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PubMed2001

How do trigger factors acquire the capacity to precipitate headaches?

This study tested two contrasting theories of how trigger factors acquire the capacity to precipitate headaches. The sample consisted of 110 participants, of whom 48 suffered from regular headaches. Participants were exposed to a validated headache trigger factor for one of five exposure durations. The trigger used was "visual disturbance" (flicker, glare and eyestrain) induced by a very bright, stroboscopic light. Response to the stimulus was measured by participant ratings of the degree of visual disturbance and head pain caused by the stimulus. As expected, the headache sufferers experienced more visual disturbance and head pain in response to the stimulus than the non-headache individuals. Longer exposure to the stimulus was associated with a subsequent reduction in pain ratings in response to the stimulus. This desensitization effect supported an avoidance model of how trigger factors acquire the capacity to precipitate headaches. The findings of this study have implications for the etiology of headache disorders. Also, the findings imply that the traditional clinical advice that the best way to prevent migraine and headache is to avoid the factors that trigger them, may be counterproductive, as any short-term gains may be more than wiped out by decreased tolerance for the trigger factors.

Adult↗

PubMed2001

Changes in the expression of glial glutamate transporters in the rat brain accompanied with morphine dependence and naloxone-precipitated withdrawal.

The expression of mRNAs for the glial glutamate transporters, GLT-1 and GLAST, in the rat brain accompanied with morphine dependence and naloxone-precipitated withdrawal was investigated by Northern blot analysis. The expression of GLT-1 mRNA was significantly decreased in the striatum and thalamus of morphine-dependent rats, and significantly increased in the striatum 2 h after the naloxone-precipitated withdrawal, compared with that of naive rats. On the other hand, there were no significant changes in GLAST mRNA level in any brain region. These results suggest the involvement of GLT-1 in the development of morphine dependence and the expression of morphine withdrawal.

ATP-Binding Cassette Transporters↗

PubMed1997

Increased release of excitatory amino acids in rat locus coeruleus in kappa-opioid agonist dependent rats precipitated by nor-binaltorphimine.

Extracellular fluid levels of glutamate and aspartate in the locus coeruleus (LC) during nor-binaltorphimine (nor-BNI)-precipitated withdrawal from butorphanol, (5alpha,7alpha,8beta)-(+)-N-methyl-N-[7-(1-pyrrolidiny l)-1-oxaspiro [4,5] dec-8-yl]-benzeneacetamide (U-69,593), or morphine were measured in rats. When the microdialysis probe was located in the core of the LC, increases in glutamate and aspartate were noted after nor-BNI (48 nmol/50 microl, LC)-precipitated withdrawal in rats that had been intracerebroventricularly infused with butorphanol (26 nmol/1 microl/h) or U-69,593 (26 nmol/10 microl/h) for 3 days. The glutamate and aspartate levels in the LC markedly increased in the butorphanol- or U-69,593-dependent rats within 60 min following administration of nor-BNI. However, there was no significant increase in levels of glutamate, and only a slight increase in levels of aspartate, after nor-BNI treatment of the morphine (26 nmol/1 microl/h)-infused rats. Behavioral signs of withdrawal (teeth-chattering, wet-dog shakes, etc.) were observed following nor-BNI challenge in the butorphanol- or U-69,593-infused rats, with only minimal signs in the morphine-infused rats, and none in the saline-infused controls. These results directly suggest that kappa-opioid receptors and excitatory amino acids within the LC mediate withdrawal in animals dependent on butorphanol or U-69,593, but not on morphine.

Animals↗

PubMed1991

Interactions of concanavalin A with glycoproteins. A quantitative precipitation study of concanavalin A with the soybean agglutinin.

Certain oligomannose-type glycopeptides have been previously shown to be bivalent for binding to concanavalin A and capable of precipitating the lectin by forming homogeneous cross-linked lattices [L. Bhattacharyya, M. I. Khan, and C.F. Brewer, Biochemistry, 27 (1988) 8762-8767]. In the present study, the effect of protein environment on the binding properties of an oligomannose-type oligosaccharide has been examined through quantitative precipitation analysis of the interactions of concanavalin A (Con A) with the soybean (Glycine max) agglutinin (SBA), which is a tetrameric glycoprotein possessing a single Man9-oligomannose chain per monomer. The results showed that SBA forms two different types of cross-linked complexes with tetrameric Con A, depending on the relative ratio of the two molecules in solution. At a concentration of one equivalent or less, SBA forms a 1:1 complex with Con A. At concentrations exceeding one equivalent, SBA forms a 2:1 complex with Con A. However, SBA forms only 1:1 cross-linked complexes with dimeric forms of Con A, such as acetyl- and succinyl-Con A. The results demonstrated that the total valency of the carbohydrate of SBA is a function of both the quaternary structure of Con A, as well as the relative ratio of SBA to Con A. In addition, the individual Man9-oligosaccharide, which as a glycopeptide is bivalent for binding to Con A, expresses univalency when present on the protein matrix of SBA.

Carbohydrate Sequence↗

PubMed1984

Comparison of phosphotungstate and dextran sulfate-Mg2+ precipitation procedures for determination of high density lipoprotein cholesterol.

Because of the controversy over the best method for assaying high density lipoprotein (HDL) cholesterol in the clinical laboratory, a commonly used phosphotungstate method for precipitating low density and very low density lipoproteins (LDL and VLDL) was compared with a recently recommended dextran sulfate precipitation method. The accuracy and precision of HDL cholesterol determinations were similar for both methods. Either of these procedures would appear to be equally satisfactory for the assay of HDL cholesterol in the clinical laboratory.

Apolipoprotein A-I↗

PubMed1996

Diltiazem inhibits naloxone-precipitated and spontaneous morphine withdrawal in rats.

The effects of diltiazem, a Ca2+ channel blocker, on naloxone-precipitated and spontaneous morphine withdrawal were studied in male Sprague-Dawley rats. In naloxone-precipitated withdrawal, body weight loss and plasma corticosterone elevation were dose dependently inhibited by diltiazem injected 4 or 2 and 4 h before naloxone, respectively. Three administrations of diltiazem (17, 11 and 5 h before naloxone) did not reduce the above withdrawal signs. Diarrhea was dose dependently inhibited by all schedule of diltiazem treatments. In spontaneous withdrawal, body weight loss and plasma corticosterone elevation were dose dependently inhibited by two (6 and 12 h) or three (6, 12 and 18 h after the last morphine) treatments with diltiazem at 6-h intervals after the last morphine, but not by a single diltiazem injected 18 h after the last morphine.

Animals↗

PubMed1999

Mecamylamine-precipitated nicotine-withdrawal aversion in Lewis and Fischer 344 inbred rat strains.

Many studies have indicated that Lewis and Fischer 344 inbred rat strains show marked differences in behavioral responses to abused drugs. In the present study, we sought to determine whether these two strains of rats show different responses in mecamylamine-precipitated nicotine-withdrawal aversion using the conditioned place preference paradigm. Rats were treated subcutaneously with 10 mg/kg/day nicotine for 7 days using an osmotic minipump. After chronic nicotine infusion, the nicotinic receptor antagonist mecamylamine produced a significant place aversion in Lewis, but not in Fischer 344 rats. These results suggest that mecamylamine-precipitated nicotine-withdrawal aversion is strongly regulated by genetic factors.

Animals↗

PubMed1997

Inhibitory effect of agmatine on naloxone-precipitated abstinence syndrome in morphine dependent rats.

Effects of agmatine, which is an endogenous polyamine metabolite formed by decarboxylation of L-arginine, were investigated on the morphine abstinence syndrome in rats. Two pellets containing 75 mg morphine base (total 150 mg) were implanted subcutaneously on the back of rats. Seventy-two hours after morphine implantation, agmatine sulphate (20, 30 and 40 mg/kg) or saline was injected intraperitoneally. Forty-five min later, naloxone (2 mg/kg) was injected intraperitoneally to induce precipitated withdrawal. Immediately after naloxone injection, rats were observed for 15 min, and abstinence syndrome signs, which included jumping, wet dog shake, writhing, defecation, ptosis, teeth chattering and diarrhea were counted or rated. Agmatine attenuated all of the signs of the morphine abstinence syndrome dose dependently and significantly. Our results suggest that agmatine prevents naloxone-precipitated abstinence syndrome in morphine dependent rats; thus, this drug may be beneficial in the treatment of opioid dependence.

Agmatine↗

PubMed1986

Directed intravascular precipitation of bisantrene for pelvic malignant lesions: preclinical studies.

Bisantrene, a clinically active anticancer drug with limited solubility at physiologic pH, was delivered by selective injection into the internal iliac artery of male calves. The percutaneous transfemoral angiographic techniques used in the calves were identical to those used in adult human patients. Directed intravascular precipitation of bisantrene at the maximal tolerable clinical dose for intravenous administration (260 mg/m2) caused severe tissue damage in 5 of 10 animals that received these intra-arterial injections. (One calf in this study group died of unknown causes 10 days after the drug infusion). A reduced intra-arterial dose (50 mg/m2) was used in seven calves, and no local tissue damage was evident on gross or microscopic examination. Nevertheless, resultant concentrations of bisantrene deposited in the ipsilateral bladder wall were 10- to 100-fold those concentrations found after intravenous administration of a dose 5 times higher. These animal toxicology and pharmacology data support initiation of a phase I clinical trial of directed intravascular precipitation of bisantrene in humans. This clinical trial will be developed for patients with advanced refractory cancers of the anatomic true pelvis, such as those originating in the urinary bladder, prostate, rectum, and uterine cervix.

Angiography↗

PubMedDate not supplied

Alum-precipitated autoclaved Leishmania major plus bacille Calmette-Guérrin, a candidate vaccine for visceral leishmaniasis: safety, skin-delayed type hypersensitivity response and dose finding in healthy volunteers.

In a previous efficacy study, autoclaved Leishmania major (ALM) + bacille Calmette-Guérrin (BCG) vaccine was shown to be safe, but not superior to BCG alone, in protecting against visceral leishmaniasis. From June 1999 to June 2000, we studied the safety and immunogenicity of different doses of alum-precipitated ALM + BCG vaccine mixture administered intradermally to evaluate whether the addition of alum improved the immunogenicity of ALM. Twenty-four healthy adult volunteers were recruited and sequentially allocated to receive either 10 microg, 100 microg, 200 microg, or 400 microg of leishmanial protein in the alum-precipitated ALM + BCG vaccine mixture. Side effects were minimal for all doses and confined to the site of injection. All volunteers in the 10 microg, 100 microg, and 400 microg groups had a leishmanin skin test (LST) reaction of > or = 5 mm by day 42 and this response was maintained when tested after 90 d. Only 1 volunteer out of 5 in the 200 microg group had a LST reaction of > or = 5 mm by day 42 and the reasons for the different LST responses in this group are unclear. This is the first time that an alum adjuvant with ALM has been in used in humans and the vaccine mixture was safe and induced a strong delayed type hypersensitivity (DTH) reaction in the study volunteers. On the basis of this study we suggest that 100 1 microg of leishmanial protein in the vaccine mixture is a suitable dose for future efficacy studies, as it induced the strongest DTH reaction following vaccination.

Adult↗

PubMed2000

Acidic and alkaline precipitation in the Cilician Basin, north-eastern Mediterranean Sea.

Samples from precipitation events collected at Erdemli during February 1996-June 1997 were analyzed to determine their particulate aluminium content, in addition to pH and conductivity measurements. Backward air mass trajectories corresponding to the rainy days were analyzed to determine potential source regions of acidic and alkaline constituents transported to the Cilician Basin. Approximately 28% of the rain samples were found to be acidic and the trajectories associated with half of the acid precipitation events were from the Mediterranean Basin and the Balkan Peninsula, while the other half were from the Anatolian mainland and local sources. Rain samples were found to be alkaline (58%), with their trajectories originating from North Africa and the Middle East. As a result of its CaCO3 content, mineral dust from these arid regions significantly increased the pH of rainwater.

Acid Rain↗

PubMed2000

Precipitated and spontaneous withdrawal following administration of lorazepam but not zolpidem.

Radiotelemetry was utilized to compare zolpidem and lorazepam tolerance and withdrawal in rats. Locomotor activity, electromyographic activity (EMG), and body temperatures were used to assess the acute drug effects, and as measures of tolerance and withdrawal. Lorazepam, zolpidem, or vehicle was administered for 12 days, and data were recorded daily, immediately, after treatment. Data were also recorded immediately after flumazenil (25 mg/kg, IP) precipitated withdrawal and during 4 days of spontaneous withdrawal. Complete tolerance to the acute effects of lorazepam administration developed within 7 days of treatment and both flumazenil-precipitated and spontaneous withdrawal were observed. In contrast, there was no tolerance to the sedative actions of zolpidem administration after 12 days, but complete tolerance to the hypothermic and muscle relaxant effects was apparent after 8 days of treatment. Despite the presence of tolerance, no evidence of either spontaneous or flumazenil-induced withdrawal was recorded in these rats. In conclusion, this model suggests that as a sedative zolpidem has significant advantages over the classic benzodiazepines.

Animals↗

PubMed1997

Conditioned sucrose aversions produced by naloxone-precipitated withdrawal from acutely administered morphine.

The aversive properties of acute naloxone-precipitated morphine withdrawal were examined in the taste reactivity paradigm. Acute naloxone-precipitated withdrawal paired with sucrose solution established conditioned active rejection of the sucrose solution. Active rejection of sucrose was observed when naloxone was administered both 1 h and 22 h after morphine. When the stimulus properties of morphine were present during the conditioning trial, the conditioned sucrose aversion was only expressed when the rats were tested in the same drug state in which they had learned the aversion. However, when the stimulus properties of morphine were not present during conditioning, the aversion was expressed in the absence of the morphine state. The results suggest that palatability shifts can be conditioned to sucrose paired with acute morphine withdrawal.

Animals↗

PubMed1997

Nicotine abstinence syndrome precipitated by central but not peripheral hexamethonium.

A rodent model of nicotine dependence has been developed based on continuous subcutaneous (s.c.) infusion of nicotine tartrate. Nicotine abstinence syndrome was precipitated by s.c. injection of the nicotinic antagonist mecamylamine, which freely crosses the blood-brain barrier. In contrast, the nicotinic antagonist hexamethonium crosses the blood-brain barrier very poorly. This study determined whether central or peripheral administration of hexamethonium could precipitate nicotine abstinence. In the first experiment, 26 nicotine-dependent rats were injected s.c. with 0.5, 5 or 10 mg/kg hexamethonium dichloride or saline alone and observed for 20 min. Few abstinence signs were observed in any group; there was no significant drug effect. In the second experiment, 18 rats were cannulated in the third ventricle and rendered nicotine dependent. One week later, rats were injected through the cannula with 12 or 18 ng hexamethonium or saline alone and observed for 20 min. Both dose groups differed significantly from the saline-injected group, and there was a significant positive linear trend of signs as a function of dose. The high dose had no significant effect in 14 nondependent rats. We conclude that hexamethonium is much more potent by the central route, and there is a major central nervous system component in nicotine dependence.

Animals↗

PubMed1998

Naloxone-precipitated morphine withdrawal induced place aversions: effect of naloxone at 24 hours postmorphine.

The aversive properties of naloxone-precipitated withdrawal from acutely administered morphine were assessed using the place-conditioning paradigm. The conditioned place aversion produced by naloxone (0.5-1.0 mg/kg, s.c.) after two conditioning trials was enhanced by pretreatment with morphine (20 mg/kg, s.c.) 24 h prior to the conditioning trial. Naloxone precipitated withdrawal from acutely administered morphine produces an aversive motivational state that becomes associated with place cues.

Analysis of Variance↗

PubMed2001

Study of precipitant systems by computerised simulation. Influence of optical elements on the noise associated with the transmittance.

The transmittance signal of a precipitant system measured with a focused laser beam carries associated noise coming from several sources. In this work, we have studied the influence of the focal parameters (wavelength, focal length and prefocused radius of the beam) on the maximum noise reached in equivalent nucleation processes. For this purpose, a simulation program of precipitating systems, designed in FORTRAN 90, has been developed. The program generates simulated transmittances, which are processed by another computer program to extract associated noise. Wide ranges of values of the focal parameters have been analysed, finding relationships between the maximum noise and the focal parameters. They have been justified in connection with the changes observed in the radial parameters, which define the size and shape of the focused path.

Journal Article↗

PubMed1980

Controlled trial of an electrostatic precipitator in childhood asthma.

A cross-over trial was conducted on 10 children with moderate to severe asthma, who had positive skin tests to Dermatophagoides pteronyssinus and nocturnal wheeze. An electrostatic precipitator was used during the night to remove airborne particles from the bedroom. During use of the precipitator peak expiratory flow rates were no better than in a control period.

Adolescent↗

PubMed2000

Reversibly soluble biocatalyst: optimization of trypsin coupling to Eudragit S-100 and biocatalyst activity in soluble and precipitated forms.

Eudragit S-100, a copolymer of methacrylic acid and methyl methacrylate is soluble at pH above 5 and insoluble at pH below 4.5. pH-dependent solubility of the polymer is used for the development of reversibly soluble biocatalyst, which combines the advantages of both soluble and immobilized biocatalysts. Activity of trypsin, covalently coupled to Eudragit S-100, was improved by protecting the active site of the enzyme with benzamidine and removing the noncovalently bound proteins with Triton X-100 in 0.15 M Tris buffer (pH 7.6). Accurate choice of coupling conditions combined with proper washing protocol produced highly active enzyme-polymer conjugate with no noncovalently bound protein. Two conjugates with 100-fold difference in the content of trypsin coupled to Eudragit S-100 were studied when the preparations were in soluble and precipitated forms. The K(m)values of the soluble enzyme to the lower molecular weight substrate was less than that of the free enzyme, whereas that to the higher molecular weight substrate was closer to that of the free enzyme. Activities of the soluble and precipitated immobilized trypsin with higher molecular weight substrate were completely inhibited by soy bean trypsin inhibitor, whereas complete inhibition with soy bean trypsin inhibitor was never achieved with lower molecular weight substrate, indicating reduced access of high-molecular weight substrate/inhibitor to some of the catalytically active enzyme molecules in trypsin-Eudragit conjugate.

Journal Article↗