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Time course of naloxone-precipitated withdrawal after acute methadone exposure in humans.

This study examined naloxone-precipitated withdrawal symptoms from 24 to 168 h after pretreatment with a single 30-mg i.m. dose of methadone in 6 male subjects who were experienced users of opioid drugs but were not currently dependent. The study showed that acute physical dependence signs and symptoms could be reliably precipitated with a small dose of naloxone (0.75 mg/70 kg i.m.) for as long as 96 h (4 days) after a single dose of methadone. The intensity of symptoms at 24 h post-methadone was similar to that observed at 96 h; no precipitated withdrawal effects were observed at 168 h (7 days) after methadone administration. The magnitude of precipitated withdrawal effects at 96 h was not attenuated by the administration of a prior naloxone challenge at 24 h post-methadone. Agonist effects (pupillary constriction; subjective effects) were detectable at 24 h but not at 96 h post-methadone. The results suggest that methadone engenders long-lasting physical dependence effects that can be detected beyond the dissipation of acute agonist effects. Methadone pretreatments may provide a convenient mechanism for the production and examination of long-term mu-opiate receptor physical dependence.

Adult↗

Comparison of extraction and precipitation methods for the HPLC determination of furosemide in plasma and urine.

Comparisons have been made between an ether extraction method and an acetonitrile precipitation method for the HPLC determination of furosemide (frusemide) in human plasma and urine. Recoveries of furosemide were 81-89% (ether extraction method for plasma), 73-103% (acetonitrile precipitation method for plasma) and 62-89% (ether extraction method for urine) for the concentration ranges studied. Values of correlation coefficients were 0.9998, 0.9991 and 0.9997 for standard curves for the three methods, respectively. Accuracy and precision (RSD) were: 92.4-114% +/- 3.57-20% for ether-extracted plasma; 98.1-103% +/- 3.47-19.9% for acetonitrile-precipitated plasma; and 103-107% +/- 4.03-13.2% for ether-extracted urine. Because of carryover of endogenous urine components, the acetonitrile-precipitation assay was unacceptable for urine. Furosemide was stable in frozen plasma for at least 113 days and in frozen urine for at least 204 days. No artifactual appearance of the hydrolysis product of furosemide, 4-chloro-5-sulfamoylanthranilic acid (CSA), was detected by the ether-extraction method under normal assay conditions.

Journal Article↗

A 64 kDa antigen/glutamic acid decarboxylase (GAD) in fetal pig pro-islets: co-precipitation with a 38 kDa protein and recognition by T cells in humans at risk for insulin-dependent diabetes.

The development of insulin-dependent diabetes mellitus (IDDM) is associated with circulating antibodies to a pancreatic islet protein of MW 64,000 (64 kDa), reported to be glutamic acid decarboxylase (GAD). To investigate the antigenic properties of the 64 kDa antigen/GAD in IDDM we employed fetal pig pro-islets, a convenient source of islet antigens and an alternative to adult human islets for transplantation. Pro-islets contained a 64 kDa protein precipitated by antibodies in the sera of 9/14 (64%) at-risk IDDM, 12/33 (36%) recent-onset IDDM and 4/12 (33%) established IDDM patients and in 1/18 (5%) healthy control subjects. In addition, a 38 kDa protein was co-precipitated with the 64 kDa protein by 6/14 (43%) at-risk IDDM, 5/33 (12%) recent-onset IDDM, 1/12 (8%) established IDDM patient sera and 1/18 (5%) control subject serum. Both 64 kDa and 38 kDa antigens were specific to pro-islets; neither was detected in fetal pig thyrocytes, hepatocytes or splenocytes. The majority of the 64 kDa protein was co-precipitated with GAD enzymatic activity from pro-islets by either IDDM sera or a sheep anti-GAD serum. Previously, we showed that peripheral blood mononuclear cells (PBMC) from over half the subjects defined as being at risk for IDDM proliferate in response to fetal pig pro-islets. Proliferative responses of PBMC from pre-diabetic subjects to a crude extract of pro-islets were therefore measured before and after depletion of GAD by adsorption of the extract against GAD-1 monoclonal antibody. In 5/10 at-risk subjects, T cell stimulation indices were greater than the control mean + 2 SD and decreased in four by > 50% after depletion of GAD. In summary, a 64 kDa protein with the properties of GAD is present in fetal pig pro-islets and is recognized by both antibodies and T cells in a significant proportion of subjects at risk for early IDDM. Some subjects with anti-64 kDa antibodies also have antibodies that co-precipitate a 38 kDa pro-islet protein. Prospective studies of T cell reactivity in at-risk IDDM subjects are required to delineate the role of GAD and other candidate autoantigens in the initiation and progression of beta cell destruction.

Adolescent↗

Immunofixation reveals an apparent alpha heavy chain caused by precipitation of fibrinogen with IgA antiserum.

BACKGROUND: Fibrinogen present in serum specimens can interfere with the interpretation of serum protein electrophoresis. We report here the unexpected precipitation of fibrinogen by an IgA antiserum used in immunofixation electrophoresis. METHODS: Immunofixation electrophoresis of plasma combined with ethanol precipitation, serial dilution of plasma, and fibrinogen adsorption of the antiserum were used to investigate the apparent immunoreactivity of a commercial source of IgA antiserum to fibrinogen. RESULTS: Fibrinogen immunoreactivity by IgA antiserum was observed at fibrinogen concentrations > or =0.93 g/l. Ethanol precipitation of plasma removed fibrinogen and prevented the immunofixation of the protein by the IgA antiserum. Adsorption of the IgA antiserum with human fibrinogen removed its ability to precipitate fibrinogen, demonstrating cross-reactivity between the IgA antiserum and fibrinogen. CONCLUSIONS: Commercial sources of antiserum used for immunofixation electrophoresis may contain antibodies with specificity towards proteins typically absent from serum such as fibrinogen and can produce clinically misleading results.

Female↗

Adsorption of Acid Red 73 on copper dithiocarbamate precipitate-type solid wastes.

Three solid wastes, copper N,N'-bis(dithiocarboxy)piperazine ([CuBDP](n)), copper diethyldithiocarbamate (Cu(DDTC)(2)) and copper dimethyldithiocarbamate (Cu(DMTC)(2)), were prepared and tested as adsorbents to remove Acid Red 73 from wastewater. It was found that the three precipitates all could effectively adsorb the dye but their adsorption abilities were rather different. The maximum adsorption amounts of the coordination polymer precipitate [CuBDP](n) reached as high as 364mg g(-1), much greater than those of Cu(DDTC)(2) and Cu(DMTC)(2) (42.9 and 37.8mg g(-1), respectively). The investigation of adsorption models showed these adsorption processes followed the pseudo-second-order kinetic equation and the adsorption balances could be described with both Langmuir and Freundlich isotherms, but the latter seemed to be more suitable. Their adsorption nature was inferred to be physical adsorption and mainly depended on the hydrophobic interaction between these precipitates and Acid Red 73. This is the first example for the reutilization of metal dithiocarbamate precipitates as solid wastes to date.

Adsorption↗

SR 141716 (Rimonabant) precipitates withdrawal in marijuana-dependent mice.

Repeated marijuana use is known to lead to physical dependence in humans; however, its dependence liability has yet to be adequately assessed in laboratory animals. The goals of the present study were to: assess whether the CB(1) antagonist SR 141716 (rimonabant) precipitates withdrawal in mice that had been repeatedly exposed to marijuana smoke, and to compare these precipitated withdrawal effects to those elicited following intravenous administration of its chief psychoactive component Delta(9)-tetrahydrocannabinol (Delta(9)-THC). SR 141716 elicited a significant increase in paw tremors in mice that were repeatedly dosed with either marijuana or Delta(9)-THC. Unexpectedly, the blood and brain concentrations of Delta(9)-THC following marijuana exposure were considerably lower than those found following Delta(9)-THC injection when comparing an equivalent magnitude of paw tremors in both conditions. Finally, Delta(9)-THC dose-dependently alleviated SR 141716-induced paw tremors in marijuana-dependent mice, but marijuana itself failed to reverse the precipitated withdrawal effect. It is likely that marijuana exposure generated insufficient Delta(9)-THC brain levels (i.e., 203+/-19 ng/g) to reverse the withdrawal signs compared with the brain levels following intravenous injection (i.e., 1862+/-82 ng/g). These findings taken together indicate that mice exposed repeatedly to marijuana smoke exhibit similar precipitated withdrawal effects as Delta(9)-THC-injected mice.

Animals↗

The impact of volcanic gases from Miyake island on the chemical constituents in precipitation in the Tokyo metropolitan area.

The volcano on Miyake Island first erupted in July 2000 and continuous emission of volcanic gas from the collapsed caldera has been observed from the middle of August 2000. The large volcanic emission of SO2 had a strong influence on Tokyo metropolitan area, which is located approximately 150 km north of Miyake Island. We measured major ions in precipitation and dry deposition samples which had been collected at five sampling sites (Yokohama, Kashiwa, Fujisawa, Yokosuka, and Hachioji) in the Tokyo metropolitan area for 12 years since 1990. We have evaluated quantitatively the impact of the volcanic SO2 gas emitted from Miyake Island on the Tokyo metropolitan area by comparing depositional ionic constituents in the volcanic degassing period (from September 2000 to August 2001) with those in the normal period of the past 10 years (September 1990 to August 2000). nss-SO4(2-) concentrations in precipitation at the sampling sites in the Tokyo metropolitan area were 59.5-77.0 microeq/L during the degassing period, and 33.3-44.1 microeq/L during the normal period, respectively. The difference of nss-SO4(2-) concentrations between the two periods was statistically significant. In contrast, no significant differences were observed in the concentrations of the other major ions (NH4+, nss-Ca2+, Cl-, and NO3-) between the two periods. The impact of volcanic degassing from Miyake Island on the ionic concentrations in the precipitation of the Tokyo metropolitan area was seen only in the H+ and nss-SO4(2-) concentrations. The annual wet deposition amount of volcanic nss-SO4(2-) into the Tokyo metropolitan area has been quantitatively estimated. The annual wet deposition amounts were calculated as 701+/-277 Meq/year (22.4+/-8.9 kt SO2/year) on the total area of the Tokyo metropolitan area (14,000 km2). The wet deposition amount of nss-SO4(2-) corresponds to only 0.15% of the total annual amount of volcanic SO2 (15 Mt/year) emitted from Miyake Island from September 2000 to August 2001. This estimation is consistent with a previous study which reported that 0.3% of the atmospheric discharge of SO2 from the volcano in Mt. Etna in Sicily was deposited by precipitation to the surrounding area (1200 km2). The annual wet deposition amount of volcanic SO2 to the Tokyo metropolitan area was at the same order of the magnitude (37+/-15%) as the annual anthropogenic SO2 amount (60 kt/year) emitted from the Tokyo metropolitan area.

Air Movements↗

Imaging and characterization of fine gamma' precipitates in a commercial nickel-base superalloy.

Empirical datasets of volume fractions and size distributions of small gamma' precipitates from "real" multi-component engineering nickel-based superalloys are vital to calibrate and validate the computer models which predict high sensitivities of mechanical properties to size and volume fraction of these fine gamma precipitates, and in order to accelerate microstructure and alloy development. Consequently, we investigated a number of imaging techniques available in a Tecnai F-20 FEG/TEM and selected the technique which best enabled rapid and extensive acquisition of these datasets using the engineering alloy, René 88'DT. The EFTEM technique was found to be the most appropriate method for imaging fine gamma' precipitates while further investigation showed that the Cr-M-edge, in comparison with other ionization-edges provided the best images based largely on contrast-to-noise ratio. Imaging of the Cr-M-edge elemental maps were further improved by investigating the effects of microscope parameters, imaging filter parameters and analysis of the experimental electron energy loss spectra obtained from this alloy. In addition, a novel technique to determine the volume fraction of the fine gamma' precipitates without the need to determine the absolute thickness of the TEM foil is proposed.

Journal Article↗

Precipitating factors and decision-making processes of short-term worsening heart failure despite "optimal" treatment (from the IN-CHF Registry).

This study sought to prospectively assess which factors were related to short-term worsening heart failure (HF) leading to or not to hospital admission, in long-term outpatients followed by cardiologists. The subsequent decision-making process was also analyzed. The study population consisted of 2,701 outpatients enrolled in the registry of the Italian Network on Congestive Heart Failure (IN-CHF) and followed by 133 cardiology centers (19% of all existing Italian cardiology centers). Clinical and follow-up data were collected by local trained clinicians; 215 patients (8%) had short-term decompensation (on average 2 months after the index outpatient visit). Multivariate analysis showed that previous hospitalization, long duration of symptoms, ischemic etiology, atrial fibrillation, higher functional class (New York Heart Association classification III to IV), higher heart rate, and low systolic blood pressure were independently associated with HF destabilization. Poor compliance (21%) and infection (12%) were the most frequent precipitating factors, but a precipitating factor was not identified in 40% of the patients. Poor compliance was more common in women, but no other clinical characteristics emerged as being related with a specific precipitating factor. Fifty-seven percent of the patients with a short-term recurrence of worsening HF required hospital admission; infusion treatment with inotropes and/or vasodilators was necessary in 19% of them. Long-term therapy was changed in 48% of the patients. Thus, in ambulatory HF patients, short-term worsening HF can be predicted according to the clinical characteristics on an outpatient basis. Nearly 1/3 of precipitating factors can be prevented. Patient education and avoidance of inappropriate treatment may reduce the number of relapses.

Aged↗

Comparison of manual methods of determination of albumin in human cerebrospinal fluid by the bromcresol green and immuno-precipitation methods.

Simultaneous determinations of albumin concentrations in human cerebrospinal fluid were made by three different manual methods: bromcresol green dye-binding technique of Doumas et al., a modification of the latter with color measurement shortly after the addition of dye as proposed by Ingwersen and Raabo and finally by an immuno-precipitation technique. Results obtained by the immuno-precipitation method correlated significantly with the dye-binding method of Doumas et al., (r = 0.93) and the procedure of Ingmersen and Raabo (r = 0.94). Data from the two dye-binding techniques correlated significantly with one another also (r = 0.98). However, the immuno-precipitation technique gives albumin values lower than the dye-binding procedures. The latter presumably estimates other proteins which can also bind bromcresol green. The data corroborates the conclusions of earlier investigators that immuno-precipitation method is more specific for albumin assays.

Adult↗

Separation of steroid compounds by overloaded preparative chromatography with precipitation in the fluid phase.

In order to gain a commercially acceptable yield compared to the adsorption capacity of the column, a rather large amount of sample is separated with preparative chromatography. During the competitive adsorption of the sample-components, the species adsorbing better can force the rest out of the adsorbent phase. As a consequence, the concentrations of the later components may increase in the fluid phase to a level that those species start to precipitate. A mathematical model which takes the precipitation and dissolution into consideration is presented in this paper. Data calculated by this model are compared to that we obtained by using a previous mathematical model as well as the experimental results gained by a laboratory scale separation of steroid compounds on an organic polymer adsorbent. The equilibrium adsorption-desorption and equilibrium precipitation-dissolution is the first approximation of the complicated process mentioned above. In our next publication we are to extend the model with kinetic terms belonging to adsorption-desorption and precipitation-dissolution process respectively.

Adsorption↗

Lack of sex differences in anxiety behaviors during precipitated benzodiazepine withdrawal in rats.

Nonprecipitated benzodiazepine (BZ) withdrawal has been reported to increase anxiety levels in rats. The present experiment determined if gender or hormonal status would modulate putative changes in anxiety-related behaviors during precipitated BZ withdrawal in rats. Intact and gonadectomized male and female rats were treated for 4 weeks with empty or diazepam (DZ)-filled silastic capsules. Animals were injected with the BZ antagonist flumazenil (RO15-1788; 5 mg/kg, i.p.) or vehicle, and immediately placed on the elevated plus-maze. Following the 10-min behavioral test, rats were decapitated and trunk blood was collected to measure corticosterone and gonadal hormone levels. During precipitated BZ withdrawal rats showed significantly decreased percent open-arm time; however, this finding was confounded by a significant decrease in activity levels (e.g., closed-arm entries and total-arm entries). Precipitated BZ withdrawal did not significantly attenuate percent open-arm entries, which factors out drug-induced changes in activity levels, compared to vehicle control animals. Overall, the results of this experiment suggest that precipitated BZ withdrawal does not significantly increase anxiety levels when compared to control animals.

Animals↗

Anxiogenic-like effects of spontaneous and naloxone-precipitated opiate withdrawal in the elevated plus-maze.

Withdrawal from opiates and other drugs of abuse in human addicts is associated with a state of anxiety that may be of motivational relevance for the maintenance of drug addiction. Previous attempts with rats to model the anxiogenic-like effects of opiate withdrawal using the elevated plus-maze have met with mixed success. The current study sought to determine whether spontaneous and naloxone-precipitated opiate withdrawal could be observed reliably in rats made dependent on morphine through implantation of two morphine pellets (75 mg morphine base each). Seventy-two hours after implantation of either morphine or placebo pellets, rats were tested in the elevated plus-maze. In Experiment 1, pellets were removed 8 or 12 h prior to test; results indicated an anxiogenic-like effect (reduction in time spent in the open arms) of opiate withdrawal at 8 but not 12 h postpellet removal. In Experiment 2, pellets were not removed, but withdrawal was precipitated with naloxone (0.003-0.03 mg/kg s.c.). Naloxone dose dependently precipitated a reduction in exploration of the open arms of the plus-maze. The results suggest that both spontaneous and precipitated withdrawal from continuous morphine administration via pellet implantation result in demonstrable anxiogenic-like effects in the plus-maze.

Animals↗

Thermodynamics of ions precipitation in mixed-solvent mixtures

A framework derived from thermodynamic principles of solid-liquid equilibrium criteria was formulated to correlate and predict the precipitation of salts from aqueous solutions using organic solvents. The activity coefficient of a given salt in a mixed-solvent mixture was related to the activity coefficients of such a salt in each of the pure solvents (water and organic) using the excess Henry's constant approach (H(i)(E)). The Wohl's expansion was then employed to model the excess Gibbs free energy (g(E)) function. Two equations were provided; the two-suffix equation, and the three-suffix equation. A previously acquired precipitation database was used to evaluate the correlative ability of the framework equations. The precipitation measurements were adequately correlated and predicted by the two interaction parameters equation; the two-suffix equation. However, the three-suffix equation, with three interaction parameters, was more accurate. The regressed interaction parameters can be used as predictive tools to estimate the precipitation fractions (P) for the tested systems for which no experimental data are available. Furthermore, such parameters can be employed to predict the solubilities of the tested salts in the organic solvent.

Journal Article↗

A comparison of antagonist-precipitated withdrawal under anesthesia to standard inpatient withdrawal as a precursor to maintenance naltrexone treatment in heroin users: outcomes at 6 and 12 months.

To compare two methods of heroin withdrawal, 51 heroin users were randomised to undergo a 1 day precipitated withdrawal procedure using naloxone under anaesthetic. About 50 participants were randomised to receive the current standard inpatient withdrawal treatment using clonidine plus symptomatic medication. Following withdrawal, both groups were offered 9 months of naltrexone treatment and supportive counselling. Outcome measures were: commencement of naltrexone, retention in treatment and heroin use at 6 and 12 months. Significantly more of the precipitated withdrawal group completed withdrawal, commenced naltrexone and stayed in treatment for the first 3 months. Overall, there was a significant reduction in both self-reported heroin use and morphine concentration in hair over the 12 month study period, with participants in the precipitated withdrawal group showing significantly lower morphine concentration at 6 months. Being younger and having a lower level of dependence were predictors of abstinence at 6 and 12 months. The advantage of precipitated withdrawal under anesthesia did not persist beyond 3 months with respect to retention in naltrexone treatment or beyond 6 months with respect to heroin use. Long-term follow-up is crucial in assessing the effects of treatment interventions for heroin dependence.

Adrenergic alpha-Agonists↗

Precipitating factors and life events in serious suicide attempts among youths aged 13 through 24 years.

OBJECTIVE: Precipitating factors and life events associated with medically serious suicide attempts were examined in young people making serious suicide attempts and control subjects. METHOD: Using a case-control design, the authors contrasted 129 young people making serious suicide attempts with 153 randomly selected community controls on a series of life event occurrences within the preceding year. Precipitating factors for serious suicide attempts were also examined. RESULTS: The most common precipitants of serious suicide attempts were relationship breakdowns, other interpersonal problems, and financial difficulties. However, one third of those attempting suicide were unable to describe any precipitating factor. Individuals who made serious suicide attempts had elevated rates of life events which were associated principally with interpersonal difficulties, work issues, financial difficulties, and legal problems. When due allowance was made for intercorrelations between life event measures and antecedent social, family, and personality factors, interpersonal losses and conflicts and legal problems remained significant risk factors for serious suicide attempts. CONCLUSIONS: Important proximal occurrences for serious suicide attempts among young people include a series of life events associated principally with interpersonal conflicts, relationship difficulties, and legal problems.

Adolescent↗

Physicochemical properties of amorphous precipitates of cimetidine-indomethacin binary system.

We have found that the binary system, consisting of a precipitate of cimetidine and naproxen, became amorphous due to intermolecular interaction. In order to clarify the interaction between cimetidine and other drugs, the physicochemical properties of binary systems consisting of cimetidine and drugs, phenacetin, salicylamide or indomethacin, were investigated. X-ray powder diffraction patterns and thermal analysis findings for the precipitates indicated that the cimetidine-indomethacin system has an amorphous structure, whereas the cimetidine-phenacetin and cimetidine-salicylamide systems do not. Fourier-transform infra-red (FTIR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy findings suggested that there is an intermolecular interaction between a proton in the imidazole ring of cimetidine and the C=O in the COOH of indomethacin. Since an interaction by the hydrogen bond between cimetidine and indomethacin would prevent three-dimensional arrangements of the molecules, the precipitate would be amorphous. In the cimetidine-indomethacin system, decarboxylation of indomethacin occurred below the melting temperature, indicating that the chemical stability decreased upon precipitation. Cimetidine was found to interact with drugs with a carboxyl group. The interaction would be applicable to make the amorphous system of the drugs and increase the solubility of the drugs.

Anti-Inflammatory Agents, Non-Steroidal↗

Precipitate crystal structure determination in melt spun Mg-1.5wt%Ca-6wt%Zn alloy.

A melt-spun Mg-1.5%wtCa-6wt%Zn alloy was analyzed by means of transmission electron microscopy, energy dispersive X-ray spectroscopy, and scanning transmission electron microscopy. The as-solidified alloy exhibited both spherical matrix precipitates and elongated precipitates at the grain boundaries (grain-boundary films). After heat treatment, the alloy showed faceted precipitates (cuboidal shape), mostly on dislocations. It was found that the observed precipitates are the same compound, Ca2Mg6Zn3. As there was no crystallographic data for this compound in the literature, its crystal structure was investigated by comparison of experimental and simulated selected-area electron-diffraction patterns and high-resolution electron microscopy images. This study indicated that Ca2Mg6Zn3 is a trigonal compound with space group P 3 1c and lattice parameters a = 0.97 nm, c = 1.0 nm.

Alloys↗