Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
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Recent reports have suggested that spike-like pseudopods develop on platelets loaded with intracellular chelating agents during glass activation, and proposed that the extensions are caused by an unusual organization of newly assembled actin filaments. The present study has reexamined this hypothesis. Platelets loaded with one of the chelating agents, Quin II or BAPTA, seldom formed spike-like pseudopods when exposed to glass at 37 C for 30-60 min. However, when chilled and rewarmed the Quin II-or BAPTA-loaded platelets readily developed one or several spike-like extensions after a 30-60-min exposure to glass or on shaking in suspension. Thin section and negative-stain electron microscopy demonstrated that the major constituents of spike-like pseudopods were microtubules. Unusual coils of actin filaments were not observed. The observation was confirmed by immunofluorescence microscopy employing an anti-tubulin antibody and fluorescein-conjugated antimouse IgG. Cytochalasin B, an agent that inhibits new actin filament formation had virtually no effect on spike formation by chilled-rewarmed, Quin II- or BAPTA-loaded cells, whereas prior exposure to vincristine, an agent that dis-assembles microtubules and prevents their reformation, blocked spike development. Taxol, a drug that stabilizes microtubules and prevents their disassembly by cold or vincristine, prevented spike formation. Results indicate that microtubule assembly is the major cause of spike-like pseudo-pod formation, and the increased assembly may be due to binding of free cytoplasmic calcium by intracellular chelating agents.
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PMID:Influence of intracellular chelating agents on formation of spike-like pseudopods by human platelets. 1680 Oct 87

The anti-snake venom activities of the methanolic extract of the bulb of Crinum jagus plant (Amaryllidaceae) were investigated in vitro and in vivo against the venoms of three notable snake species: Echis ocellatus, Bitis arietans and Naja nigricollis. The extract was prepared by cold marceration in 50% methanol at 37 degrees C with intermittent shaking for 48 h. An yield of 12.8% w/w dry extract was obtained. Oral administration of C. jagus extract (1000 mg/kg) protected 50% of mice, while injection of a 30 min pre-incubated mixture of the same dose of extract and venom gave 100% protection against the lethal effects of E. ocellatus venom (10 mg/kg, i.m.). The intraperitoneal administration of the extract at 250 mg/kg, 30 min before the injection of E. ocellatus venom (10mg/kg, i.m.), significantly (p<0.05) prolonged the death time of poisoned mice. C. jagus extract (500 mg/kg, per os), gave 50% protection against B. arietans venom (9.5mg/kg, i.m.) in mice while the pre-incubation of a mixture of the same dose of venom and extract (500 mg/kg), prior to injection (i.p.) of the mixture, gave only 33.3% protection. The pre-incubation of 500 mg/kg of C. jagus extract with N. nigricollis venom (6 mg/kg) prior to i.p. injection of the mixture protected 50% of the treated mice. There were generally no significant differences in the death times of mice that were given the same dose of the extract orally 30 min before injection of the venoms and those administered with the pre-incubated mixtures of venom and extract. The pre-incubation of the extract and E. ocellatus venom (5mg/kg) for 30 min, before the i.m. injection of the mixture, significantly reduced infiltration of inflammatory cells to the site of injection 4h post treatment. The concentrations of plasma creatine kinase in poisoned mice were significantly (p<0.01 or p<0.05) reduced after the injection (i.p.) of C. jagus extract (1000 mg/kg) pre-incubated with E. ocellatus (5mg/kg) or B. arietans (7 mg/kg) venom, respectively. The bulb extract of C. jagus blocked the haemorrhagic activity of a standard haemorrhagic dose (2.8 mg/ml) of E. ocellatus venom at various concentrations (1.7, 3.3 and 6.7 mg/ml). The methanolic bulb extract of C. jagus was therefore able to significantly protect mice from death, myonecrosis and haemorrhage induced by the lethal effects of venoms of notable snake species in Nigeria.
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PMID:The anti-snake venom activities of the methanolic extract of the bulb of Crinum jagus (Amaryllidaceae). 1689 Feb 62

Stress is a major risk factor in drug addiction development and relapse. Virtually all drugs of abuse act by increasing extracellular dopamine levels in the striatum. To gain an understanding of the interaction between stress and drug exposure, we studied the effects of concomitant chronic nicotine and chronic stress exposure on mouse striatal dopamine levels. C57Bl6/J mice were treated with nicotine in the drinking water or control solution for at least 6 weeks. Some mice were chronically stressed by daily exposure to cold, shaking or restrain. Nicotine-treated mice showed up-regulation of epibatidine binding in several brain regions. In mice treated with both chronic nicotine and stress, epibatidine binding was increased in all studied areas except the dorsal striatum. Therefore, microdialysis was used to measure extracellular dopamine levels in the dorsal striatum of mice chronically treated with nicotine, stress, or both. To have a measure of striatal response to different challenges, we performed microdialysis after acute injection of saline, nicotine, and cocaine. Chronic nicotine enhanced nicotine-dependent dopamine release, while chronic stress blunted the response to cocaine. When mice were subjected to both chronic nicotine and chronic stress, nicotine- and cocaine-dependent dopamine release was undistinguishable from that of control animals. In conclusion, our data suggest that chronic stress and chronic nicotine counteract each other's effect on dopamine release in the striatum. This effect might be mediated by changes in nicotinic acetylcholine receptor up-regulation. This "normalization" of striatal function when both nicotine and stress are present might help explain the comorbidity between stress-related disorders and drug abuse.
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PMID:Opposing actions of chronic stress and chronic nicotine on striatal function in mice. 1853 90

The long-term behavior of the herbicide atrazine and its metabolites in the environment is of continued interest in terms of risk assessment and soil quality monitoring. Aqueous desorption, detection, and quantification of atrazine and its metabolites from an agriculturally used soil were performed 22 years after the last atrazine application. A lysimeter soil containing long-term aged atrazine for >20 years was subdivided into 10 and 5 cm layers (at the lysimeter bottom: soil 0-50 and 50-55 cm; fine gravel 55-60 cm depth, implemented for drainage purposes) to identify the qualitative and quantitative differences of aged (14)C-labeled atrazine residues depending on the soil profile and chemico-physical conditions of the individual soil layers. Deionized water was used for nonexhaustive cold water shaking extraction of the soil. With increasing soil depth, the amount of previously applied (14)C activity decreased significantly from 8.8% to 0.7% at 55-60 cm depth whereas the percentage of desorbed (14)C residues in each soil layer increased from 2% to 6% of the total (14)C activity in the sample. The only metabolite detectable by means of LC-MS/MS was 2-hydroxyatrazine while most of the residual (14)C activity was bound to the soil and was not desorbed. The amount of desorbed 2-hydroxyatrazine decreased with increasing soil depth from 21% to 10% of the total desorbed (14)C residue fraction. The amount of (14)C residues in the soil layers correlated well with the carbon content in the soil and in the aqueous soil extracts ( p value = 0.99 and 0.97, respectively), which may provide evidence of the binding behavior of the aged atrazine residues on soil carbon. The lowest coarse layer (55-60 cm) showed increased residual (14)C activity leading to the assumption that most (14)C residues were leached from the soil column over time.
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PMID:Spatial distribution and characterization of long-term aged 14C-labeled atrazine residues in soil. 1880 41

Dithioacetal derivatives with different para-substituents, XH, CH(3), OCH(3), Cl and NO(2) were synthesized and chemically immobilized on the surface of silica gel for the formation of five newly synthesized silica gel phases (I-V). Characterization of the silica gel surface modification by the organic compounds was accomplished by both the surface coverage determination as well as the infrared spectroscopic analysis. The metal sorption properties of the silica gel phases were studied to evaluate their performance toward metal-uptake, extraction and selective extraction processes of different metal ions from aqueous solutions based on examination of the various controlling factors. The studied and evaluated factors are the pH effect of metal ion solution on the metal capacity values (mmol g(-1)), equilibration shaking time on the percent extraction as well as the structure and substituent (X) effects on the determined mmol g(-1) values. The results of these studies revealed a general rule of excellent affinity of these silica gel phases-immobilized-dithioacetal derivatives for selective extraction of mercury(II) in presence of other interfering metal ions giving rise to a range of 94-100% extraction of the spiked mercury(II) in the metal ions mixture. The potential application of the newly synthesized silica gel phases (I-V) for selective extraction of mercury(II) from two different natural water samples, namely sea and drinking tap water, spiked with 1.0 and 10.0 ng ml(-1) mercury(II) were also studied by column technique followed by cold vapour atomic absorption analysis of the unretained mercury(II). The results indicated a good percent extraction and removal (90-100+/-3%) of the spiked mercury(II) by all the five silica gel phases. In addition, insignificant contribution by the matrix effect on the processes of selective solid phase extraction of mercury(II) from natural water samples was also evident.
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PMID:Silica gel-immobilized-dithioacetal derivatives as potential solid phase extractors for mercury(II). 1896 40

The ability to isolate high-yield pure and viable islets from human cadaver pancreas donors is dependent on donor factor as well as isolation factors. The aim of this study was to examine factors influencing islets recovery and in vivo function with an emphasis on donor and isolation methods as well as to compare the effectiveness of Liberase, widely used in clinical islet isolation, with Serva for the isolation of pure functional islets. The results of 123 islet isolations using Liberase for digestion were compared with those of 113 isolations with Serva. Islet equivalents per gram of tissue were similar between Liberase and Serva (3620 +/- 1858 vs. 4132 +/- 2104, p < 0.2) as well as the percent purity (75 +/- 16 vs. 74 +/- 15, p < 0.9). In vivo function of islets from 71 isolations (Liberase = 45, Serva = 26) were further tested by transplantation into NOD-SCID mice following short-term culture (< 6 days, n = 71). Our data show that both Liberase- and Serva-isolated islets showed similar function results following short-term culture. These data demonstrate that there is no difference in islet yield, purity, and function between the two enzymes. However, when these 71 isolations were analyzed for in vivo function with emphasis on donor factors, cold ischemia time (12.0 +/- 5.3 vs. 15.0 +/- 5.7, p < 0.04), islet integrity (1.6 +/- 0.7 vs. 1.3 +/- 0.5, p < 0.05), and female gender were the only factors that correlated with in vivo function. We also compared the mechanical-shaking method for islets isolation with hand-shaking methods. Our results show that although there is no different in islet yield, purity, and integrity between different enzymes using the same method, hand-shaking method yields more islets with better integrity than mechanical-shaking method.
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PMID:The effect of isolation methods and the use of different enzymes on islet yield and in vivo function. 1904 5

Icilin is a cold channel agonist that produces vigorous wet-dog shaking in rats. The shaking is accompanied by an increase in the level of extracellular glutamate in the brain. Hence, we hypothesized that icilin-induced wet-dog shakes are dependent on increased glutamatergic transmission and nitric oxide (NO) production. Rats injected with icilin (0.5, 1, 2.5, 5 mg/kg, i.p.) displayed a dose-related increase in wet-dog shakes. Pretreatment with LY 235959 (1, 2 mg/kg, i.p.), a NMDA receptor antagonist, or L-NAME (50 mg/kg, i.p.), a NO synthase (NOS) inhibitor, attenuated icilin-induced wet-dog shakes. The shaking was also reduced by intracerebroventricular L-NAME (1 mg/rat, i.c.v.) administration, indicating that the stimulant effect of icilin is dependent on central NO production. Pretreatment with 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) (10, 20 mg/kg, i.p.), an AMPA receptor antagonist, or ceftriaxone (200 mg/kg, i.p. for 5 days), a beta-lactam antibiotic and glutamate transporter subtype 1 (GLT-1) activator, did not alter the incidence of icilin-induced shaking. The present data reveal that icilin produces behavioral stimulation by a mechanism requiring NMDA receptor activation and nitric oxide production and suggest that glutamate and NO signaling play important roles in cold channel pharmacology.
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PMID:Icilin-induced wet-dog shakes in rats are dependent on NMDA receptor activation and nitric oxide production. 1924

Three detachment procedures (DP) were evaluated for their ability to remove particle-associated microbes from digesta in Rusitec fermenters fed a 30:70 alfalfa hay:concentrate diet. Forage and concentrate were incubated in separate nylon bags, and incubation residues were treated independently. Microbial biomass was labeled with (15)NH(4)Cl. Treatments were 1) MET: residues were incubated at 38 degrees C for 15 min with saline solution (0.9% NaCl) containing 0.1% methylcellulose with continuous shaking; 2) STO: residues were mixed with cold saline solution and homogenized with a stomacher for 5 min at 230 revolutions per min; and 3) FRE: residues were immediately frozen at -20 degrees C for 72 h, thawed at 4 degrees C, mixed with saline solution, and subjected to STO procedure. Common to all treatments was storing at 4 degrees C for 24 h after the treatment, homogenization, filtration, and resuspension of residues 2 times in the treatment solutions. Microbial pellets were obtained by centrifugation, and microbial removal was estimated indirectly by measuring removal of (15)N. The PCR-single-stranded conformation polymorphism analysis of the 16S ribosomal DNA was used to analyze the similarity between microbial communities attached to the substrate and those in the pellet obtained after each DP. There were no feed x DP interactions (P = 0.16 to 0.96) for any variable, except for N content in microbial pellets (P = 0.02). Detaching efficiency (P = 0.004) and total recovery (P = 0.01) were affected by DP, with STO showing the greatest values (mean values across substrates of 64.1% for detaching efficiency and 58.3% for total recovery) and MET the least values (57.0 and 51.8%). Similarity index between the microbes attached to substrates and those in the pellets were affected (P = 0.02) by DP, with MET showing greater (P < 0.02) values (84.0 and 86.4% for forage and concentrate, respectively) than FRE (72.5 and 67.8%) and STO having intermediate values (77.1 and 82.4%). There were no differences (P = 0.70) among particle-associated microbe pellets in their N content, but MET pellets had greater (P < 0.05) (15)N enrichments than those obtained by STO and FRE. Although STO was the most effective method to detach ruminal microbes from concentrate and forage, MET produced pellets with the greatest similarity to the microbial communities attached to the substrates and therefore could be considered the most appropriate DP method for treating digesta from Rusitec fermenters.
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PMID:Evaluation of procedures for detaching particle-associated microbes from forage and concentrate incubated in Rusitec fermenters: efficiency of recovery and representativeness of microbial isolates. 1925 33

Major depression is an illness with objective physical signs occurring with some consistency. These signs are retardation of movements and diminished gestures and expressions. The patient may appear tired, self-concerned, bored, and inattentive and display a loss of interest in the surroundings. Anxiety is a conspicuous and an integral element of affective state and may be expressed by severe restlessness and agitation. Muscle tension, wringing of hands, weeping and moaning, repeating over and over in a monotonous and stereotyped way phrases expressive of misery are all important clinical signs of major depression. Similarly tachycardia, dry tongue/mouth, sweaty palms and/or bodily extremities, cold clammy skin, pallor, pupillary dilatation, tremor, and the fluctuations in blood pressure with wide pulse pressure are all important and give away the underlying distress. These signs have formed an integral part of both the Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale as they have a positive correlation with the diagnosis and the severity of illness. Current practice of operational criteria does not help exclude patients with subjective perception of distress and also fails to make room for aetiopathogenesis. The DSM-IV does not include these physical signs as an integral part of the clinical picture of depression, consequently leaving the diagnosis of MDE to subjective criteria and perceptions. This could also explain a large placebo response in recent randomised controlled clinical trials.
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PMID:Major depression: an illness with objective physical signs. 1962 57

The aim of this study was to investigate patients with Hirayama disease in mainland China. A total of 192 patients (167 males, 25 females) collected from mainland China were included. Their clinical features, electrophysiology, imaging, muscle biopsy and laboratory tests, treatments, and prognosis were analysed. We compared the results with data from other countries or regions. The mean age at onset was 16.8 years. Onset was insidious, with symptoms of muscle weakness and atrophy in the distal muscles of the upper limb. Tremor on finger extension was noted in 77.6% of patients and cold paresis in 81.3%. The clinical course plateaued within five years in 89.1% of patients. Time from disease onset to definitive diagnosis of our series is longer than that from other countries or regions. There is no geographically based difference in the clinical presentation of Hirayama disease. Thus, our study supports the notion that Hirayama disease is a benign self-limited disorder with juvenile preponderance and asymmetric muscular atrophy of the distal portion of the upper limb. Hirayama disease is under-recognized in mainland China.
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PMID:Clinical features of Hirayama disease in mainland China. 1941 15


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