ABSTRACT
Recent concerns regarding the impact of traditional synthetic pesticides on nontarget organisms have generated demand for alternative products with lower environmental impact. This demand has led to increasing focus on plant essential oils as sources of new biopesticides. In this study, we demonstrate that the essential oil of the Alaskan yellow cedar, Cupressus nootkatensis (D. Don) Spach, has activity against hybrid imported fire ant workers, Solenopsis invicta Buren × Solenopsis richteri Forel. In digging assays, ants were repelled by nootka oil and digging continued to be suppressed by nearly 50% in nootka oil-treated sand aged 6 mo in the laboratory. Higher worker mortality was also observed in contact and fumigation assays compared to control checks. In a field drench test, mortality of mounds treated with nootka oil lagged behind mounds treated with bifenthrin treatment for 7 wk, but both nootka oil and bifenthrin had higher mortality than the untreated check at the end of the 12-wk evaluation period. In a band application evaluation, nootka oil plots maintained a 90-95% reduction in fire ant mounds from the 2nd to 17th wk, when new mounds began to intrude on the field plots. The quarantine-approved bifenthrin band treatment maintained 100% control from the 2nd to 24th wk. Although the formulation tested here did not perform to Federal Imported Fire Ant Quarantine standards, other formulations may enable this product to reach 100% control. In addition, nootka oil could be beneficial in situations where ant suppression rather than complete quarantine elimination is the management goal.
Subject(s)
Ants , Cupressus/chemistry , Insect Control , Insecticides , Oils, Volatile , Pyrethrins , AnimalsABSTRACT
In this study we investigated whether a reduction in neutrophil elastase activity in mice would alter the development of ultraviolet B or chemically induced skin tumors. A mutant strain of neutrophil elastase-deficient mice was developed by crossing beige mice with SKH 1 hairless mice. Ultraviolet irradiation three times per week for 20 wk developed an average of 10 tumors per normal mouse, whereas elastase-deficient hairless mice receiving the same treatment developed only 0.4 tumors per mouse. Benzopyrene administered topically for 20 wk resulted in an average of seven tumors per control mouse, while similar treatment to elastase-deficient hairless mice reduced the tumor count to 0.2 per mouse. Two small molecular weight elastase inhibitors, which were shown to inhibit mouse neutrophil elastase, were administered subcutaneously to normal SKH-1 mice during 16 wk of ultraviolet B exposure. Both inhibitors significantly reduced the incidence of ultraviolet B-induced tumors. When control and elastase-deficient mice were immunized with 2,4,6-trinitrochlorobenzene and oxazolone, both molecules elicited a significant contact hypersensitivity response. Ultraviolet B irradiation prior to immunization at a nonirradiated site completely suppressed the induction of contact hypersensitivity in both the normal and the deficient mice, suggesting that prevention of systemic immunosuppression was not the reason for the resistance to skin tumors observed in the elastase-deficient mice. The results suggest that neutrophil elastase can be an important factor in squamous cell tumor development.
Subject(s)
Leukocyte Elastase/antagonists & inhibitors , Skin Neoplasms/prevention & control , Animals , Benzopyrenes , Dermatitis, Contact/prevention & control , Genetic Predisposition to Disease , Kinetics , Mice , Mice, Hairless/genetics , Neoplasms, Radiation-Induced/prevention & control , Oligopeptides/pharmacology , Skin Neoplasms/chemically induced , Ultraviolet RaysABSTRACT
The purpose of this study was to compare the level of dyspnoea with and without the use of 5-cc saline instillation prior to endotracheal suctioning of mechanically ventilated adults. A crossover, quasi-experimental design was used. Seventeen alert, mechanically ventilated adults were asked to rank their level of dyspnoea using the vertical visual analogue scale at specific time intervals surrounding two suctioning events. Saline was randomly assigned to be instilled prior to one of two suctioning episodes. Dyspnoea was ranked immediately after suctioning, and at 10-, 20-, and 30-minute intervals. Data were analyzed using repeated measures analysis of variance with time of measure (immediately after suctioning, 10-, 20-, and 30-minute intervals) and treatment type (with saline versus without saline instillation). The level of dyspnoea based on treatment type (with or without saline) was non-significant. Treatment type by age group interaction was significant (F(1, 15) = 5.41, P = 0.034). The nature of the interaction revealed that older patients (< or = 60 years of age) experienced less dyspnoea without saline prior to suctioning and greater dyspnoea with saline instillation as compared to the younger subjects (<60 years of age). This study documented no beneficial effects of saline. However, it did demonstrate that saline instillation might precipitate a significantly increased level of dyspnoea for up to 10 minutes after suctioning in patients older than 60 years of age. Recommendations based on the results of this study would be to avoid the use of saline instillation prior to suctioning.
Subject(s)
Dyspnea/etiology , Intubation, Intratracheal , Respiration, Artificial , Sodium Chloride/therapeutic use , Adult , Age Factors , Cross-Over Studies , Dyspnea/prevention & control , Humans , Instillation, Drug , Middle Aged , Sodium Chloride/administration & dosage , SuctionABSTRACT
Because of the changes in our healthcare system, some clinical nurse specialists (CNSs) are having to expand their traditional roles of clinician, educator, consultant, leader, and researcher to include case management activities. The CNSs at Promina Gwinnett Health System in Lawrenceville, Georgia, have combined CNS and case manager activities and have adopted the title "CNS/Outcomes Coordinator." The CNS/Outcomes Coordinator is responsible for coordinating patient care, promoting team collaboration, and facilitating communication. To inform the healthcare team of the CNS/Outcomes Coordinator's patient responsibilities, the CNS/Outcomes Coordinators developed a Coordinated Care Classification System. This article describes how coordinating patient care, promoting team collaboration, and facilitating communication can be enhanced by the use of a classification system.
Subject(s)
Case Management/organization & administration , Communication , Continuity of Patient Care/organization & administration , Diagnosis-Related Groups/classification , Job Description , Nurse Clinicians/organization & administration , Outcome Assessment, Health Care/organization & administration , Adult , Cooperative Behavior , Humans , Interprofessional Relations , Male , Models, Organizational , Nursing Staff/organization & administration , Nursing Staff/psychologySubject(s)
Aminopterin/analogs & derivatives , Folic Acid/analogs & derivatives , Aminopterin/chemical synthesis , Aminopterin/pharmacology , Folic Acid/chemical synthesis , Folic Acid/pharmacology , Folic Acid Antagonists , Lacticaseibacillus casei/drug effects , Lacticaseibacillus casei/enzymology , Lacticaseibacillus casei/metabolism , Pediococcus/drug effects , Streptococcus/drug effects , Structure-Activity Relationship , Tetrahydrofolate Dehydrogenase/metabolism , Tetrahydrofolates/metabolism , Thymidylate Synthase/antagonists & inhibitors , Thymidylate Synthase/metabolismABSTRACT
Thirty-five infants weighing less than 1500 g at birth were fed four commercial formulas (A-D) varying in polyunsaturated fatty acid composition (32 per cent linoleic acid in A and B and 12 per cent linoleic acid in C and D) and in iron content (smaller than 1.0 in A and B; 12 to 12 mg per liter in B and D). Infants receiving formula B showed significantly lower hemoglobins (p smaller than 0.01) and higher reticulocyte counts (p smaller than 0.005) than infants fed the other three formulas. Infants receiving the two formulas with higher concentrations of unsaturated fatty acids (A and B) showed significantly greater hydrogen-peroxide-induced hemolysis (p smaller than 0.001) than those given diets containing lower amounts. Infants in groups A and B also had lower serum tocopherol concentrations. Infant red-cell membranes are altered by the increased amounts of polyunsaturated fatty acids and iron in the diet. It appears that the development of vitamin E deficiency anemia occurs in infants receiving iron supplementation.
Subject(s)
Anemia, Hemolytic/etiology , Dietary Fats/administration & dosage , Infant Food , Infant, Premature, Diseases/etiology , Iron/adverse effects , Vitamin E Deficiency/complications , Anemia, Hemolytic/blood , Diet , Erythrocyte Count , Fatty Acids, Unsaturated , Food, Fortified , Hemoglobinometry , Hemolysis , Humans , Hydrogen Peroxide/pharmacology , Infant , Infant Nutritional Physiological Phenomena , Infant, Newborn , Infant, Premature, Diseases/blood , Linoleic Acids , Reticulocytes , Vitamin E/blood , Vitamin E Deficiency/bloodABSTRACT
PURPOSE: In vitro data were collected to measure torque-force values of an internal distraction device. The measurements were correlated with in vivo torque readings in an attempt to better understand the force required to distract the osteogenic bone callus of the human mandible during distraction osteogenesis. METHODS AND MATERIALS: Five internal craniofacial distraction devices were mounted on an apparatus to test load limits and torque measurements. The apparatus aligned the devices so that weight provided a force opposite and parallel to the vector of distraction. Weights were added in 5-lb increments, and the devices were activated 0.5 mm for each torque reading. Torque readings were obtained from a calibrated torque wrench. Measurements were plotted on a graph and correlated with clinical torque readings obtained from 8 patients undergoing mandibular lengthening. RESULTS: The average torque for distracting the human mandible 0.5 mm twice a day was 4.2 +/- 1.6 Newton-centimeters (N-cm). The average slope of the in vitro data shows that 4.2 N-cm of torque is equivalent to a force of 35.6 N. The average force of device failure was 235.8 N. CONCLUSION: Torque-force diagrams offer an effective means for calibrating safety margins and load capabilities for internal distraction devices. Quantification of axial forces encountered in mandibular lengthening will help contribute to the overall understanding and biomechanics of mandibular distraction osteogenesis.
Subject(s)
Dental Stress Analysis , Mandible/physiology , Mandible/surgery , Mandibular Advancement/instrumentation , Osteogenesis, Distraction , Adolescent , Adult , Child , Female , Humans , Male , TorqueABSTRACT
Borrelia burgdorferi, the causative agent of Lyme disease, expresses on its surface two decorin binding adhesins, DbpA and DbpB. Previous studies have demonstrated that vaccination of mice with DbpA provided protection against challenge with heterologous Borrelia strains despite considerable sequence variability among DbpA in these strains. We have now examined the importance of individual amino acid residues in DbpA for decorin binding. We demonstrated that chemical modification of lysine residues resulted in loss of ligand binding activity. Of the 27 lysine residues in native DbpA from strain 297, 6 are present in most and 5 are conserved in all 30 DbpA sequences examined so far. Analysis of recombinant DbpA in which individual lysine residues have been mutated to alanine suggested that three of the conserved residues distributed throughout the DbpA sequence are required for decorin binding. These mutants lost their ability to bind decorin in Western ligand blot assay and bound reduced amounts of decorin in an ELISA. Furthermore, these mutant DbpA proteins did not inhibit the adherence of B. burgdorferi to a decorin substrata, and they did not recognize decorin in an extracellular matrix established by human fibroblast cultures. We conclude that the three lysine residues Lys-82, Lys-163, and Lys-170 are crucial for the binding of DbpA to decorin.
Subject(s)
Bacterial Adhesion/genetics , Borrelia burgdorferi Group/physiology , Escherichia coli Proteins , Lysine/metabolism , Proteoglycans/metabolism , RNA-Binding Proteins , Amino Acid Sequence , Animals , Base Sequence , Cells, Cultured , DEAD-box RNA Helicases , DNA Primers , Decorin , Extracellular Matrix Proteins , Fibroblasts/microbiology , Humans , Lysine/chemistry , Mice , Mutagenesis, Site-Directed , Protein Binding , RNA Helicases/chemistry , RNA Helicases/genetics , RNA Helicases/metabolism , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sequence Homology, Amino AcidABSTRACT
The zebrafish (Danio rerio) is assuming prominence in developmental genetics research. By comparison, little is known of tumorigenesis and nothing is known of carcinogen metabolism in this species. This study evaluated the ability of zebrafish to metabolize a well-characterized human carcinogen, aflatoxin B1 (AFB1), to phase I and phase II metabolites and assessed hepatic AFB1-DNA adduction in vivo. Fish i.p. injected with 50-400 micrograms [3H]AFB1/kg body wt displayed a linear dose response for hepatic DNA binding at 24 hr. AFB1-DNA adduct levels among treatments showed no statistical difference over the period from 1 to 21 days after injection, suggesting poor adduct repair in this species. DNA binding in female fish was 1-7-fold higher than that in males (p < 0.01). An in vitro AFB1 metabolism assay verified that zebrafish liver extracts oxidize AFB1 to the 8,9-epoxide proximate electrophile (Km = 79.0 +/- 16.4 microM, Vmax = 11.7 +/- 1.4 pmol/min/mg protein at 28 degrees C). The excretion of AFB1 and its metabolites was also examined by HPLC. As is typical of other fish studied, major metabolites excreted were aflatoxicol (AFL) and aflatoxicol-glucuronide (AFL-g), followed by unreacted AFB1. AFL appeared as early as 5 min after injection, whereas AFL-g was a significant metabolite after 18 hr. This study shows that in vivo administration of AFB1 to zebrafish results in moderate adduction of the carcinogen to liver DNA and that zebrafish have the capacity for both phase I and phase II metabolism of AFB1. The approximate fourfold difference between rainbow trout and zebrafish AFB1-DNA covalent binding index appears insufficient to explain the relative resistance of zebrafish to dietary AFB1 hepatocarcinogenicity.
Subject(s)
Aflatoxin B1/metabolism , Carcinogens/metabolism , DNA Adducts/metabolism , Liver/metabolism , Zebrafish/metabolism , Aflatoxin B1/toxicity , Animals , Biological Assay , Carcinogens/toxicity , DNA Adducts/drug effects , Dose-Response Relationship, Drug , Female , Immunity, Innate , Liver/drug effects , Male , Neoplasms, Experimental/chemically induced , Neoplasms, Experimental/physiopathology , Oncorhynchus mykiss/metabolism , Species SpecificityABSTRACT
DMP 323 is a potent inhibitor of the protease of human immunodeficiency virus (HIV), with antiviral activity against both HIV type 1 and HIV type 2. This compound is representative of a class of small, novel, nonpeptide cyclic urea inhibitors of HIV protease that were designed on the basis of three-dimensional structural information and three-dimensional database searching. We report here studies of the kinetics of DMP 323 inhibition of the cleavage of peptide and HIV-1 gag polyprotein substrates. DMP 323 acts as a rapidly binding, competitive inhibitor of HIV protease. DMP 323 is as potent against both peptide and viral polyprotein substrates as A-80987, Q8024, and Ro-31-8959, which are among the most potent inhibitors of HIV protease described in the literature to date. Incubation with human plasma or serum did not decrease the effective potency of DMP 323 for HIV protease, suggesting that plasma protein binding is of a low affinity relative to that of HIV protease. DMP 323 was also assessed for its ability to inhibit the mammalian proteases renin, pepsin, cathepsin D, cathepsin G, and chymotrypsin. No inhibition of greater than 12% was observed for any of these enzymes at concentrations of DMP 323 that were 350 to 40,000 times higher than that required to inhibit the viral protease 50%.
Subject(s)
HIV Protease Inhibitors/pharmacology , Urea/analogs & derivatives , Amino Acid Sequence , Aspartic Acid Endopeptidases/antagonists & inhibitors , Azepines , Blood , Chymotrypsin/antagonists & inhibitors , HIV Protease/analysis , HIV Protease/isolation & purification , HIV-1/enzymology , HIV-2/enzymology , Humans , Kinetics , Molecular Sequence Data , Substrate Specificity , Urea/pharmacologyABSTRACT
The monohydroxyeicosanoid 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), which is derived from oxygenation of arachidonic acid by 12-lipoxygenase, is one of the major metabolites in platelets. In a recent study, we have showed that this eicosanoid stimulated basal sickle-red-cell-endothelial-cell adhesion. To understand the pathophysiologic significance of 12-HETE, we measured the levels of this eicosanoid in plasma and urine from children with sickle cell disease. We found that as compared with controls, plasma 12-HETE levels are increased in patients with sickle-cell disease in the steady state, and are increased further during vaso-occlusive crises. Urinary 12-HETE levels were also increased during the steady state. We also assessed plasma levels of soluble P-selectin (another potential marker for platelet activation), and found changes in the levels of this marker similar to those seen with plasma 12-HETE. In additional studies, we found that 12-HETE enhanced hypoxia-induced sickle-red-cell-endothelial adherence, and that this effect was mediated by potentiation of agonist-induced upregulation of the expression of the mRNA for vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells. Because 12-HETE appears to enhance both basal and agonist-induced sickle-red-cell adhesion, this metabolite could potentially play a role in the pathogenesis of the vaso-occlusive crisis (VOC) in sickle-cell disease.
Subject(s)
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/physiology , Anemia, Sickle Cell/physiopathology , Arterial Occlusive Diseases/physiopathology , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/blood , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/urine , Adolescent , Adult , Anemia, Sickle Cell/blood , Anemia, Sickle Cell/urine , Animals , Arterial Occlusive Diseases/blood , Arterial Occlusive Diseases/urine , Cattle , Cell Adhesion , Child , Child, Preschool , Endothelium, Vascular/pathology , Gene Expression Regulation/physiology , Humans , Middle Aged , P-Selectin/blood , RNA, Messenger/genetics , Vascular Cell Adhesion Molecule-1/geneticsABSTRACT
Three methods were used in succession to screen a whole adult zebrafish cDNA library for expressed p53-like genes. The sequences of the resultant clones describe an open reading frame 1122 nucleotides in length, with another 43 and 940 bases of 5' and 3' untranslated sequence, respectively. The deduced amino acid sequence of the zebrafish p53 protein is 63% identical to that of trout and 48% identical to that of human p53. Two of the three zebrafish clones overlap to span the entire reported cDNA sequence and are identical in their deduced amino acid sequence over their coincident length. The third clone contains a conservative amino acid change, as well as an inserted amino acid subsequently found to be at the junction of exons 2 and 3, suggestive of alternative splicing in the p53 mRNA for this species. Northern analysis demonstrated a zebrafish p53-related transcript to be present and most abundant in zygotes and early-cleavage embryos less than 1 hour after fertilization, thereafter declining to barely detectable levels at 48 hours. A similar temporal expression was detected for the zebrafish L-myc, known to be present in maternally derived RNA, whereas zebrafish N-myc and the zebrafish homologue of the murine T gene were not detectable prior to the onset of zygotic transcription.