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Pharmacokinetic interaction with digoxin and glucocorticoids in rats detected by radio-immunoassay using a novel specific antiserum.

We previously prepared a more specific antiserum (Antiserum-I) to digoxin (Dx) compared with commercially available anti-Dx antiserum (Antiserum-II), clinically used in the therapeutic drug monitoring of Dx. The aims of this study are to compare Dx disposition kinetics by radio-immunoassay (RIA) using Antiserum-I and Antiserum-II, and evaluate the drug-drug interaction with Dx and glucocorticoids in rats. When Dx metabolites were added to rat serum containing Dx, the recovery ratios using Antiserum-I showed 100 to 110% and were remarkably lower than those using Antiserum-II. In rats, serum concentration-time courses of Dx after a single i.v. or p.o. administration of Dx (0.017 mg/kg) by RIA using Antiserum-I were much lower than those using Antiserum-II. The area under the concentration-time course of Dx was significantly lower than that using Antiserum-II and the total body clearance values were significantly higher, while an obvious change of bioavailability was not observed. When using Antiserum-I, rats twice and six times pretreated with dexamethasone (75 mg/kg/day, i.p.) and prednisolone (69 mg/kg/day, i.p.), respectively, showed significant change of the pharmacokinetic parameters of Dx compared with the control rats. In contrast, using Antiserum-II, it took three and nine times of pretreatment with dexamethasone and prednisolone, respectively, to significantly change the parameters of Dx. In conclusion, these results demonstrate that Antiserum-I is very useful not only to more precisely monitor serum Dx levels, but also to determine earlier the drug-drug interaction with glucocorticoids than Antiserum-II.

Animals↗

[Volar distal radio ulnar joint dislocation, case report and literature review].

The authors report the case of a volar distal radio ulnar joint dislocation. The rarity of this lesion seems to be linked to the anatomical relationship of the distal portion of the ulna with the tendons of the extensor carpi ulnaris and the tendon of the extensor digiti minimi. Early diagnosis based on physical examination and radiology gives a better prognosis for closed treatment, reserving surgery for failure or irreducible luxations.

Aged↗

Curcumin: a new radio-sensitizer of squamous cell carcinoma cells.

PURPOSE: Curcumin, a potential chemopreventive agent, was found to inhibit cancer cells in S/G2M phases of the cell cycle, when radiation is more effective. The purpose of the current study was to investigate whether curcumin can sensitize squamous cell carcinoma (SCC) cells to the ionizing effects of irradiation. METHODS: Curcumin (3.5 microM) was added for 48 hours to an SCC cell line prior to irradiation. Cell growth (counts) and colony-formation (colonogenic assay) were examined after radiation. RESULTS: Incubation with curcumin only (3.75 microM) for 48 hours did not decrease the number of cells or the ability to form colonies in the absence of radiation. However, in plates that were exposed to 1-5 Gy of radiation, cell counts dropped significantly if pretreated with curcumin with a maximal effect at 2.5 Gy (where the cell counts dropped from 1240 to 1017, P < 0.001). The colonogenic assay revealed a significant decrease in the ability to form colonies following pretreatment with curcumin in all radiation doses ( P < 0.05). CONCLUSIONS: Given the appropriate doses, curcumin exhibits radio-sensitizing effects on SCC cells in vitro.

Carcinoma, Squamous Cell↗

Radio-detoxified endotoxin activates natural immunity: a review.

It is well demonstrated that serial endotoxin injections produce endotoxin tolerance and elevate the natural immunity/resistance. However, such injections may also have harmful effects such as high fever, hypotension and abortion. For this reason endotoxin (LPS) injections are not suitable to enhance nonspecific resistance in endotoxin-sensitive species like man. Various techniques have been designed (physical, chemical, etc.) for the detoxification of endotoxins while the beneficial effects are maintained. Perhaps one of the best detoxification techniques is the treatment with ionizing radiation. The irradiation of LPS with 60Co (150 kGy) decreased its toxicity in a dose-dependent manner. Such radio-detoxified endotoxin (RD-LPS) preparations show decreased toxicity whereas the beneficial effects were preserved. Irradiation causes marked chemical alterations in LPS, such as a decrease of glucosamine, ketodeoxyoctonic and fatty acids. A single parenteral RD-LPS injection prevents various forms of shock in experimental animals. This preparation has a membrane-stabilizing effect, and thereby it can prevent the membrane-damaging effect of LPS and of some cytostatic agents. Unlike endotoxin, RD-LPS has little hypotensive effects, and the pretreatment with this preparation can prevent practically all the hemodynamic changes induced by LPS. LPS plays an important role in the pathogenesis of intestinal syndrome of radiation disease, which may be prevented by RD-LPS pretreatment up to 70% in rats. RD-LPS retains the adjuvant activity of LPS, and it serves as a good adjuvant for inactivated virus vaccines. RD-LPS can also evoke the regeneration of the immune system in irradiated animals. The decrease of nonspecific resistance in immunodeficient or immunosuppressed patients is the most important cause of opportunistic infections that may lead to sepsis like in endotoxaemia and pneumonia. Organ transplant recipients commonly die of septicaemia. Antilymphocyte serum (ALS) is used in such patients as an immunosuppressant. The augmentation of natural resistance and the induction of endotoxin tolerance are of major significance in such patients. In ALS-treated rats RD-LPS induces also tolerance against the lethal dose of LPS. This demonstrates that in spite of the suppressive effect of ALS on T-lymphocytes the induction of LPS tolerance (the enhancement of natural resistance) remains normal. Facultative pathogenic organisms may flourish and cause disease when specific and nonspecific resistance is impaired. RD-LPS can produce a significant proliferation of lymphoid cells in germ-free animals which are immunodeficient. Many other beneficial effects are preserved by RD-LPS preparations, such as the activation of macrophages and of the reticuloendothelial system and antitumor activity. On the basis of these favorable experimental results, RD-LPS has been tested on 350 surgical patients suffering from gastrointestinal tumors, patients suffering from acquired immunodeficiency syndrome (AIDS) and cancer patients treated with CYSPLATIN. RD-LPS treatment prevented sepsis and activated the bone marrow function in these patients.

Journal Article↗

Optical emission spectroscopy of benzyl radicals produced in a radio-frequency plasma.

The benzyl radical was studied by optical emission spectroscopy in gas phase. This radical was produced in a radio-frequency (RF, 13.56 MHz) discharge, using benzyl alcohol (ØCH(2)OH) as a precursor. The fluorescence from the first excited electronic state 1(2)A(2) to ground state 1(2)B(2) (450 nm) was studied as a function of several external parameters (pressure, RF power, electrodes and mixtures of the inert gases Ar, Ne, He, N(2), with the precursor). We also used a DC discharge to produce this radical but, in this case, the decomposition was fast. We observed changes in the electronic transitions of this radical, and found the best conditions to study it by optogalvanic spectroscopy.

Argon↗

[Radio-guided resection of residual metastatic lymph node from a previously resected neuroendocrine tumor].

Neuroendocrine tumors are slowly growing and carry a high risk of recurrence. Somatostatin receptor scintigraphy is considered as the gold standard for preoperative evaluation and postoperative follow-up. The use of an intraoperative detection probe makes easier a complete resection of abdominal residual or recurrent tumor. These resections may be incomplete because of the small size of the tumor and the postoperative adhesions. Radio-guided surgery is recommended in order to reduce the need for reoperation.

Humans↗

[Radio-guided occult lesion localization combined with sentinel node biopsy in women with breast cancer].

INTRODUCTION: The practice of intratumoral radiocolloid injection for sentinel node biopsy (SNB) allows localization of nonpalpable breast tumors in the same surgical intervention, using the technique known as radio-guided occult lesion localization (ROLL). PATIENTS AND METHOD: We present our experience with the combined use of both techniques (SNB and ROLL). A total of 233 patients were retrospectively analyzed: 65 patients underwent ROLL and 168 patients underwent wire-guided localization (control group) as the excision modality. Both groups had comparable pathologic and radiologic features. RESULTS: Complete excision of the lesion was achieved at the first attempt in only 169 patients. There were no significant differences among groups in surgical margin status (margins were adequate in 80% of ROLL patients vs 69.9% of non-ROLL patients) or in maximum specimen diameter (6.85 cm vs 6.52 cm, respectively). CONCLUSION: We conclude that ROLL is an acceptable alternative to wire-guided localization in patients with nonpalpable breast tumors undergoing SNB, leading to easier lesion excision and greater patient comfort.

Breast Neoplasms↗

Radio-enzymatic determination of histamine: interference by fluoride and possible activation of histamine methyl transferase.

The reproducibility of a radio-enzymatic method for determining plasma histamine was found to be affected by the anti-coagulant used for collecting blood. Recovery experiments from whole blood indicated that heparin yielded values that were more accurate than with EDTA or sodium fluoride; fluoride gave a mean value which was +41% higher than with heparin (P=0.054). Addition of fluoride to a standard calibration curve, and of increasing amounts to aliquots of 5 ng histamine also yielded higher values than in controls, up to +15% (P<0.1) and +14.1% (P=0.03) respectively. Fluoride did not affect the detecting system and was not contaminated with histamine; nor did it breakdown the methyl donor, S-adenosyl-L-methionine. It is concluded that heparin is the anti-coagulant of choice and that fluoride may activate histamine methyl transferase from pig brain. Fluoride may possibly have a biological role as an enzyme-activator and a usefulness in the therapy of mastocytosis.

Edetic Acid↗

Critical evaluation of the logit-log plot for the radio assay of vitamin B12.

The dose-response calculation for radio assay of vitamin B12 is carried out using a straight line and a third degree curve to fit the experimentally obtained calibration points. It is shown that high dispersion of the calibration points with respect to the regression line can lead to errors in the calculation of the response. The calculation of the mean dispersion sx with respect to the regression line turns out to be a good criterion for checking the accuracy of the results.

Evaluation Studies as Topic↗

LQG controller design using GUI: application to antennas and radio-telescopes

The Linear Quadratic Gaussian (LQG) algorithm has been used to control the JPL's beam wave-guide, and 70-m antennas. This algorithm significantly improves tracking precision in a wind disturbed environment. Based on this algorithm and the implementation experience a Matlab based Graphical User Interface (GUI) was developed to design the LQG controllers applicable to antennas and radiotelescopes. The GUI is described in this paper. It consists of two parts the basic LQG design and the fine-tuning of the basic design using a constrained optimization algorithm. The presented GUI was developed to simplify the design process, to make the design process user-friendly, and to enable design of an LQG controller for one with a limited control engineering background. The user is asked to manipulate the GUI sliders and radio buttons to watch the antenna performance. Simple rules are given at the GUI display.

Journal Article↗

A dynamic simulator to evaluate distal radio-ulnar joint kinematics.

In order to perform cadaveric biomechanical studies of the human forearm and distal radio-ulnar joint, a dynamic simulator has been constructed. The device is based upon a Plexiglas frame, to which the ulna is secured in a vertical orientation and the humerus in a horizontal orientation. The hand is secured in a sliding bar linkage to a stepper-motor that is used to rotate the forearm. The tendons to be loaded are connected to pneumatic actuators that provide agonist and antagonist muscle loading resulting in torque along the forearm axis. The muscle loading profiles and magnitudes are programmable as a function of the pronation-supination position and direction. A magnetic tracking system is used to collect three-dimensional kinematics data of up to four segments, in conjunction with the muscle tendon loads, forearm torque and other prescribed experimental measures. All functions are under PC control using custom software written with LabVIEW (National Instruments, Austin, TX). For the DRUJ testing, the validity of the tendon loading protocol to produce physiologic torque/rotation patterns was verified using in vivo data. The relationship of individual muscle forces to forearm torque was determined by a cadaveric study.

Biomechanical Phenomena↗

Method for radio-capillary gas chromatography employing a modified oxidation-reduction train and flow-through detector.

A conventional radioactivity monitor was modified by reducing the volume of the oxidation-reduction train and gas proportional counting tube to permit coupled radio-capillary gas chromatographic analysis of labeled isomeric metabolites. The utility of this radioactivity monitoring technique was demonstrated by separating 3H-labeled sesquiterpene olefins. The advantages and limitations of mass (thermal conductivity) and radioactivity detection by this method are discussed.

Chromatography, Gas↗

Radio gas chromatography for evaluation of sub-cellular hormone synthesis in the androgen insensitivity syndrome.

This paper gives a description of a radio gas-liquid chromatographic method for the evaluation of androgen hormone synthesis patterns in the testicular tissue of a patient suffering from the androgen insensitivity syndrome (AIS). A modified dual-column gas chromatography system, equipped with column switching facilities and a radioactivity monitor run parallel to a flame ionisation detector, enables the monitoring of radioactive intermediates of testosterone anabolism and catabolism, generated from a labelled precursor. Tissue preparations were incubated with tritiated pregnenolone for 45 min at 37 degrees C. Steroid hormones were stripped from the aqueous phase by solvent extraction and analysed by gas chromatography as methoxitrimethylsilyl (MO-TMS) derivatives on a 15 m X 0.32 mm I.D. fused-silica capillary column coated with DB-5. The results reveal abnormal enzyme kinetics due to accelerated precursor utilisation. The findings reflect the pathophysiology of AIS at the sub-cellular level of the androgen hormone target organ.

Adolescent↗

Radio-contrast enhancement of urinary tract stones.

Most urologists treating stone disease with any method (ESWL, PCL, URS) have encountered problems of poor stone visualization with fluoroscopy. This difficulty to localize urinary tract (UT) stones or fragments may result in incomplete stone extraction, prolonged surgery and increased risk of recurrence and post-operative complications. We have sought and found means to increase the radioopacity of mineral UT stones by a simple pre-operative perfusion technique. The capacity of radioopacification has first been demonstrated in in vitro incubations of fragments of human mineral stones with aqueous solutions of barium, of the lanthanides and of the two natural actinides. Most of the incubations led to considerable radio-contrast enhancement and heavy metal incorporation, measured by X-ray fluorescence analysis. Dogs with implanted human stone fragments were used as an in vivo model. The UT were perfused through a retrograde pyelic catheter with heavy metal salts solutions, the ensuing radioopacification of the implanted UT-stones was estimated by abdominal radiographies and the metal incorporation was measured on the retrieved stones. Considerable radioopacity enhancement together with heavy metal incorporation was observed for the following elements: Sr, Ba and the lanthanides Gd and Yb. The pathological evaluation of the urothelial linings from animals treated with lanthanide salt showed no toxic effects.

Animals↗

Radio-immunoassay detection of interferon-gamma in urine after intravesical Evans BCG therapy.

Our previous studies suggested that interferon-gamma (IFN gamma) was produced in the local immune response to intravesical BCG. To confirm this we modified a commercially available radio-immunoassay for detection of this lymphokine in urine. The urinary levels of IFN gamma were compared in serial urine samples taken from six patients undergoing treatment with Evans strain BCG and seven patients receiving intravesical mitomycin C/epirubicin. IFN gamma was detected consistently in response to BCG with levels reaching a peak (mean 67.1 U/ml., range 7.9 to 155.9 U/ml.) four to six hours post-instillation whereas after other intravesical agents no IFN gamma was detectable after seven of 13 instillations. After the remaining six instillations lower levels were detected (mean 7.4 U/ml., range 0.6 to 22.4 U/ml.). The difference in peak levels between the two groups was statistically significant (p less than 0.001 Mann Whitney U test). These results are further evidence of specific cellular immune activity in response to intravesical BCG therapy and suggest anti-tumour mechanisms similar to allograft rejection and autoimmunity.

Administration, Intravesical↗

Radio-sensitive murine thymoma cell line 3SB: characterization of its apoptosis-resistant variants induced by repeated X-irradiation.

3SB, a mouse thymoma cell line, is one of the most radio-sensitive cells (D0 = 0.3 Gy), and its rapid apoptosis (4 h after 5 Gy irradiation, 90% apoptosis) seems to play a decisive role in enhancing the radiosensitivity. To understand the molecular mechanisms underlying extremely high radiosensitivity and rapid apoptosis, we attempted to isolate X-ray-resistant (XR) variants from 3SBH5, a stable subclone of 3SB, by repeating exposure of the cells to 2-5 Gy X-rays. Four independent stable XR variants, R111, R223, R316 and R429, were isolated by the repeated irradiation protocols. All XR cells possessed about 3 times higher D10 values than that of their parental 3SBH5. They were also resistant to apoptosis; only 10% cells underwent apoptosis 4 h after 5 Gy irradiation. The p53 protein was induced in all the cell lines after 5 Gy X-irradiation. These variants showed a cross resistance to a chemical reagent daunorubicin (DNR) that is known to be involved in the ceramide-mediated apoptosis. DNR, as well as C2-ceramide (5 muM) induced apoptosis in parental 3SBH5 cell, but not in two XR variants, R233 and R316 cells. Present result suggests that the induction of X-ray resistance by repeated X-irradiation might be achieved, at least partly, by the enhanced resistance to the ceramide-mediated apoptosis.

Animals↗

24-hour recordings of blood pressure, heart rate and behavioural activity in rabbits by radio-telemetry: effects of feeding and hypertension.

We used radio-telemetry to measure 24-hour rhythms of systolic, diastolic and mean blood pressure, heart rate and behavioural activity in conscious rabbits, which were maintained under normal day/night rhythms and restricted feeding. Over three consecutive days, all variables showed little change between day-period and night-period, except for a pronounced rise in the afternoon, coinciding with the presentation of pellet food. Mean blood pressure increased during this period from baseline values between 78-82 mm Hg to a peak of 89-91 mm Hg. At the same time heart rate rose from baseline values of 147-161 b/min to a peak of 206-234 b/min and behavioural activity scores rose from 11-31 counts/h to a peak of 52-81 counts/h. Changing the time at which pellet food was presented to the rabbits from the early afternoon to the early morning, caused a complete and immediate shift of the peak of blood pressure and heart rate to the morning period. Chronic intravenous infusion of angiotensin II caused a significant increase in blood pressure (24-hour average: 80 +/- 1 vs. 114 +/- 7 mm Hg) but did not alter basal heart rate or behavioural activity. The increase in heart rate and blood pressure seen with food presentation was attenuated with angiotensin II infusion. These data show that in rabbits diurnal changes in blood pressure, heart rate and activity were determined to a large extent by timed feeding. In addition, in rabbits with angiotensin-induced hypertension the food-induced changes in blood pressure and heart rate were blunted.

Angiotensin II↗

[Percutaneous rotational osteoclasis in management of congenital radio-ulnar synostosis].

PURPOSE OF THE STUDY: Congenital radio-ulnar synostosis blocks the wrist in a position of more or less pronounced pronation. The degree of pronation and possible bilateral involvement can compromise upper limb function. We propose percutaneous osteoclasis of the antebrachial skeleton to remedy this situation PATIENTS AND METHODS: We performed 12 percutaneous rotation osteoclasis procedures. The objective was to weaken the metaphysodiaphyseal cortical periosteum of one or both of the forearm bones by intermittent perforations. This enabled derotation of the wrist which was maintained for six to eight weeks in a brachiopalmar cast. RESULTS: Mean correction of pronation was 51 degrees. There were no cases of vascular or nervous complications and healing was uneventful. The esthetic outcome was very satisfactory. DISCUSSION: Surgery is not indicated for all cases of synostosis. We retain for surgery patients presenting pronation at 60 degrees or more. At this degree of pronation, function is greatly compromised in adolescence, particularly if there is a bilateral involvement. Compared with other techniques, percutaneous osteoclasis is a simple safe and reliable technique. Reoperation is not required to remove material. The procedure is easier in young children, preferably at the age of 3 to 7 years, before the development of a functional handicap.

Abnormalities, Multiple↗