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PubMed2003

Long-term potentiation and long-term depression induced by local application of ATP to hippocampal CA1 neurons of the guinea pig.

The present study has investigated the role of ATP in the induction of synaptic plasticity, using local application of ATP by picopump administration into the stratum radiatum of guinea pig hippocampal region CA1. Excitatory postsynaptic currents (EPSCs) evoked by stimulation of Schaffer collateral/commissural afferents synapsing on CA1 pyramidal cells of hippocampal slices were monitored in voltage-clamp mode, using whole-cell recording. Brief local application of ATP (1 mM) induced an inward current, usually consisting of early- and late-phase components. Because the late-phase component of an ATP-induced current was largely inhibited by Ca2+-free solution, this component is supposed to depend on extracellular Ca2+. After local application of ATP, long-term synaptic modification of EPSCs was induced: LTP was detected in neurons exhibiting a small late Ca2+ current, while LTD was obtained from recordings showing a large late Ca2+ current in response to ATP application. There was a statistically significant correlation between the magnitude of long-term plastic changes and the size of Ca2+ currents in response to ATP application. Furthermore, there was significant difference between the average size of the Ca2+ current in the LTP group and the size in the LTD group. These results suggest that a small Ca2+ influx in response to ATP application induces LTP, whereas a large one induces LTD in guinea pig hippocampal CA1 neurons.

Adenosine Triphosphate↗

PubMed1989

Ingredients of a successful grant application to the National Institutes of Health.

Many factors determine the scientific merit of an NIH research grant application. This paper is intended to help optimize the organization and logical development of investigators' research ideas so that grant applications will be evaluated by the reviewers in as favorable a light as possible. The ingredients of a successful grant application are good ideas, good science, and a good application. The research should be based on a significant hypothesis and, if possible, oriented towards uncovering an important biological mechanism. Specific methods should be directly related to each aim of the project. Likewise, the specific aims should be related to each hypothesis. All aspects of the application should be clear and focused. It is best to define all assumptions, limitations, and alternative approaches. In general, the best philosophy is for the applicant to address all possible problems before the reviewers.

National Institutes of Health (U.S.)↗

PubMed1986

Surgical aptitude test for otolaryngology-head and neck surgery resident applicants.

The search for a convenient, rapid manual dexterity examination, which could be used at the time of the otolaryngology resident applicant's interview, led us to assess the following areas: purposeful hand direction, depth perception, tactile discrimination, finger pressure coordination, finger visual tracking of moving objects, spatial visualization, finger strength, speed of movements, fine control precision, finger dexterity, steadiness during movement, steadiness without movement, and neatness. With the astronomical increase in applicants to a limited number of positions in the field of otolaryngology-head and neck surgery, the application of an accurate, efficient manual dexterity assessment at the time of applicant interview is desirable. Presently, dental school applicants are screened by a series of manual dexterity tests. To develop our screening test, we integrated manual performance tests currently in use by private industry, occupational therapists, and dental school admission committees. Thus, applicants who are able to master fine microsurgical and macrosurgical techniques common in our specialty will be preferentially selected.

Aptitude Tests↗

PubMed2003

Comparison of thermal tissue effects induced by contact application of fiber guided laser systems.

BACKGROUND AND OBJECTIVES: Laser light of various wavelengths is being used for surgical procedures in otolaryngology. Apart from well-known fiber guided laser systems such as Nd:YAG- and Ho:YAG-lasers, newly developed diode-laser systems of different wavelengths have recently become popular in surgery. In order to compare the effects of fiber guided laser light with respect to their induced tissue effects, these laser systems have been studied and compared under reproducible test conditions. STUDY DESIGN/MATERIALS AND METHODS: The laser fibers of four common medical laser systems (Ho:YAG- (lambda = 2,080 nm), Nd:YAG- (lambda = 1,064 nm), and diode-laser (lambda = 830 and 940 nm)) were fixed to a computer controlled stepper motor. The laser light was applied in contact mode onto ex vivo muscle tissue, using identical power settings and a reproducible application procedure (application velocity, application angle) under constant conditions (temperature of tissue and volume). The size of the thermal effects on the tissue (e.g., coagulation, ablation, and carbonization zones) were measured and photographed via optical microscopy. RESULTS: Depending on the laser wavelength used, the experimental results proved different degrees of tissue responses. Nd:YAG- and diode-lasers provided for only low coagulation effects in the depth of the tissue, but produced severe carbonization at the surface. Ho:YAG-laser light revealed the highest ablation capabilities of the lasers investigated in addition to large coagulation zones which were of larger extent than those produced by Nd:YAG- and diode-laser light. CONCLUSIONS: Contact treatment by Ho:YAG-laser light might provide for a precise and effective tissue reduction in a bloodless manner because of its high ablation and coagulation capabilities, especially if large volumes are treated and structures beneath are non-critical. In comparison, Nd:YAG- and diode-laser treatment in contact application showed low thermal tissue effects (i.e., coagulation) in the depth, resulting from a high power loss caused by the development of large carbonization zones at the surface of the tissue. Therefore, the degree of blood-perfusion and the capability of vessel-closure induced by these lasers should be taken into account. The presented investigation also revealed that in contact mode, the tested laser systems produced tissue effects, which were highly different from those already described for applications in non-contact mode. Physicians who are performing laser treatments in close boundaries must be aware that changing from non-contact to contact mode in laser application greatly influences the resulting tissue effects.

Animals↗

PubMed2002

Assessment of relevant factors and relationships concerning human dermal exposure to pesticides in greenhouse applications.

Principal component analysis (PCA) was applied to the gas chromatographic data obtained from 23 different greenhouse trials. This was used to establish which factors, including application technique (very small, small, medium and large drop-size), crop characteristics (short/tall, thin/dense) and pattern application of the operator (walking towards or away from the treated area) are relevant to the dermal exposure levels of greenhouse applicators. The results showed that the highest exposure by pesticides during field applications in greenhouses, in the climatic conditions and in the crop conditions typical of a southern European country, occurs on the lower legs and front thighs of the applicators. Similar results were obtained by hierarchical cluster analysis (HCA). Drop-size seems to be very important in determining total exposure, while height and density of crops have little influence on total exposure under the conditions of the present study. No pesticide type is a major factor in total exposure. The application of multiple regression analysis (MRA) allowed assessment of the relationships between the pesticide exposure of the less affected parts of the body with the most affected parts.

Agriculture↗

PubMed1999

Evaluation of spinning disc technology for the application of entomopathogenic nematodes against a foliar pest.

Two spinning disc spray application systems, the Micron Herbaflex and Micron Ulva+, were assessed for their potential for the application of infective juveniles (IJs) of entomopathogenic nematodes (EPNs) against larvae of the diamondback moth (DBM), Plutella xylostella. The effect of initial concentration of IJs on subsequent infection was examined for three species of EPNs: Steinernema sp. (M87), Steinernema sp. (SSL85), and Heterorhabditis sp. Increasing the concentration of IJs generally resulted in a significant increase in both DBM mortality and the mean number of nematodes per larva following spray application with the Micron Herbaflex sprayer. Application with the Micron Ulva+ was examined using two different initial concentration of IJs, which generally resulted in an increase in DBM mortality and intensity of infection. The effect of changing the flow rate to the Ulva+ was also examined. This generally resulted in increased DBM mortality as flow rate was increased but there was little change in the mean number of nematodes per host larva. The effect of addition of a number of adjuvants to the spray solution on subsequent infection showed that DBM mortality by the IJs was not significantly affected but that the mean number of nematodes infecting was significantly enhanced by some of the adjuvants. Desiccation survival studies with IJs of Heterorhabditis sp. following application with both sprayers onto Chinese cabbage leaf discs, with or without the addition of an adjuvant, showed that the survival time of 50% of IJs was over 3 h. Infection of DBM larvae was also assessed following desiccation on Chinese cabbage leaf discs. High levels of infection were attainable, in terms of resultant DBM mortality, for at least 150 min following spray application.

Animals↗

PubMed2001

Properties, modifications and applications of biopolyesters.

Poly(hydroxyalkanoates) (PHAs), of which poly(hydroxybutyrate) (PHB) is the most common, can be accumulated by a large number of bacteria as energy and carbon reserve. Due to their biodegradability and biocompatibility these optically active biopolyesters may find industrial applications. A general overview of the physical and material properties of PHAs, alongside with accomplished applications and new developments in this field is presented in this chapter. The properties of PHAs are dependent on their monomer composition and therefore it is of great interest that recent research has revealed that, in addition to PHB, a large variety of PHAs can be synthesized microbially. The monomer composition of PHAs depends on the nature of the carbon source and microorganism used. PHB is a typical highly crystalline thermoplastic whereas medium chain length PHAs are elastomers with low melting points and a relatively lower degree of crystallinity. By (chemical) modification of the PHAs, the ultimate properties of the materials can be adjusted even further, when necessary. Applications that have been developed from PHB and related materials (e.g. Biopol) can be found in very different application areas and cover packaging, hygienic, agricultural and biomedical products. Recent application developments based on medium chain length PHAs range from high solid alkyd-like paints to pressure sensitive adhesives, biodegradable cheese coatings and biodegradable rubbers. Technically, the prospects for PHAs are very promising. When the price of these materials can be further reduced, application of biopolyesters will also become economically very attractive.

Bacteria↗

PubMed1989

Effect of continuous vs intermittent application of 3-OH-tamoxifen or tamoxifen on the proliferation of the human breast cancer cell line MCF-7 M1.

The antiproliferative potency of 5 x 10(-7) M tamoxifen (TAM) and 3-hydroxytamoxifen (3-OH-TAM) was investigated during continuous (8 days) or intermittent (2 h every 2nd or 3rd day, respectively) application to the oestrogen-receptor-positive, estradiol-sensitive human mammary carcinoma cell line MCF-7 M1, a variant of MCF-7 wild type. Growth modulation was evaluated in parallel by counting cells and by measuring DNA content. Continuous incubation resulted in a growth inhibition to 21.8 +/- 3.2% by 3-OH-TAM and to 39.5 +/- 4.8% by TAM when compared with control cultures defined as 100%. Intermittent addition induced a growth reduction to 23.0 +/- 2.1% by 3-OH-TAM and to 41.2 +/- 2.4% by TAM in relation to 100% controls. Addition of 3-OH-TAM for 2 h only at day 1 resulted in an inhibition to 70.3 +/- 3.2%, again in relation to 100% controls. When TAM was administered once for 2 h at day 1 it induced an inhibition to 79.0 +/- 4.9% at day 8. The in vitro results indicate that (a) at 5 x 10(-7) M 3-OH-TAM has a better antiproliferative effectiveness than TAM, (b) the intermittent application is as effective as continuous application (no significant difference), and (c) the addition once a week reveals only a slight growth reduction after 8 days of culture. Application of the long-living TAM results in continuously high serum concentrations, which have been shown to create resistant cell clones. Compared to TAM the 3-OH metabolite has a considerably shorter half-life and its application in vivo reveals rise and fall of its serum concentrations. Since the presented data demonstrate that 3-OH-TAM is more potent than TAM and that the intermittent application is as effective as the continuous form, interval therapy with 3-OH-TAM may slow down the process of acquiring resistance to antioestrogens.

Breast Neoplasms↗

PubMed1993

[A FEM study for the biomechanical comparison of labial and palatal force application on the upper incisors. Finite element method].

The present study was designed to compare the biomechanical response of upper incisors to labial and lingual force applications. A three-dimensional finite element model was developed to analyze tooth displacement and stress distribution in the periodontal ligament. Lingually and apically directed forces of 1 N were applied at one point on the labial and at three points on the lingual surface of the crown. Tooth displacement and stress distribution resulting from lingual force applications were compared with those from the labial side. The following results were obtained: 1. Lingual horizontal forces produced similar patterns of tooth displacement and stress distribution, irrespective of the point of application (labial--lingual). 2. Apically directed vertical forces applied at the lingual points produced more uniform tooth displacements and stress distributions, although the force applied on the lingual side close to the CEJ, which happened to be most distant from the tooth's long axis, generated a pattern of movement somewhat different from the remaining two lingual force applications. The present results suggest the crucial role of the positional relation between the long axis of the tooth, respectively the center of resistance, and the point of force application. It can be deduced that lingual force application may produce more optimal tooth movement in terms of intrusion and subsequent stress distributions in the periodontal ligament.

Biomechanical Phenomena↗

PubMed1981

Control of microorganisms in the rhizosphere of wheat by inoculation of seeds with Pseudomonas putida and by foliar application of urea.

After inoculation of wheat seeds with various bacterial strains germination of plants was usually inhibited at first but growth was stimulated later. After inoculation with Pseudomonas putida K 11 producing physiologically active compounds the total number of bacteria increased together with the bacteria: fungi ratio in the rhizosphere. These characteristic were further increased after foliar application of urea due to increased root exudation. Dry mass of upper wheat parts was about 14--80% higher in green-house experiments, in which the plants were treated in the two above ways. More reliable results were usually obtained by bacterization of P. putida and foliar application of urea as compared with the situation when the seeds were inoculated without the foliar application or, on the contrary, after foliar application without inoculation of the seeds. Only when urea was applied early and ain a soil contaminated with the fungus Gaeumannomyces graminis var. tritici (causing "take-all" of the wheat) no favourable results could be detected. In these cases the foliar application without inoculation of the seeds was more successful. Symptoms of the disease of wheat roots caused by G. graminis were less frequently observed after the inoculation of the seeds with the strain P. putida K 11 and after the foliar application of urea.

Ecology↗

PubMed2006

Effects of application methods of metam sodium and plastic covers on horizontal and vertical distributions of methyl isothiocyanate in bedded field plots.

This study was conducted to examine the effects of three application methods of metam sodium (broadcast, single irrigation drip tape delivery, and double irrigation drip tape delivery) and two plastic covers (polyethylene film and virtually impermeable film) on volatilization and on horizontal and vertical distributions of the biologically active product of metam sodium, methyl isothiocyanate (MITC), in field plots in a Florida sandy soil. Volatilization of MITC from field beds lasted for about 20 hours after completion of metam sodium application regardless of application methods. Virtually impermeable film (VIF) was a better barrier to reduce volatilization loss than polyethylene film (PE). Since water was not applied during broadcast application, MITC was mainly retained in the shallow soil layer (0- to 20-cm depth) and downward movement of MITC was limited to about 30 cm. Large values of standard deviation indicated that initial spatial distribution of MITC in the root zone (10- and 20-cm depths) of the two broadcast applied beds covered with PE or VIF was variable. Twice more water was delivered through the single drip tape than through individual tapes of double drip tape treatments during drip application of metam sodium. More water from the single drip tape likely facilitated downward movement of MITC to at least 60-cm depth, but MITC did not penetrate to this depth in the double drip tape beds. On the other hand, horizontal distribution of MITC in the root zone (10- and 20-cm depths) in the double drip tape beds was more uniform than in the single drip tape beds. More MITC was retained in the subsurface of the VIF-covered beds regardless of application methods than in the PE-covered beds.

Agriculture↗

PubMed2001

Long-term fate of glyphosate associated with repeated rodeo applications to control smooth cordgrass (Spartina alterniflora) in Willapa Bay, Washington.

Cordgrasses (Spartina sp.) are exotic, invasive species that threaten to degrade the intertidal zones of estuaries along the West Coast of North America. Integrated pest management (IPM) strategies primarily focus on the use of aerial and ground applications of Rodeo in conjunction with mowing, but IPM treatments over multiple years usually are necessary to control Spartina. Although information exists regarding the short-term fate and effects to marine biota of a single Rodeo application to control Spartina, little information is available regarding the fate and biotic effects associated with repeated Rodeo applications necessary for control. Consequently, we conducted a 3-year study to assess the short- and long-term fate and potential effects to marine biota associated with repeated applications of Rodeo to control smooth cordgrass in a southwestern Washington estuary. At each of three intertidal locations in Willapa Bay, we established plots on exposed mudflats and along the edge of a Spartina meadow that were hand sprayed with Rodeo (5% solution) and LI-700 (2% solution) during July 1997 and 1998. Glyphosate concentrations in sediment from mudflat plots declined 88% to 96% from 1 day posttreatment in 1997 to 1 year after the second Rodeo applications in 1999. In contrast, glyphosate concentrations in Spartina plots increased 231% to 591% from 1997 to 1999 because Spartina rhizomes likely did not readily metabolize or exude it. Comparison of concentrations from mudflat and Spartina plots with toxicity test values for marine biota indicates that under worst-case conditions short- and long-term detrimental effects to aquatic biota from repeated application of Rodeo for Spartina control would be highly unlikely.

Glycine↗

PubMed1998

Repeated application of carvone-induced bacteria to enhance biodegradation of polychlorinated biphenyls in soil.

Carvone, the principal component of spearmint oil, induces biodegradation of polychlorinated biphenyls (PCB) by Arthrobacter sp. strain B1B. This study investigated the effectiveness of the repeated application of carvone-induced bacteria for bioremediation of Aroclor-1242-contaminated soil. Control treatments compared a single inoculation of carvone-induced cells, repeated applications of noninduced cells, and repeated applications of cell-free carvone/fructose medium. The results showed that repeated application of carvone-induced bacteria was the most effective treatment for mineralizing PCB, resulting in 27 +/- 6% degradation of Aroclor 1242 after 9 weeks; whereas a single application of cells resulted in no significant degradation. Addition of cell-free, carvone/fructose medium resulted in 10% degradation of PCB, which suggests that this treatment stimulated biodegradation of PCB by the indigenous microflora. The di- and trichlorobiphenyls were the most readily degraded congeners. More highly chlorinated congeners, which had been previously shown to be degraded in liquid culture, were not substantially degraded in soil, indicating that low bioavailability may have limited their degradation. With the development of new technology, which permits automated in situ fermentation and delivery of degrader microorganisms, the repeated application of carvone-induced bacteria may facilitate bioremediation of PCB-contaminated soils.

Aroclors↗

PubMed2005

Formalin application in the treatment of chronic radiation-induced hemorrhagic proctitis--an effective but not risk-free procedure: a prospective study of 33 patients.

PURPOSE: This prospective study evaluated the efficacy and safety of local formalin application in chronic refractory radiation-induced hemorrhagic proctitis. METHODS: All patients were treated under anesthesia by direct application of 4 percent formalin to the affected rectal areas. RESULTS: The study included 33 patients (17 women) and was conducted between January 1994 and December 2001. There were 11 anal cancers (33 percent), 11 prostate cancers, 9 cervical or endometrial cancers, 1 bladder cancer, and 1 rectal cancer. The mean number of daily rectal bleeds was 2.7 (range, 0.5-15). Nineteen patients (58 percent) were blood transfusion dependent. Twenty-three patients had only one formalin application and 10 patients required a second application because of the persistent bleeding. The treatment was effective in 23 cases (70 percent): 13 patients had complete cessation of bleeding and 10 patients had only minor bleeding. Six anal or rectal strictures occurred: 4 patients had been treated for anal cancer (36 percent) and 2 patients had been treated for other cancers (9 percent). None of the strictures was malignant. Anal incontinence worsened in 5 patients of the 11 who had been treated for anal cancer (45 percent) and occurred in 4 of the 22 other patients (18 percent). CONCLUSION: Formalin application is an effective treatment for chronic radiation-induced hemorrhagic proctitis. However, local morbidity is not negligible. This result may be related to the high proportion of anal cancers in the series. In our opinion, therefore, formalin application should be reserved for severe hemorrhagic proctitis refractory to medical treatment and should be thoroughly discussed in cases of anorectal radiation-induced stricture, prior anal incontinence, or treated anal cancer.

Aged↗

PubMed1990

Myometrial activity after local application of prostaglandin E2 for cervical ripening and term labor induction.

Twelve pregnant women at term with unfavorable cervices (less than or equal to 5 points according to Bishop score) were given prostaglandin E2 for cervical priming and labor induction. Prostaglandin E2 was given in the following manner: 0.5 mg in gel strictly intracervically (n = 4), extraamniotically (n = 4), or prostaglandin E2 (4 mg) in gel vaginally (n = 4). The myometrial activity was registered over a period of 30 minutes before and at least 3 hours after gel application by means of an extraamniotic microtransducer catheter. After both extraamniotic and vaginal gel application, myometrial activity was significantly increased compared with intracervical application. All the women had favorable cervical states 6 hours after treatment and were delivered vaginally within 24 hours. All infants were delivered in good condition with 1-minute Apgar scores greater than 7. From these results we conclude that proper intracervical prostaglandin E2 gel application, in contrast to extraamniotic or vaginal application, induces cervical ripening without significant myometrial activity. Because careful intracervical application appears to avoid or minimize the risks of myometrial hyperstimulation, this technique should be considered particularly in women with unfavorable cervices and delicate fetuses.

Administration, Intravaginal↗

PubMed1992

Golgi-like staining of visual cortex cells obtained by extracellular biocytin application in vitro.

We report here the application of biocytin (a biotin-lysine complex) as an extracellular tracer in vitro. Biocytin was applied extracellularly, revealing Golgi-like staining of cells in the adult in vitro rat visual cortex. Micropipettes were filled with a solution of 2.3-2.6% biocytin dissolved in 0.05 M Tris buffer, pH 7.4. Biocytin was applied by one of 3 methods: diffusion, pressure injection or drop application. Cell bodies and dendrites around the application site and their efferent axonal processes were stained; dendritic spines were often visible. The injection sites varied in size from a single cell to a diameter of 400 microns. When applied in layer I-III, few filled cells were also seen in layers IV and V, outside the application site. The drop application (5-10 microliters) of biocytin resulted in filling of cells throughout the cortex. The combination of biocytin and the slice preparation was found to be very useful in revealing cell morphology and tracing interlaminar connections in the visual cortex. The advantages of this technique are its ease of application, the precise and restricted injection sites, and Golgi-like morphological detail.

Animals↗

PubMed1996

Local pressure application of cannabinoid agonists increases spontaneous activity of rat substantia nigra pars reticulata neurons without affecting response to iontophoretically-applied GABA.

This study tested the hypothesis that cannabinoid agonists, applied locally into the pars reticulata of substantia nigra (SNpr), could modulate striatonigral transmission, without affecting the response of SNpr neurons to iontophoretically-applied GABA. Multibarreled glass capillary electrode assemblies were used for extracellular recording of the spontaneous electrical activity of single SNpr cells in anesthetized rats. Local pressure ejection of the cannabinoid agonists Win 55212-2 (WIN2) and CP 55940 increased SNpr spontaneous firing rate by 13-46%, similar to the effects of systemic injections. Neither WIN2 nor CP 55940 had an effect on the slowing of SNpr neuron activity in response to iontophoretic GABA. Local pressure application of Win 55212-3 (the much less active enantiomer of WIN2) produced an insignificant decrease in SNpr firing rate. Similarly, locally applied vehicle (45% 2-hydroxypropyl-beta-cyclodextrin) produced insignificant decreases in SNpr firing. A second application of cannabinoid agonist produced a much smaller effect, suggesting desensitization. Increasing the interval between CP 55940 applications to 45 min showed recovery of sensitivity to the agonist. Local application of the cannabinoid antagonist, SR 141716A, significantly decreased spontaneous cell firing by 34%. CP 55940, when given immediately following or concurrently with the antagonist application failed to produce the expected increase in discharge rate over baseline. A second application of CP 55940 45 min later produced a 26% increase in firing rate. Bicuculline methiodide (BMI) was applied locally causing a significant increase in SNpr cell firing. CP 55940, when locally administered concurrently with bicuculline methiodide, had no further effect on the firing rate of the cell. Based on the reported presynaptic localization of cannabinoid receptors in SNpr, these findings suggest that cannabinoids act within the SNpr to modulate striatonigral neurotransmission presynaptically. The effect of SR 141716A suggests that an endogenous cannabinoid may mediate striato-nigral transmission.

Action Potentials↗

PubMed1984

Systemic effects of topical application of T-2 toxin in mice.

Topical application of T-2 toxin in dimethyl sulfoxide (DMSO) resulted in the death of 20/20 mice in the 20-, 30-, and 40-mg/kg body weight (BW) dose groups within 4 to 6 days after application, whereas 17/20 and 5/20 animals died in the 10- and 5 mg/kg BW groups, respectively, within 7 days. Histological examination of thymus, spleen, and duodenum at 6, 12, 18, and 24 hr after topical application of 5 or 40 mg/kg BW to mice revealed that the characteristic radiomimetic effects of this trichothecene mycotoxin are easily recognizable at 6 hr after topical application, with the severity of damage being dependent on the organ and time. The lesions are quantitatively and qualitatively identical with those seen after intragastrical application of T-2 toxin. Both the postmortem and, to some extent, the general histological findings were not specific enough to arrive at an etiological diagnosis without prior knowledge of the fact that a mycotoxin was applied to the skin, unless one had the opportunity to look for the characteristic intestinal lesions prior to 24 hr after application, or for necrosis in spleen an thymus after 24 hr.

Animals↗