Lower Limit Of Sensitivity Research Articles

General regularities of explosion initiation in determining impact and friction sensitivity of an explosive

The impact and friction sensitivities of explosives were measured by 12 methods used in Russia and abroad. Correlations between explosion frequency on devices No. 1 and No. 2 with a “lower sensitivity limit” according to Russian standard 4545–88 and “critical clamping pressure” for the I-6-2 device are obtained. Almost all results are well correlated with critical stress p1 thus representing a good base for explanation of experimental results for impact and friction. The values we obtained determining friction sensitivity are often proportional to p1. The regularities obtained are explained.

Differential diagnosis of hyperthyroidism with highly sensitive assay of blood TTH: clinical review and practical recommendations for use in Russia and USA

Highly sensitive methods for determining the level of TSH, carried out using test kits of the second and third generation, make it possible to differentiate with high accuracy the normal and subnormal levels of TSH in the blood and are currently widely used to examine patients with thyroid pathology. These methods have been used for a long time in clinical practice in the United States of America, and recently they are also increasingly used in Russia. The level of TSH below normal values ​​is determined in almost all cases of hyperthyroidism (with the exception of cases of TSH-secreting pituitary adenoma or resistance of the pituitary to thyroid hormones), which makes it possible to do without additional testing with tyroliberin (TRH). Methods for determining second generation TSH usually have a lower sensitivity limit of about 0.1 mU/L. When using the third generation methods, it is possible to accurately determine the level of TSH up to 0.01 mU/L. The fourth generation methods, which are still under development, will have a lower limit of determination of 0.001 mU/L, but they are unlikely to be used for routine clinical studies in the near future. At the Endocrinology Research Center of the Russian Academy of Medical Sciences in Moscow, third-generation methods are currently being used for routine clinical research (the Amerlight system, produced in Russia by the Amerkard joint venture). In addition to this system, other test systems of both domestic and foreign production are also available in Russia. In the USA, methods for determining TTG of the second and third generation are used. Third-generation systems are noticeably more expensive than second-generation systems. Given that in most patients with hyperthyroidism, the TSH level is in the range of less than 0.1 mU/L, methods for determining the third generation are more preferable. In general, the normal level of TSH in the blood of individuals in a state of euthyroidism is from 0.5 to 5.0 mU/L, although there are some interlaboratory differences in the standards for the level of TSH.

A luminescene method for the quantitative determination of phagocytosis of erythrocytes, of malaria‐parasitized eryithrocytes and of malarial pigment

A method is described for the quantitative measurement of phagocytosis of human erythrocytes, malaria-parasitized erythrocytes and isolated malarial pigment by adherent human monocytes. The method utilizes measurement of haem-elicited luminescence both for the assay of ingested haemoglobin or malarial pigment haem and for the quantification of adherent monocytes. The latter is based on assay of luminescence elicited by cytochrome haem. The method utilizes the same low-cost reagents and equipment for assay of ingested haem and for quantification of adherent monocytes. The method is fast and extremely sensitive. The lower sensitivity limit is 500 monocytes and 10 RBC, or RBC equivalents in the case of malarial pigment, per assay. A detailed protocol with full calculations of a typical phagocytosis experiment of oxidatively damaged RBC, malarial pigment and control RBS is presented.

An Infrared Hygrometer for Atmospheric Research and Routine Monitoring

Abstract The development and testing of a field durable, infrared differential absorption hygrometer is described. This noncontact hygrometer offers reliable operation in harsh environments while maintaining subsecond response speed. A modified exponential response function was derived from laboratory calibration data. Absolute humidity resolution is better than 1% for absolute humidities greater than 2.0 g m−3, and better than 6% for absolute humidities in the range of 0.1–2.0 g m−3. The lower limit of sensitivity is less than or equal to 10 ppmv. A field trial was conducted at White Sands Missile Range, New Mexico, utilizing a total of six humidity sensors and four temperature sensors. The infrared hygrometer was determined to be the most accurate humidity sensor in the field trial, with a dew/frost-point measurement error of less than 0.5°C over the dew/frost-point range of −15° to 10°C. A combination of numerical modeling, laboratory measurements, and field data was used to investigate possible humidi...

Pharmacokinetics and Blister Fluid Penetration of Brodimoprim in Adults

We investigated the pharmacokinetic properties of brodimoprim (B), a new diaminopyrimidine, including its penetration into suction blister fluid (SBF) after a single or multiple oral dose in 15 patients with a mean age of 61.5 +/- 9.3 yrs, suffering from respiratory tract infections with normal renal and hepatic function. Patients were divided into 3 groups of 5 cases each, according to treatment plan: Group I = B 400 mg single dose day 1; Group II = B 400 mg qD day 1 and 200 mg qD days 2 to 4; Group III = B 200 mg BID day 1 and 200 mg qD days 2 to 4. Concentrations were determined microbiologically using B. subtilis ATCC 6633 as the test organism with a lower limit of sensitivity of 0.37 mg/l. With a single oral dose of 400 mg (Group I) a computed serum Cmax of 2.9 +/- 0.6 mg/l was observed 5.6h after administration, with a elimination half-life (t1/2 beta) of 32.3 +/- 4.1 h. In SBF a mean peak of 1.9 +/- 0.6 mg/l was reached after 6h with a t1/2 beta of 34.7 +/- 5.4 h and a penetration index (Pl), obtained by the AUCSBF/AUCs percent ratio of 61%. With multiple doses serum peak concentrations increased significantly, while the time to reach the peak (Tmax) was shorter (3.7-4.2 h) than after a single dose. Main kinetic parameters, such as t1/2 beta, mean residence time (MRT), elimination rate constant (Kel) and AUC, were significantly higher in Group II and III patients than in Group I cases. Similar differences were observed among the main SBF kinetic parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved assay for the quantification of 11-dehydrothromboxane B 2 by gas chromatography—mass spectrometry

Endogenous thromboxane production is best assessed by the measurement of its excreted metabolites, of which 11-dehydrothromboxane B 2 (11-dehydro-TxB 2) is most abundant. Gas chromatographic—mass spectrometric assays have been developed for this compound but suffer from the presence of co-eluting impurities which make the measurement of 11-dehydro-TxB 2 difficult. Furthermore, these assays are often time-consuming. We now report a modified assay for the measurement of this compound employing gas chromatography—mass spectrometry which alleviates the problem of co-eluting impurities primarily through modification of extraction and chromatographic methods. Furthermore, the time to complete the assay is significantly shortened. It is adaptable to both urine and plasma. Precision of the assay is ± 7% and accuracy is 90%. The lower limit of sensitivity in urine is approximately 20 pg/mg creatinine. Normal levels of urinary excretion of this metabolite were found to be 370 ± 137 pg/mg creatinine (mean ± 1 S.D.) and normal plasma levels were found to be 1.5 ± 0.4 pg/ml (mean ± 1 S.D.). Urinary excretion of 11-dehydro-TxB 2 is markedly altered in situations associated with abnormalities in thromboxane generation when quantified using this assay. Thus, this assay provides a sensitive and accurate method to assess endogenous thromboxane production and to further explore the role of this compound in human disease.

ＧＣ／ＭＳによる血しょう中Ｅｐｅｒｉｓｏｎｅの高感度定量

A gas chromatography-mass spectrometric method was employed for the determination of the antispasmodic drug, eperisone, in plasma. Excellent sensitivity was achieved by the selection of the base ion peak at m/z 98 of eperisone and a suitable internal standard, tolperisone, and by using a cyanopropylphenyl-bonded fused-silica capillary column. The lower limit of sensitivity was 10 pg/ml with a signal-to-noise ratio of 3. Another internal standard, decadeuterium labelled eperisone, was inferior to tolperisone in terms of accuracy and reproducibility at low levels of eperisone. The present method allows the determination of eperisone in human plasma after an oral administration of eperisone hydrochloride.

Variability in Declining Haloperidol and Reduced Haloperidol Plasma Concentrations upon Haloperidol Cessation

Plasma concentrations of haloperidol and its reduced metabolite were measured in 6 schizophrenic patients after discontinuation of oral haloperidol treatment. Patients were on haloperidol 10mg twice daily for at least 2 to 4 weeks prior to cessation of treatment to ensure haloperidol steady-state concentrations had been achieved. Blood samples were obtained at 12, 24, 36, 60 and 84 hours following drug discontinuation. Haloperidol and reduced haloperidol were assayed by high-performance liquid chromatography with a lower limit of sensitivity of 0.2 μg/L and inter- and intra-assay coefficients of variation of less than 4 to 12% at 2 to 10 μg/L. Declining plasma concentrations of both haloperidol and reduced haloperidol were observed in each patient. Three of 5 patients had increased oscillations of either plasma haloperidol or reduced haloperidol concentrations at different times during the 84-hour period following withdrawal of haloperidol therapy. It is suggested that enterohepatic recycling could account for these oscillations.

The effect of age and diabetes mellitus on serum levels of lymphotoxin

To determine whether chronic hyperglycemia or aging is associated with increased serum levels of lymphotoxin, sera were obtained from 29 insulin-treated diabetic patients and 50 healthy subjects ranging in age from 22 to 97 years old. An ELISA system specific for human lymphotoxin was developed with the lower limit of sensitivity at 76 pg/ml and interassay coefficient of variation of <7%. Serum levels of tumor necrosis factor (TNF) alpha, interleukin 1 (IL-1) alpha and beta were measured with previously described ELISA system. The WEHI 164 cytotoxicity assay was used to measure bioassayable TNF-like activity. Of the 29 diabetic patients, seven had detectable serum immunoreactive lymphotoxin levels and three had bioassayable serum levels of TNF-like activity. In contrast, only one healthy subject had detectable serum lymphotoxin levels (p<0.01). Of the 22 diabetic patients who did not have detectable levels of lymphotoxin, 5 had detectable TNFα, 4 had detectable IL-1α, and none had detectable IL-1β levels. Thus, there was no correlation between serum lymphotoxin level and serum levels of TNF α, IL-1 α, or IL-1 β. Aging is not associated with altered serum levels of lymphotoxin while 24% of diabetic patients have increased serum levels of immunoreactive lymphotoxin.

HPLC analysis of free amino acids and amino acids of total proteins in cultured cells: An application to the study of rat sertoli cell protein metabolism

A simple, rapid and, sensitive HPLC method, coupled with fluorometric detection, has been worked out and employed to determine the intracellular free amino acid concentrations and the amino acid composition of total proteins in rat Sertoli cell primary culture. Sertoli cells were isolated enzymatically from testes of 20- and 28-day-old rats and cultured at 32°C in Eagle's minimum essential medium. On the second day of culture, cell monolayers were quickly rinsed with ice-cold saline, immediately frozen in liquid nitrogen, accurately harvested, and homogenized in 10% trichloroacetic acid. Tissue free amino acids were determined in the acidic soluble fraction following neutralization, while the precipitate was hydrolyzed for the evaluation of the fractional content of amino acids into total proteins. Amino acid samples were derivatized with o-phthaldialdehyde/3-mercaptopropionic acid and resolved by a linear one-step acetonitrile gradient in 12.5 m m sodium phosphate buffer, pH 7.2, employing a 5-μm particle size reversed-phase column. Fluorescence was monitored with excitation at 330 nm and emission at 450 nm. Under these conditions all major physiological amino acids could be satisfactory separated, identified, and subsequently quantified with the aid of standards. The run time was about 50 min; the linearity was excellent over a large range of concentrations (1–800 pmol) and the lower limit of sensitivity appeared to be 0.5 pmol. This method permits us to demonstrate age-dependent modifications in the intracellular amino acid pool and to adequately evaluate the process of protein synthesis in cultured Sertoli cells. The precise evaluation of the specific activity in the amino acid precursor pool allows us the quantitative estimation of protein synthesis by incorporation of a radioactive amino acid; the fractional content of the amino acid precursor into total cell protein was used for the calculation of the rate of protein synthesis.

Reduction in plasma human immunodeficiency virus ribonucleic acid after dideoxynucleoside therapy as determined by the polymerase chain reaction.

Cell-free HIV RNA in plasma was detected and quantitated after antiviral therapy by the polymerase chain reaction. RNA was extracted from plasma, reverse transcribed to cDNA, amplified by polymerase chain reaction, and quantitated by absorbance based on an enzyme-linked affinity assay. 72 HIV antibody-positive subjects had one plasma sample taken. 39 who were not receiving antiretroviral therapy at the time had a mean plasma HIV RNA copy number of 690 +/- 360 (mean +/- SEM) per 200 microliters of plasma, while 33 subjects who had been receiving zidovudine therapy for a minimum of 3 mo had a mean copy number of 134 +/- 219 (P less than 0.05). 27 additional HIV antibody-positive patients had two plasma samples taken before and 1 mo after initiating dideoxynucleoside therapy. Plasma HIV RNA copy number fell from 540 +/- 175 to 77 +/- 35 (P less than 0.05). Finally, nine of these subjects had two baseline samples obtained before initiating therapy and two posttreatment samples 1 and 2 mo after therapy was begun. Mean plasma RNA copy number declined from 794 +/- 274 to less than 40 (below the lower limit of sensitivity) after 1 mo of therapy, with suppression maintained after 2 mo of therapy. These results suggest that gene amplification can be used to detect and quantitate changes in plasma HIV RNA after dideoxynucleoside therapy. Plasma HIV polymerase chain reaction may be a more sensitive marker to monitor antiviral therapy, particularly in asymptomatic patients where measurement of p24 antigen or quantitative plasma cultures are negative.

A Simple and Sensitive HPLC Assay for Piroxicam in Plasma and Its Application to Bioavailability Study

Abstract A rapid, simple and selective method for the determination of piroxicam in human plasma is described. The sample was prepared by direct plasma protein precipitation. Isoxicam was used as the internal standard. For sample analysis, 100 μl of the internal standard (isoxicam 500 μg/ml) and 50 μl of 60% w/v trichloroacetic acid were added to the 500 μl of plasma. After brief vortex and centrifugation, the clear supernatant (70 μl) was injected onto the HPLC column. Chromatographic separation and quantitation was performed by reversed-phase HPLC using a 5 μm CN (Spherisorb) microbore column. The mobile phase consisted of an acetronitrile-water mixture (6: 94, v/v) containing 10 mM Na2HPO4, adjusted to pH 2. The eluant was monitored at 363 nm. The lower limit of sensitivity for piroxicam is 0.05 μg/ml (i.e., 50 ng/ml). The standard curve was linear over the concentration range of 0.05 to 10 μg/ml. The intra- and inter-assay coefficients of variation were less than 8%. Applicability of the method is dem...

Liquid Chromatographic Determination of Cyclosporine-A in Blood, with Chromosorb P Columns Used for Sample Purification

Abstract A fast liquid-chromatographic determination of whole-blood cyclosporine A concenration is described. A sample preparation consisting of diethyl ether extraction and Chromosorb P column purification of extract, requires 1 mL of whole blood and takes 10 min of technical effort per sample. A reversed-phase C1 column (5-μm particles) is used, with acetonitrile/methanol/water (20/45/35 by vol) as mobile phase. Cyclosporine A is quantified by absorbance at 214 nm, with cyclosporine D as internal standard. Chromatographic development is complete in 8 min. Linearity is verified by a five-point calibration curve in the range 50–900 μg/L, correlation coefficient r>0.998, y = 0.001x − 0.053. Lower limit of sensitivity is 25 μg/L. Extraction efficiency was over 70%, accuracy varied between −7.1% and +3.3%s, CVs were <5.8% within run, <7.5% between runs. No interference was observed from both endogenous compounds, and 33 drugs eventually co-administered during immunosuppression. Over 1,000 patient samples have been analysed by this method in our laboratory in about one year, without any sign of column deterioration.

High Performance Liquid Chromatographic Analysis of Desipramine in Human Plasma Using a Microbore Column Technique

Abstract A reversed-phase, isocratic HPLC method has been developed for the quantitation of desipramine in human plasma. the method involved the use of cloimpramine as an internal standard. the chromatographic separation was accomplished with a mobile phase comprising acetonitrile-aqueous solution (60:40. v/v) containing 10 mM disodium hydrogenphosphate and 80 mM sodium dodecyl sulfate adjusted to pH 2. the mobile phase was pumped at a flow rate of 0.5 ml/min. the column used was a microbore column (2 mm I.D. × 100 mm) packed with a C18 reversed-phase material (5μm ODS Hypersil). Plasma samples were extracted at basic pH with diethyl ether followed by back-extraction into 0.1 N sulfuric acid. Using UV detection at 250 nm, the lower limit of sensitivity was 10 ng/ml. the inter- and intra-assay coefficients of variation were found to be less than 10%. the assay procedure was applied to a long term oral dosing study in patients to monitor the plasma concentration of desipramine.

Quantification of the major urinary metabolite of prostaglandin D 2 by a stable isotope dilution mass spectrometric assay

Prostaglandin D 2 (PGD 2) has been found to be an important pathophysiological mediator in a number of human disorders. Thus a means to assess the endogenous production of PGD 2 is of considerable clinical value. To accomplish this goal, we developed a method for the quantification of the major urinary metabolite of PGD 2, 9α, 11β-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid, by gas chromatography/negative ion chemical ionization mass spectrometry. This metabolite was chemically synthesized and converted to an 18O 4-labeled derivative for use as an internal standard. Novel derivatization and purification procedures were incorporated in the assay taking advantage of the ability of the lower side chain of this molecule to undergo cyclization at acidic pH to form a hemiketal, γ-lactone, and uncyclization with methoximation. Precision of the assay is ±7% and accuracy is 96%. The lower limit of sensitivity is approximately 50 pg. Normal levels for the urinary excretion of this metabolite in 18 normal adults was found to be 1.08 ± 0.72 ng/mg creatinine (mean ± 2SD). Substantial elevations in the urinary excretion of the metabolite were found in clinical situations in which prostaglandin D 2 has been shown to be released in increased quantities. Thus, this assay provides a sensitive and accurate method to assess endogenous production of prostaglandin D 2 as a means to explore the pathophysiological role of prostaglandin D 2 in human disease.

High-performance liquid chromatographic separation of the three stereoisomers of diaminopimelic acid in hydrolysed bacterial cells

A high-performance liquid chromatographic method able to separate the three stereoisomers of diaminopimelic acid (DAP) was developed. It consists of the reaction of DAP with 1-fluoro-2,4-dinitrophenylalanine amide (FDAA), followed by chromatographic analysis of the diastereomers under reversed-phase conditions. With this method whole cell hydrolysates of different bacterial strains were analysed. The DAP derivatives can be resolved from one another and from complex mixtures of other amino acids. The precision of the derivatization and the day-to-day reproducibility were calculated and were in the range 0.5–2%. The lower limit of sensitivity is ca. 600 ng for a mixture of the three isomers, which is sufficient for the detection of DAP even starting from small amounts of biological material. The method was applied to the analysis of the whole cell hydrolysate of Kineosporia aurantiaca, an unusual strain in which L, L- and “meso”-isomers are both present.

Measurement of von Willebrand Factor Antigen in Plasma and Platelets with an Enzyme-Linked Immunosorbent Assay Based on Two Murine Monoclonal Antibodies

Two murine monoclonal antibodies, raised against von Willebrand factor (vWF), were used to construct an enzyme-linked immunosorbent assay (ELISA), for quantitation of vWF antigen (vWFAg) in human plasma and platelets. This assay had a lower limit of sensitivity of 0.0001 IU/ml in buffer, and thus is one to two orders of magnitude more sensitive than other ELISA assays which have been reported. The intraassay, interassay and interdilution coefficients of variation were 4.1, 10.4 and 9.9%, respectively. In normal plasma (n = 20), the vWFAg level was 0.83 (range: 0.42-1.25) IU/ml. In normal washed platelets (n = 10), 0.35 (0.25-0.49) IU/10(9) platelets was found. In plasma obtained from various patient groups the following vWFAg levels (geometric mean and range) were observed: von Willebrand's disease (n = 19): 0.18 (0.02-0.77) IU/ml; patients with liver cirrhosis (n = 20): 3.73 (1.68-9.20) IU/ml; patients with pregnancy-induced hypertension (n = 20): 4.14 (2.28-7.44) IU/ml and patients with malignant disease (n = 10), 2.54 (1.51-5.60) IU/ml. A linear correlation was found between vWFAg levels measured with a polyclonal antibody based Laurell electroimmunoassay (r = 0.92, n = 58) or with a polyclonal antibody based ELISA (r = 0.94, n = 64). The present assay is based on stable and reproducible reagents and allows the specific measurement of vWFAg in plasma and in platelets. This assay may constitute a useful tool for the further investigation of clinical conditions associated with changes in vWFAg levels. In addition, its high sensitivity may facilitate a more detailed study of platelet vWFAg in normal and in pathological conditions.

Limits of sensitivity of inertial seismometers with velocity transducers and electronic amplifiers

Abstract Portable instruments such as ocean bottom seismographs and the PASSCAL recorders often use rugged, portable geophones. The desire to use such sensors for relatively low-frequency work has raised questions about the limits of their sensitivity. The lower and upper frequency limits of performance of seismic sensors are determined by the sensor's mass, period, and Q, and by the amplifiers used with those sensors. We have tested Mark Products 1 Hz, 2 Hz, and 4.5 Hz velocity transducers against Streckeisen seismometers in order to examine the limits of their performance in measuring ground noise, particularly at low frequencies. Among the velocity transducers, only the 1 Hz Mark Products L-4 sensor provided good resolution of the 6-sec microseism peak. For this sensor, the lower limits of sensitivity was at approximately 0.06 Hz, although this depends on the amplifier used and the noise level at a given site. The amplifiers examined included conventional, low power, and commutating auto-zero operational amplifiers. It was found that the noise levels of the amplifiers intersected the ground noise level at frequencies ranging between 0.06 and 0.2 sec, depending on the amplifier and the exact circuit design. Measurements indicated that by modeling the amplifier noise for a given circuit correctly, the performance of an amplifier can be predicted with a high degree of accuracy, obviating the need for actual circuit construction to determine performance in the field. Given the very steep slope of the ground noise spectrum between 0.05 and 0.1 Hz and the rapid fall off in a seismometer's output below its resonant frequency, it would require a lowering of amplifier noise by more than an order of magnitude to be able to resolve ground noise at frequencies lower than 0.05 Hz using relatively small geophones such as the L-4. To resolve ground noise at lower frequencies, it is necessary to use a seismometer with a displacement transducer to sense the mass position, such as Guralp or Streckeisen sensors.

Separation and quantitation of the polyamine biosynthesis inhibitor d,l-α-difluoromethylarginine and other guanidine-containing compounds by high-performance liquid chromatography

The arginine decarboxylase inhibitor difluoromethylarginine (DFMA) is an important tool in the study of polyamine metabolism, particularly with respect to the human pathogen Trypanosoma cruzi. This paper demonstrates a unique method for the detection and quantitation of intracellular DFMA using the fluorogenic agent 9,10-phenanthrenequinone. After separation of cell extracts by HPLC, DFMA can be accurately and reproducibly quantified with a lower sensitivity limit of 0.1 nmol by this simple fluorometric method. This assay can also be used to detect other guanidine-containing compounds such as arginine, agmatine, creatinine, and hirudonine, but not substituted guanidines such as aminoguanidine and creatine, or the structurally related amidines such as benzamidine and pentamidine.

Rapid Spectrophotometric Determination of Plasma Carnitine Concentrations

A spectrophotometric enzymatic assay for plasma carnitine concentrations has been automated on the Monarch 2000. Prior to the assay, each plasma sample was divided into three fractions, ie, free carnitine, acid-soluble carnitine and total carnitine, in order to determine the concentration of both free and esterified carnitine. Using the method developed by Tachikawa et al (Seikagaku 56:998, 1984), each of the samples was then chromatographed on an anion exchange resin to eliminate those compounds which could adversely impact the accuracy of the enzymatic assay for carnitine. After the completion of these preparatory steps, 32 specimens were assayed in less than 16 min on the Monarch 2000 with a high degree of both accuracy and precision. The assay was linear over a wide concentration range (5.0-80 mumol/liter), with the lower limit of sensitivity being 5.0 mumol/liter. The coefficient of variation (CV%) of the within run precision was 2.1%, 2.8%, and 6.7% for the determinations of free carnitine, acid-soluble carnitine, and total carnitine, and 17.4% and 27.8% for the calculated values of short-chain and long-chain acylcarnitines, respectively. The CV% of the between run precision for the same fractions was 6.5%, 2.7%, 3.8%, 14.2%, and 14.3%, respectively. When authentic L-carnitine was added to the plasma, the mean recovery rate was 94.7 +/- 11.0%. Reference values were determined using plasma obtained from 40 healthy adult volunteers.