistant to most antimicrobial agents. Streptomyces were sensitive to high concentrations of active substances. Broad-spectrum antibiotics showed an effect on environmental bacteria similar to that on human pathogens. Cephalothin stimulated the growth of a Chlorella sp. From these experiments, it appears that spilled antimicrobial agents have little chance of causing an alteration in the microbial ecology.

Anti-Bacterial Agents↗
PubMed2001

Environment-sensitive hydrogels for drug delivery.

Environmentally sensitive hydrogels have enormous potential in various applications. Some environmental variables, such as low pH and elevated temperatures, are found in the body. For this reason, either pH-sensitive and/or temperature-sensitive hydrogels can be used for site-specific controlled drug delivery. Hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors as well as drug delivery systems. Light-sensitive, pressure-responsive and electro-sensitive hydrogels also have the potential to be used in drug delivery and bioseparation. While the concepts of these environment-sensitive hydrogels are sound, the practical applications require significant improvements in the hydrogel properties. The most significant weakness of all these external stimuli-sensitive hydrogels is that their response time is too slow. Thus, fast-acting hydrogels are necessary, and the easiest way of achieving that goal is to make thinner and smaller hydrogels. This usually makes the hydrogel systems too fragile and they do not have mechanical strength necessary in many applications. Environmentally sensitive hydrogels for drug delivery applications also require biocompatibility. Synthesis of new polymers and crosslinkers with more biocompatibility and better biodegradability would be essential for successful applications. Development of environmentally sensitive hydrogels with such properties is a formidable challenge. If the achievements of the past can be extrapolated into the future, however, it is highly likely that responsive hydrogels with a wide array of desirable properties can be made.

Animals↗
PubMed1996

Exposure and sensitization to environmental allergen of predominantly Hispanic children with asthma in San Diego's inner city.

BACKGROUND: Environmental living conditions co-sorting with economic status may influence the disease morbidity rate of childhood asthma in ethnic minority urban poor populations. OBJECTIVES: This study was carried out to assess exposure and sensitization to environmental allergens in southeast San Diego children with current asthma-related symptoms and to determine the utility of environmental control measures. METHODS: Children, 9 to 12 years old, with current asthma-related symptoms were identified and enrolled at four school sites. Skin prick testing with aeroallergens was performed, and allergen in collected dust (from mattresses, pillows, and bedroom carpets) was quantified by enzyme immunoassay. Environmental control instruction and products were provided. RESULTS: Of 41 subjects who underwent skin testing, 51.2% were reactive to environmental allergens (39% to mite, 22% to cockroach, and 9.8% to cat). Mean allergen levels for sensitized subjects were: Der p 1 (11 subjects), 18,722 ng/gm dust; Der f 1 (8 subjects), 5345 ng/gm dust; Fel d 1 (3 subjects), 214 ng/gm dust; Bla 1 (8 subjects), 7.15 U/gm dust; and Bla 2 (8 subjects) 7.13 U/gm dust. Environmental allergen exposure levels were not significantly different between sensitized and nonsensitized subjects. Environmental control measures for mite exposure were completed in six homes of sensitized subjects. One month after treatment, allergen levels fell 91.2% for Der p 1, 98.9% for Der f 1, and 88.2% for Fel d 1. One year after treatment, mite and cat allergen levels remained low. Environmental control had no consistent impact on cockroach allergen levels. CONCLUSION: Environmental allergen sensitization and exposure may be cofactors contributing to increased disease severity in urban poor populations.

Air Pollutants↗
PubMed1998

[The non-specific environmental syndromes MCS (Multiple Chemical Sensitivity), IEI (Idiopathic Environmental Intolerance) and SBS (Sick Building Syndrome)].

This review starts with a clinical description of the most common unspecific environmental diseases, such as Multiple Chemical Sensitivities (MCS), Idiopathic Environmental Intolerances (IEI) and Sick Building Syndrome (SBS). These syndromes are very controversial discussed between scientific medicine and "clinical ecology". In addition, they have fundamental similarities to Chronic Fatigue Syndrome (CFS) and Fibromyalgia. Finally the spectrum of therapeutic approaches is discussed.

Desensitization, Immunologic↗
PubMed1993

Changes in phenotypically distinct phagocyte subpopulations during nonspecific modulation of contact sensitization.

Environmental influences are increasingly recognized as nonspecific modulators triggering and aggravating allergic diseases. To obtain better insight into the pathomechanisms of these nonantigen-specific phenomena, we studied the augmenting and inhibitory effects of croton oil and glucocorticosteroid (GC) on the induction of murine allergic contact dermatitis. Application of the irritant croton oil simultaneously with the sensitization dose of the contact allergen oxazolone strongly amplified the inflammatory reaction (measured as ear swelling) during the effector phase. Immunohistologically, this effect correlated with an increased percentage of MRP8- and MRP14-positive phagocytes in the infiltrate of the early inflammatory reaction 8 h after sensitization with oxazolone plus croton oil as compared to oxazolone alone (62 vs. 27%; p < 0.05). Intravenously administered GC was used as an inhibitor of contact sensitization. The suppressive effect of GC on sensitization was dependent on the time of its application: suppression of the inflammatory reaction during the effector phase was clearly more pronounced when GC had been injected 1 day as compared to 1 h before sensitization. Correspondingly, the percentage of BM8-positive macrophages in the infiltrate of the early inflammatory reaction 8 h after sensitization was differentially decreased depending on the time of GC application: suppression of the percentage of BM8-positive macrophages was clearly more pronounced when GC had been injected 1 day as compared to 1 h before sensitization (17 vs. 25%; base value without GC 35%; p < 0.05). Furthermore, the percentage of BM8-positive macrophages in the inflammatory infiltrate of the effector phase was increased when sensitization had been enhanced by concomitant irritant contact dermatitis (47 vs. 59%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Biomarker monitoring for health risk based on sensitivity to environmental mutagens.

Ongoing human and environmental genome programs have generated a tremendous amount of information regarding the genetic basis for human disease. The information can be used to enhance existing bioassays, as well as to develop new bioassays for improving human monitoring with the goal of disease prevention. In this review, some biomarkers that can be used for the purpose are presented, with an emphasis on using biomarkers to monitor human sensitivity to environmental mutagens. The application of biomarkers in clarifying the role of inherited and acquired susceptibility for developing environmental disease will be discussed. We emphasize the use of biomarkers that can detect mutagen sensitivity and DNA repair deficiency in the humans as an indication of susceptibility to disease. Such sensitivity can be either genetically determined or acquired from the exposure to environmental mutagens.

Biological Assay↗
PubMed2004

A resource allocation model describing consequences of artificial selection under metabolic stress.

Long-term selection on production results in increased environmental sensitivity. This often is expressed through decreased fertility and increased health problems. The phenomenon has been described in all common farm animal species. One theory is that potential resource intake is insufficient to express production potential. Additional resources are drawn away from fitness-related traits, such as fertility and health, to further increase observed production. In addition, resources for maintaining fitness depend on the demands by the environment. In a harsh environment, more resources are required for fitness-related traits than in an optimal environment. Literature results show that selection in an optimal environment will increase sensitivity to less optimal environments. The objectives of this paper were to increase understanding of the underlying mechanism behind the development of environmental sensitivity and to gain insight into correlated response(s) when selection is on observed production. A resource allocation model was defined where observed production depended on production potential, resource intake potential, and the allocation of resources to production or fitness, including maintenance, health, and reproduction. Penalties for reproductive performance and probability of survival were included when the proportion of resources assigned to fitness dropped below a certain, environment-related, threshold. Mass selection was practiced on observed production during 40 generations using stochastic simulation. Depending on the heritabilities of the underlying components and on the environment, selection on observed production resulted in a decrease in reproductive rate and in the development of environmental sensitivity when resource intake becomes limiting. Correlations of observed production with underlying components changed across generations, following a nonlinear pattern. The proposed model is simple, but increases the understanding of underlying mechanisms and consequences of selection for production when resources are limiting.

Animal Husbandry↗
PubMed2005

Three distinct read-out modes for enzyme activity can operate in a semi-wet supramolecular hydrogel.

Assays of hydrolytic enzyme activity, such as of glycosidases and phosphatase, as well as several proteases, using a semi-wet supramolecular hydrogel array composed of a glycosylated amino acetate are described. It has been demonstrated that the microcavity formed by gel fibrils is suitable to immobilize native enzymes without denaturation under semi-wet conditions, and thus the nanofiber has been rationally used as a sensing domain to monitor enzymatic reactions. By using a fluorogenic substrate, reducing the size of the hydrogel can significantly improve the problem of suppressed diffusion within the gel matrix thus making the hydrogel a promising semi-wet matrix for evaluating enzyme activity. Confocal laser scanning microscopy observations have shown that an environmentally sensitive fluorescent probe accumulates in the hydrophobic domain of the gel fiber and emits fluorescence more strongly upon hydrolytic cleavage of the substrate peptides. Not only a simple environmentally sensitive probe but also a FRET (fluorescence resonance energy transfer)-type read-out mode can be devised to analyze the enzymatic hydrolysis-triggered redistribution of the probe between the nanospace and the nanofiber to accomplish a more clearly distinguished enzyme assay. Thus, it is clear that three distinct read-out modes, that is, 1) fluorogenic substrates, 2) substrates bearing an environmentally sensitive probe, or 3) a substrate exhibiting FRET, can operate under the semi-wet hydrogel conditions used in these investigations. In addition, owing to the unique properties of the present supramolecular hydrogel in semi-wet conditions, that is, its phase-segregation properties and dynamics, the supramolecular substrate/enzyme array has successfully been used for high-throughput screening of single and multiple enzymes based on their activity, lysate analysis, and quantitative evaluation of inhibitor potency and selectivity.

Enzyme Inhibitors↗
PubMed1993

Behavior of Cys-707 (SH1) in myosin associated with ATP hydrolysis revealed with a fluorescent probe linked directly to the sulfur atom.

4-Fluoro-7-sulfamoylbenzofurazan (ABDF) has a rather small fluorophore that is linked directly to the sulfur atom of thiols without a flexible alkyl chain (Imai, K., and Toyo'oka, T. (1987) Methods Enzymol. 143, 67-75). In the present study I examined the fluorescent and chemical properties of ABDF as an environmentally sensitive probe for Cys-707 (SH1) of myosin subfragment-1 (S-1) to monitor the behavior of SH1 associated with ATP hydrolysis. ABDF was very stable to long irradiation and nonfluorescent before attachment to thiols, permitting the continuous monitoring of the labeling reaction. The fluorophore was useful as an environmentally sensitive probe for thiol groups in proteins. SH1 of S-1 was specifically labeled with ABDF. When ATP, adenyl-5'-yl imidodiphosphate, and ADP were added to the labeled S-1 (ABD-S-1), the fluorescence intensity at 500 nm increased by 110, 66, and 53%, respectively. Binding of actin to ABD-S-1 resulted in a decrease in the fluorescence by 30%. The fluorophore attached to SH1 was found to be located in a more hydrophobic environment in the presence of ATP than in the absence of ligand. KI fluorescence quenching studies suggested that the binding of ATP causes a movement of SH1 toward a more hydrophobic protein interior, whereas it goes back to the opposite direction after ATP hydrolysis. Thus, ABDF is very useful as an environmentally sensitive fluorescent probe for SH1 that monitors ligand-induced changes in the behavior of the thiol.

Acrylamide↗
PubMed2005

Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder that displays both sporadic and inherited forms. Exposure to several common environmental toxins acting through oxidative stress has been shown to be associated with PD. One recently identified inherited PD gene, DJ-1, may have a role in protection from oxidative stress, thus potentially linking a genetic cause with critical environmental risk factors. To develop an animal model that would allow integrative study of genetic and environmental influences, we have generated Drosophila lacking DJ-1 function. Fly DJ-1 homologs exhibit differential expression: DJ-1beta is ubiquitous, while DJ-1alpha is predominantly expressed in the male germline. DJ-1alpha and DJ-1beta double knockout flies are viable, fertile, and have a normal lifespan; however, they display a striking selective sensitivity to those environmental agents, including paraquat and rotenone, linked to PD in humans. This sensitivity results primarily from loss of DJ-1beta protein, which also becomes modified upon oxidative stress. These studies demonstrate that fly DJ-1 activity is selectively involved in protection from environmental oxidative insult in vivo and that the DJ-1beta protein is biochemically responsive to oxidative stress. Study of these flies will provide insight into the critical interplay of genetics and environment in PD.

Amino Acid Sequence↗
PubMed1995

PCR for bioaerosol monitoring: sensitivity and environmental interference.

The PCR technique has potential for use in detection of low concentrations of airborne microorganisms. In this study, the sensitivity of PCR and its susceptibility to environmental interference were assessed with Escherichia coli DH1 as the target organism. Air samples, containing environmental bioaerosols, were collected with AGI-30 samplers and seeded with E. coli DH1 cells. Parallel studies were performed with cells seeded into the sampler prior to collection of air samples to determine the effects of environmental inhibition and sampling stress on the PCR assay. Baseline studies were also performed without environmental challenge or sampling stress to compare two protocols for cell lysis, solid phase and freeze-thaw. Amplification of a plasmid target sequence resulted in a detection limit of a single bacterial cell by the freeze-thaw and solid-phase methods within 5 and 9 h, respectively. With a genomic target, the sensitivity of the solid-phase method was 10-fold lower than that of freeze-thaw. Samples which contained 10(3) to 10(4) CFU of environmental organisms per m3 inhibited amplification; however, a 1/10 dilution of these samples resulted in successful amplifications. No difference in sensitivity of the PCR assay was obtained as a result of sampling stress, although a 10-fold decrease in culturability was observed. A field validation of the protocol with genomic primers demonstrated the presence of airborne E. coli and/or Shigella spp. in outdoor samples. This study indicates that the PCR method for detection of airborne microorganisms is rapid and sensitive and can be used as an alternative method for air quality monitoring.

Aerosols↗
PubMed1987

In vitro sensitivity of environmental isolates of pathogenic dematiaceous fungi to azole compounds and a phenylpropyl-morpholine derivative.

The in vitro sensitivity (minimum inhibitory concentrations; MICs) of 42 environmental isolates of pathogenic dematiaceous fungi to 7 azole compounds, viz. thiabendazole, ketoconazole, miconazole, econazole bifonazole, Bay n 7133, Bay 1 9139 and phenylpropyl-morpholine derivative, Ro14-4767/002 was studied by an agar dilution method using Emmon's Sabouraud dextrose agar (ESDA) as the culture medium. The isolates of Fonsecaea pedrosoi, Cladosporium carrionii, Exophiala jeanselmei and Ramichloridium subulatum were most sensitive to bifonazole with mean MICs of 0.06 microgram/ml or less; Phialophora verrucosa had an MIC of 0.05 microgram/ml to ketoconazole and Ro14-4767/002, respectively. Ochroconis sp had an MIC of 0.025 microgram/ml to Ro14-4767/002 and Cladosporium tennuisimum 0.39 microgram/ml to ketoconazole. Econazole and thiabendazole also showed good antifungal activity. The fungi were relatively resistant to the more recently developed azoles, viz. Bay n 7133 and Bay 1 9139, the later failing to inhibit C. tennuisimum at a concentration of 100 micrograms/ml. The minimum fungicidal concentrations (MFC) of the drugs were mostly within 2 to 8 fold of the MICs.

Animals↗
PubMed1981

Genetical variation for enzyme activity in a population of Drosophila melanogaster. VII. Genotype-environment interaction for alcohol dehydrogenase (ADH) activity.

Genotype-environment interaction was detected for ADH activity amongst a set of 18 highly inbred lines of Drosophila melanogaster which had been extracted from the laboratory population, "Texas". The genotype-environment interaction for ADH activity was not wholly associated with genotype-environment interaction for body weight or total protein level. Detailed analyses of the responses of the individual inbred lines in ADH activity in relation to the environmental index, ej and following the procedure of Jinks and Pooni (1979), showed substantial diversity in the form of response. Lines homozygous for the AdhF allele were more environmentally sensitive than AdhS/S lines. Amongst the 16 AdhS/S lines, models of linear, quadratic or two intersecting-straight-lines were used to illustrate the varied responses of genotypes to the environment. The heterogeneity in the response characteristics of the inbred lines was attributed to variations in the conditions of culture media normally present within populations and laboratories. Moreover the non-linear responses shown by some lines to the environment are consistent with a model of genotype-environment interaction for ADH activity mediated by varied genotype-specific sensitivities to different environmental factors.

Alcohol Oxidoreductases↗
PubMed1999

Olfaction and symptoms in the multiple chemical sensitivities syndrome.

Whereas most idiosyncratic environmental sensitivity complaints do not fit known diagnoses, the multiple chemical sensitivities syndrome (MCS) is an extreme presentation that has defined diagnostic criteria. MCS symptomatics claim that they acquired a sensitized state as the result of a chemical exposure, usually to a solvent or pesticide, but not to a fragrance. Before this exposure, they did not experience symptoms. Following sensitization, symptoms increasing in number and severity with time are attributed by the MCS symptomatic to various exposures that are innocuous to most individuals. Although phenomenological studies have provided no evidence that particular odors elicit MCS symptoms, low levels of fragrances and perfumes are frequently associated with the reporting of MCS symptoms. This evaluation examines proposed mechanisms by which odorants and fragrances might cause either sensitization or elicitation of MCS symptoms, including altered odor sensitivity, primary irritancy or irritancy-induced upper airway reactivity, neurogenic switching of trigeminal irritancy signals, time-dependent sensitization and limbic kindling, CNS toxicity, and various psychiatric conditions. In no case was there persuasive evidence that any olfactory mechanism involving fragrance underlies either induction of a sensitized state or the triggering of MCS symptoms. Fragrances and other odorants could, however, be associated with symptoms as claimed by MCS symptomatics, because they are recognizable stimuli, but fragrance has not been demonstrated to be causal in the usual sense.

Environmental Exposure↗
PubMed1999

Intradermal testing for food and chemical sensitivities: a double-blind controlled study.

BACKGROUND: Confirming adverse reactions to foods and chemicals is fundamental in providing a basis for diagnosis and treatment of patients with reported environmental sensitivities. Provocation-neutralization testing is widely used in this respect but has not been thoroughly evaluated, therefore remaining a controversial and unproven technique. OBJECTIVE: This study investigated the validity of intradermal testing for evaluation of reported adverse reactions to a variety of incidents within the patient population at the Nova Scotia Environmental Health Centre. METHODS: A total of 132 people who were referred to the Nova Scotia Environmental Health Centre, a dedicated government-funded research and treatment facility for suspected environmental sensitivities, were tested by the technique of provocation-neutralization by the guidelines set out by the American Academy of Environmental Medicine. A panel of 13 foods, 9 chemicals, and 4 placebos (normal saline solution) was evaluated in a double-blind, randomized study. Symptoms and skin reactions were recorded, and response rates were determined for all substances, including saline solution injections. RESULTS: Seventy percent of the patients reported symptoms to 1 or more of the 4 saline solution injections. In comparison, 15% of patients experienced a skin reaction (wheal) to 1 or more injections of saline solution. Only 5% of individuals experienced a wheal to more than 1 saline solution injection, although 40% of the patients reported symptoms to more than 1 saline injection. Patients who experienced 1 or more reactions (wheal or symptoms) to saline solution were more reactive to injected allergens, on average reacting to 67% of active substances. Patients who experienced no reaction to the saline solution did experience a reaction to 48% of injected substances on average. Reaction by symptoms to foods, chemicals, and normal saline solution showed a random pattern, although wheal reactions showed a distinct pattern. Subsequent observations have indicated that experiencing no reaction to previous saline solution injections does not accurately predict response to saline solution in later testing. Some individuals who did not experience a reaction to saline solution in an initial screening later experienced a reaction to saline solution during further testing. CONCLUSIONS: Provocation of symptoms in usual testing conditions is not a useful tool for discriminating between reactions to saline solution and reactions to specific chemicals or foods. Skin response alone may be a more reliable indicator and will require cross-validation with other tests, such as oral and inhalation challenges and comparison with a control population. Heightened sensitivity and chaotic responses may be a feature of chemical sensitivity. Meanwhile, the results of provocation-neutralization testing, using symptoms alone as an indicator of neutralization, should not be used as a basis for clinical intervention.

Adolescent↗
PubMed2000

Mutagen sensitivity and environmental exposures as contributing causes of chromosome 3p losses in head and neck cancers.

The interaction between environmental exposures and host susceptibility may lead to specific mutational events within head and neck squamous cell carcinoma (HNSCC). Furthermore, this interplay may determine not only the probability of cancer development but also the biologic characteristics of the tumor once it occurs. To better understand the relationship of mutagen sensitivity and tobacco and/or alcohol consumption on HNSCC carcinogenesis, we examined loss of heterozygosity on chromosome 3p in 58 HNSCCs using 10 microsatellite markers. Mutagen sensitivity was determined in vitro by quantitating bleomycin-induced chromatid breaks utilizing peripheral blood lympocytes from respective patients. Forty-six of the 58 invasive cancers showed allelic loss at one or more loci. Consistent with previous investigations, three discrete regions of deletions were identified: 3p13-14.2, 3p21.1-21. 2, and 3p25.1-26.1. The frequency and types of deletions were dependent upon tobacco and alcohol exposures. The distal region of 3p but not the remaining two regions was most frequently influenced by tobacco exposure. In contrast, heavy alcohol use when combined with tobacco use was associated with whole-arm loss of 3p rather than identifiable site-specific damage. Furthermore, this combined influence of alcohol and tobacco exposures on whole-arm loss was most apparent in those patients who expressed mutagen-sensitivity; the odds ratio of whole-arm loss increasing from 2.67 (95% CI 0. 21-33.49) in those individuals who were mutagen resistant to 13.5 (95% CI 1.3-136.0; P = 0.02 by Fisher's exact test) in those who were mutagen sensitive. An assessment of clinical parameters in this population demonstrated that patients with whole-arm loss were more likely to present with cervical lymph node metastases and advanced stage disease than patients with partial losses. Results indicate that various environmental exposures as well as the expression of mutagen sensitivity will influence the types of chromosome 3p allelic losses in head and neck cancers as well as the behavior of disease once it develops.

Alleles↗