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[Experimental studies on tissue distribution of 14C-labelled antimicrobial agent in the otorhinolaryngological field--application of macro-autoradiography].

The distribution of antimicrobial agents in infected target tissues would be essential for their application to treat the sites of infection. Taking accounts of the view point, we had reported the distribution of 3 nalidixic acid analogs in tissues which are related to otorhinolaryngology by macro-autoradiography and radiometry. We investigated here in the distribution of a nalidixic acid analog OPC-7241. This agent is 9-fluro-5-methyl-8-(4-methyl-1-piperaginyl)-6, 7-dihydro-1-oxo-1H, 5H-benzo [ij]quinoligine-2-carboxylic acid supplied by Otsuka Pharmaceutical Co., Ltd. Autoradiography was performed 30 minutes after intravenous administration of 14C-OPC-7241 in 2.96 MBq(80.0 microCi)/12.5mg/kg to New Zieland White rabbit. Radiometry was performed 30 minutes, 1 hour and 3 hours after intravenous administration of 14C-OPC-7241 in 740 kBq (20.0 microCi)/10.0 mg/kg to NZW rabbits. Such care was taken in filling the carboxymethyl cellulose paste into the paranasal cavity, nasal cavity, oral cavity and external ear canal not to damage mechanically. Horizontal frozen sections parallel to mandibular basis were cut in 50 microns thickness in a cryostadt. Blackening of 14C-OPC-7241 was most significant in soft palate and its expanse which is apparently the same gland-like tissues as soft palate when stained with hematoxylin and eosin. Significant radioactivity was recognized in tonsils, the cartilage of external ear canal, septal cartilage, periodontal membrane, dental pulp, muscle and concha nasalis ventralis. The levels was low in ethmoid cells, mucosa of tympanic cavity, cochlea, maxillary sinus and bone. Quantitatively, the levels of 14C-OPC-7241 radioactivity were high in soft palate, mandibular gland and tonsils. Radioactivity was significant in tongue and concha nasalis ventralis. The levels were low in turbinates, ethmoid cells, maxillary sinus, septal cartilage, septal mucosa, cochlea, brain, optic nerve and lens. Thus radiometric results agreed with the above autoradiographic findings. Macro-autoradiography can be one of useful means for the evaluation chemotherapeutic agents for possible clinical application.

Animals↗

Thermal and chemical modification of dentin by 9-11-microm CO2 laser pulses of 5-100-micros duration.

BACKGROUND AND OBJECTIVES: Previous studies have shown that dentin can be thermally modified by pulsed CO(2) laser irradiation to form a more highly mineralized tissue. The implications are important for the potential laser modification or removal of dentinal and root caries and the transformation of dentin to a more acid resistant mineralized tissue. STUDY DESIGN/MATERIALS AND METHODS: Time resolved radiometry measurements with TEA CO(2) laser pulses were used to determine the magnitude of the absorption coefficients of dentin at the highly absorbed CO(2) laser wavelengths and to measure the temperature excursions during lambda = 9.3, 9.6, 10.3, and 10.6 microm laser irradiation at irradiation intensities of 0.1-8 J/cm(2) per pulse. In addition, photoacoustic and transient reflectance measurements were used to monitor the loss of water and organics and to detect the thresholds for surface modification and tissue ablation. RESULTS: The absorption coefficients were measured to be 5,000; 6,500; 1,200; and 800 cm(-1) at lambda = 9.3, 9.6, 10.3, and 10.6 microm, respectively. The surface temperatures of dentin were markedly higher than those measured on enamel for similar irradiation intensities due to the lower reflectance losses of dentin and the lower thermal diffusivity of dentin at the respective wavelengths. Hence, lower fluences are required for the thermal decomposition of dentin. Ablation typically occurred with the first few laser-pulses during multiple pulse irradiation and eventually ceased after modification of dentin to a more highly mineralized enamel-like tissue. The debris ejected during the initial laser pulses shielded the surface by as much as 60% at the low fluences employed in this study. Optical and electron microscopy and IR spectroscopy indicated that incident laser pulses with incident fluence as low as 0.5 J/cm(2) at 9.3 and 9.6 microm wavelengths with a duration of 5-8-micros were sufficient to induce chemical and morphological changes in dentin. CONCLUSIONS: In this study, the laser parameters for the efficient thermal modification of dentin with minimum heat deposition at CO(2) laser wavelengths were firmly established.

Dental Caries↗

Silver halide fiber optic radiometric temperature measurement and control of CO2 laser-irradiated tissues and application to tissue welding.

Tissue heating by laser irradiation has attained importance in many clinical applications. Accurate temperature measurements of laser-irradiated tissues are difficult to achieve, and experiments have produced conflicting results. Fiber optic radiometry allows temperature measurement of laser-irradiated tissues by remote sensing of the emitted infra red (IR) radiation. We have developed an IR fiber optic radiometer capable of accurate tissue temperature measurements (+/- 0.2 degrees C) and utilized it to monitor and control the heating of tissues by CO2 laser irradiation. Tissue temperature control of +/- 2.5 degrees C was achieved. This system was used to control tissue temperature during CO2 laser-assisted welding of urinary bladders in rats. The strength of the welds was recorded for different welding temperatures. A temperature of 55 degrees C was found to be optimal.

Animals↗

Origin and renewal of the intrinsic glycoproteins of the aqueous humor.

Rabbits were injected either intravitreally or intra-aqueously with L-[3H]-fucose and killed at several intervals after the administration of this marker for glycoproteins. The aqueous humor, the vitreous body and the ciliary body were processed for radiometry (liquid scintillation counting), sodium dodecyl sulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and fluorography. Light microscopic autoradiography was carried out on semi-thin sections of the ciliary body and revealed intense activity in terms of the synthesis, migration and renewal of glycoproteins in the ciliary epithelium. The amount of unbound [3H]-fucose in the aqueous humor decreased sharply by 4 h, and the labeled glycoproteins were present only in very small quantities at 1 day after the intra-aqueous injection. When [3H]-fucose was injected intravitreally, unbound radiolabel could be detected in the aqueous humor for greater than 1 day and the labeled glycoproteins, for up to 21 days after injection. The amount of unbound or bound [3H]-fucose was higher in the vitreous than in the aqueous at any interval after the intravitreal injection. Following the intra-aqueous injection, the amount of label that reached the vitreous body was practically insignificant. The levels of radioactivity in the serum were extremely low, as they were in the contralateral eye when tritiated fucose was injected into one eye only. Most of the Coomassie blue-stained bands detected in SDS-PAGE contained labeled glycoproteins as revealed by fluorography of gels simultaneously containing aqueous and vitreous samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Experimental investigation of the mammary gland tumour phantom for multifrequency microwave radio-thermometers.

Microwave radiometry is a spectral measurement technique for resolving the electromagnetic radiation of matter when its temperature is above absolute zero. The radio-thermometer utilises this technique and consequently can provide temperature distributions in subcutaneous biological tissues. A new phantom was proposed that imitates a mammary gland tumour, and the brightness temperature was observed using radio-thermometers operated at different frequencies, 1.75GHz and 3GHz. The proposed phantom, simulating heat diffusion propagated by tissues around real tumours, revealed that the thermal characteristics of the tumour imitator were well matched to the heat transfer properties of a real tumour and a proportional linear relationship between the location of the tumour imitator and the brightness temperature in a homogenous medium was established. From experiments using the proposed mammary gland tumour phantom and a clinical trial on patients with breast cancer, it could be concluded that a radio-thermometer with a short wavelength (lambda = 10cm, i.e. f= 3GHz) is useful to resolve a thermal anomaly at a shallow depth in an homogenous medium such as a breast.

Adult↗

Automated methods for detection of bacteriuria.

Urine specimens represent a large portion of cultures received by the clinical microbiology laboratory. Much time and effort are spent screening these specimens and approximately 80 percent show no growth. The methods employed for detection of bacteriuria include microscopic, chemical, culture, and automated. The most widely used procedure has been an agar plate culture method. However, this method requires overnight incubation and therefore results are delayed. Within the last decade many automated methods have been introduced for detecting bacteriuria, and results are available more rapidly than with the agar plate culture method. In addition to decreased detection time, these systems are accurate and cost-effective. The purpose of this report is to review these automated bacteriuria screening systems, which include bioluminescence, colorimetry, electrochemical screening, electrical impedance, microcalorimetry, photometry, and radiometry. Accuracy, detection time, and cost are also discussed in this review.

Adenosine Triphosphate↗

Direct measurement and regulation of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) generation in vitro.

3'-Phosphoadenosine 5'-phospho[35S]sulfate (PAPS) biosynthesized from inorganic [35S]sulfate and ATP was separated from its radiolabeled precursor by reversed-phase paired-ion HPLC and quantified by on-line radiometric detection. This single-step procedure circumvents several problems inherent in conventional sulfotransferase-coupled assays employed in the measurement of PAPS formation. A good correlation was observed between the rate of PAPS generation assayed in several mammalian tissues measured by direct HPLC-radiometry and by coupling to the sulfation of minoxidil or 4-methylumbelliferone. Both AMP and ADP inhibited the rat liver sulfate-activating enzymes competitively with respect to MgATP2-, and the rate of PAPS production was decreased with decreasing ratios of [ATP]:[ADP] and [ATP]:[AMP]. It is possible that these adenine nucleotides regulate sulfate activation by kinetic control and by negative feedback modulation.

Adenosine Diphosphate↗

Proposal for a new radiation dose control system for future manned space flights.

Radiation risk on a future long-duration manned space mission appears to be one of the basic factors in planning and designing the mission. Since 1988 different active dosimetric investigations has been performed on board the MIR space station by the Bulgarian-Russian dosimeter-radiometer LIULIN and French tissue-equivalent proportional counters CIRCE and NAUSICAA. A joint French-Bulgarian-Russian dosimetry experiment and the dosimetry-radiometry system RADIUS-MD have been developed for the future MARS-96 mission. On the base of the results and experience of these investigations a conception for a new radiation dose control system for the future orbital stations, lunar bases and interplanetary space ships is proposed. The proposed system which consists of different instruments will allow personal radiation control for crew members, radiation monitoring inside and outside each habitat, analysis and forecasting of the situation and will suggest procedures to minimize the radiation risk.

Cosmic Radiation↗

Space radiation dosimetry with active detections for the scientific program of the second Bulgarian cosmonaut on board the Mir space station.

A dosimetry-radiometry system has been developed at the Space Research Institute of the Bulgarian Academy of Science to measure the fluxes and dose rates on the flight of the second Bulgarian cosmonaut. The dosimetry system is designed for monitoring the different space radiations, such as solar cosmic rays, galactic cosmic rays and trapped particles in the earth radiation belts. The system consists of a battery operated small size detector unit and a "read-write" and telemetry microcomputer unit. The sensitivity of the instrument (3.67 x 10(-8) rad/pulse) permits high resolution measurements of the flux and dose rate along the track of the Mir space station. We report our initial results for the period of the flight between the 7th and 17th June 1988.

Atlantic Ocean↗

"Mir" radiation dosimetry results during the solar proton events in September-October 1989.

Using data from dosimetry-radiometry system "Liulin" on board of "Mir"-space station the particle flux and doserate during September-October, 1989 has been studied. The orbit of the station was 379 km perigee, 410 km apogee and 51.6 degrees inclination. Special attention has been paid to the flux and doserate changes inside the station after intensive solar proton events (SPE) on 29 of September, 1989. The comparison between the doses before and after the solar flares shows increase of the calculated mean dose per day by factor of 10 to 200. During the SPE on the 29 of September the additional dose was 310 mrad. The results of the experiment are compared with the data for the solar proton fluxes obtained on the GOES-7 satellite.

Bulgaria↗

Uptake and elimination of ethanol by young zebrafish embryos.

Among animal models being explored to understand ethanol-induced teratogenesis, the zebrafish (Danio rerio) is attracting attention because its embryonic development is well characterized and readily visualized. Despite the potential of the zebrafish embryo in research on developmental anomalies produced by ethanol exposure, little is known about the relationship between embryonic ethanol content and the nature/severity of ethanol-mediated deficits. Here, using gas chromatography and radiometry of labeled ethanol carbon, we examine accumulation and clearance of ethanol by dechorionated zebrafish embryos during blastulation/gastrulation. Our data indicate that: (a) rates of uptake and loss of ethanol are directly proportional to the extra-/intra-embryonic ethanol concentration gradient and (b) ethanol in the water fraction of embryos reaches near equimolarity with ethanol in the exposure medium. It appears that, within a wide range of exposure concentrations, embryonic ethanol content can be predicted accurately according to exposure time. Furthermore, it appears that embryonic ethanol can be adjusted rapidly to and maintained at a targeted concentration.

Analysis of Variance↗

Measurement of glutamine synthetase activity in rat muscle by a colorimetric assay.

Glutamine synthetase catalyses the formation of L-Gln from L-Glu and NH4+. This enzyme also exerts a glutamyl-transferase activity that produces gamma-glutamyl-hydroxamate from Gln and hydroxylamine. This gamma-glutamyl-transfer reaction can be used to determine glutamine synthetase activity by colorimetric assay. This method has never been applied to rat muscle. The aim of this work was to study and optimize the glutamine synthetase assay conditions in rat muscle. Enzyme activity was linear with time of incubation (30 min at 37 degrees C) and linear with enzyme concentration in the incubation medium. The method was specific. In addition, this assay correlated well with a radiometric assay (y = 0.76x + 340, where x and y are the glutamine synthetase activities measured by radiometry and colorimetry respectively; r = 0.94; P = 0.05). Finally, no glutamine synthetase activity was found in muscles of rats treated with methionine sulfoximine, an inhibitor of glutamine synthetase, and activity dramatically rose in muscles from rats treated with dexamethasone, an activator of glutamine synthetase (in extensor digitorum longus: 2717 +/- 54 nmol/min/g protein in dexamethasone-treated rats versus 1228 +/- 114 nmol/min/g protein in control rats, P < 0.0001). In conclusion, the method presented here is accurate and reliable for measurement of glutamine synthetase activity in muscles.

Animals↗

Analysis of the pre-flight and post-flight calibration procedures performed on the Liulin space radiation dosimeter.

Liulin, a dosimetry-radiometry system, was developed to satisfy the requirements for active flux and dose rate measurements for the flight of the second Bulgarian cosmonaut in 1988. The system consists of a compact battery-operated silicon solid state detector unit and a read/write microcomputer and telemetry unit. We describe the pre-flight calibrations with charged particles, using radioactive sources and accelerated 170 MeV/nucleon proton and alpha particles at the Dubna, Russia cyclotron. We discuss comparisons with data obtained on Mir with the French-built tissue equivalent LET spectrometer NAUSICAA. Lastly, we describe post-flight calibrations performed with 1 GeV/nucleon 56Fe ions at the Brookhaven National Laboratory AGS accelerator, where the instrument was mounted in tandem with several thin position-sensitive silicon detectors behind a stopping target. The silicon detectors provided an energy spectrum for the surviving charged nuclear fragments for which the flux and absorbed dose were recorded by Liulin.

Alpha Particles↗

Application of LC-MS analysis to the characterisation of the in vitro and in vivo metabolite profiles of RGH-1756 in the rat.

RGH-1756, 1-(2-methoxy-phenyl)-4-(4-[4-(6-imidazol[2,1-b] thiazolyl)-phenoxy]-butyl-4-(14)C)-piperazine dimethane is a novel atypical antipsychotic drug candidate of Gedeon Richter Ltd. The metabolic pathways of the compound have been investigated by profiling the metabolites present in plasma, bile, and faeces samples of rats treated with (14)C-RGH-1756. The metabolites formed in vitro by rat liver microsomes have also been analysed. Good separation of the compounds has been achieved by gradient HPLC method on Zorbax/Bonus RP-C18 column. Radiometry and mass spectrometry have been applied to detect and characterise the metabolites. The metabolite formed by oxidative cleavage of the chain at the carbon atom adjacent to the piperazine nitrogen has been identified as the major plasma metabolite. Glucuronide conjugate of hydroxy-RGH-1756 has been found as one of the main metabolites excreted in the bile where the unchanged compound has not been detected.

Animals↗

Quantitation of a novel metalloporphyrin drug in plasma by atomic absorption spectroscopy.

A bioanalytical method to quantify cobalt mesoporphyrin (CoMP), a novel therapeutic agent, in plasma has been developed and validated. The approach involves atomic absorption spectroscopy to determine total cobalt in a sample and a back-calculation of the amount of compound present. Endogenous plasma cobalt concentrations were small ( <0.2 ng/ml(-1) Co in rat plasma) in comparison to the quantitation limit (4.5 ng/ml(-1) Co). The inter-day imprecision of the method was 10.0% relative standard deviation (RSD) and the inter-day bias was +/- 8.0% relative error (RE) over a standard curve range of 4.5- 45.0 ng/ml(-1) Co. Because it quantifies total cobalt, the method cannot differentiate between parent drug and metabolites, but negligible metabolism allows reliable estimates of the actual parent drug concentration. A correlation study between the atomic absorption method and 14C-radiometry demonstrated excellent agreement (r = 0.9868, slope = 1.041 +/- 0.028, intercept = 223.7 +/- 190.0) and further substantiated the accuracy of the methods. Methodology was successfully applied to a pharmacokinetic study of CoMP in rat, with pharmacokinetic parameter estimation. The elimination half-lives, after intra-muscular and subcutaneous administration, were 7.7 and 8.8 days, respectively.

Animals↗

(E)-5-[2-(methoxycarbonyl)ethenyl]cytidine as a chemical actinometer for germicidal UV radiation.

(E)-5-[2-(Methoxycarbonyl)ethenyl]cytidine (S) was examined for use as a chemical actinometer for germicidal UV radiation. Its photoproduct, 3-beta-D-ribofuranosyl-2,7-dioxopyrido[2,3-d]pyrimidine (P), is strongly fluorescent with excitation and emission maxima at 330 and 385 nm, respectively. Experiments were conducted to characterize the dynamic behavior of aqueous solutions of S and P when subjected to UV radiation. UV sources used for these experiments included a low-pressure mercury lamp, a XeBr excimer lamp, and a KrCI excimer lamp; all three sources were mounted in collimating devices to provide incident beams that could be easily and accurately characterized by radiometry. These three sources each yielded essentially monochromatic outputwith characteristic wavelengths of 254, 282, and 222 nm, respectively. At practical concentrations, it was found that the absorbance of the actinometer solution was neither high enough to make the actinometer solutions optically opaque nor low enough to be optically transparent to UV. In addition, the photoproduct displayed a molar absorption coefficient that was similar in magnitude to that of the parent compound, thereby resulting in competitive absorption of UV energy between Sand Pduring irradiation. For purposes of evaluation of the results of irradiation, a mathematical model was developed to accountforthe nonideal optical characteristics of the system. The model is based on a description of local photochemical kinetics; predictions of overall reactor performance were developed by spatial and temporal integration of model results. The model was used to analyze the dynamic behavior of actinometer solutions during UV irradiation and to estimate the quantum yield for photoproduction of Pfrom S. This modeling approach is potentially applicable to other photochemical processes in which multiple compounds are present that absorb photoactive radiation; however, general application of this modeling approach to photochemical reactor systems will require inclusion of othertermsto describe relevanttransport behavior within the system.

Cytidine↗

Microwave radiometric thermometry and its potential applicability to ablative therapy.

INTRODUCTION: [corrected] Current techniques for estimating catheter tip temperature in ablative therapy for cardiac arrhythmias rely on thermocouples or thermistors attached to or embedded in the tip electrode. These methods may reflect the electrode temperature rather than the tissue temperature during electrode cooling so that the highest temperature away from the ablation site may go undetected. A microwave radiometer is capable of detecting microwave radiation as a result of molecular motion. In this study, we evaluated microwave radiometric thermometry as a new technique to monitor temperature away from the electrode tip during ablative therapy utilizing a saline model. METHODS AND RESULTS: A microwave radiometer antenna and fluoroptic thermometer were inserted in a test tube with circulating room temperature saline kept constant at 23.5 degrees C while the surrounding saline bath was heated from 37 degrees C to 70 degrees C. For every degree rise in the warm saline bath placed either 5 mm or 8 mm from the radiometer antenna, the radiometer temperature changed 0.26 degrees C and 0.14 degrees C respectively while the fluoroptic temperature probe remained constant at 23.5 degrees C. The radiometer temperature was highly correlated with the warm saline bath temperature (R(2)=0.997 for warm saline 5 mm from the antenna, R(2)=0.991 for warm saline 8 mm from the antenna). CONCLUSIONS: Microwave radiometry can estimate distant temperatures by detecting microwave electromagnetic radiation. The sensitivity of the microwave radiometer is also distance-dependent. The microwave radiometer thus serves as a promising instrument for monitoring temperatures at depth away from the catheter-electrode tip in ablative therapy for cardiac arrhythmias.

Calibration↗

Non-invasive temperature profile estimation in a lossy medium based on multi-band radiometric signals sensed by a microwave dual-purpose body-contacting antenna.

Microwave radiometry has during the past two decades been investigated as a non-invasive scheme for measurement of subcutaneous tissue temperatures, basically for monitoring and control in hyperthermic treatment of cancer. In this effort, we test a contact-type, dual-purpose antenna with integral water bolus. To overcome conflicting optimization criteria in the integration of this thermometry technique with heat applicators exhibiting a large effective field size during superficial hyperthermia, a stacked configuration design is proposed, where the radiometer receive antenna (Archimedean spiral) is located on the front (skin) surface of the water bolus and the heating antenna (Dual-Concentric Conductor aperture) is placed on the bolus back surface. The motivation is to achieve homogeneous tissue heating simultaneously with non-invasive thermography of the target tissue under the applicator. This paper addresses the feasibility of predicting one-dimensional depth temperature profiles from multi-band brightness temperatures. The performance is investigated statistically by a Monte Carlo technique on both simulated and real heated-phantom data using up to six radiometric bands. Analysis of measured data shows that during the transient heating period in a solid lossy phantom, the inversion technique exhibits a precision (2sigmaT) and skewness (bias) of estimated compared to actual temperature profiles of better than +/-0.38 degrees C and +/-0.55 degrees C, respectively.

Algorithms↗