Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repeated administration of interferon-alpha (IFN-alpha) or pegylated IFN-alpha to patients with chronic hepatitis C viral infection induces a flu-like syndrome as well as neuropsychiatric side effects, which are well recognized, but poorly understood. Although pegylation appears to have improved viral response rates in patients with hepatitis C, there are still neurotoxicities associated with pegylated IFN-alpha therapy, in particular, depression, which can compromise and sometime prevent successful completion of antiviral treatment. This study assessed the effects of two forms of pegylated IFN-alpha [peginterferon-alfa-2a (PEG-2a) and peginterferon-alfa-2b (PEG-2b)] in rats in order to develop an animal model of IFN-induced "depression" (often described as sickness behavior) that can be used to more comprehensively investigate the neurochemical mechanisms of IFN-induced depression. Sixty male and female Lewis rats were randomly assigned to one of six treatment groups: (1) saline (SAL)+SAL (2) SAL+PEG-2a; (3) SAL+PEG-2b; (4) selective serotonin reuptake inhibitor (SSRI)+SAL, (5) SSRI+PEG-2a; (6) SSRI+PEG-2b. Rats were pretreated with intraperitoneal (i.p.) saline (0.9%) or 7.5mg/kg/day fluoxetine for 1 week, followed by 3 weeks of concurrent i.p. administration of 650 microg/wk of PEG-2a or PEG-2b. Using locomotor activity, the forced swim test, and weight gain as behavioral measures of sickness behavior, our data showed that Lewis rats did not develop an IFN-induced "depressive syndrome." Western blot analyses of brain and liver tissue indicated that signal transducer and activator of transcripton (STAT1) was not phosphorylated following IFN-alpha administration, suggesting that the pegylated compounds may not have bound type I IFN receptors in the rat. Collectively, our data suggest that Lewis rats are likely not a useful model to study IFN-induced depression.
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PMID:Administration of pegylated interferon-alpha-2a or -2b does not induce sickness behavior in Lewis rats. 1704 81

In this paper, a simple and green modification method is developed for biomolecules analysis on poly(dimethylsiloxane) (PDMS) microchip with successful depression of nonspecific biomolecules adsorption. O-[(N-succinimdyl)succiny]-o'-methyl-poly(ethylene glycol) was explored to form hydrophilic surface via in-situ grafting onto pre-coated chitosan (Chit) from aqueous solution in the PDMS microchannel. The polysaccharide chains backbone of Chit was strongly attracted onto the surface of PDMS via hydrophobic interaction combined with hydrogen bonding in an alkaline medium. The methyl-poly(ethylene glycol) (mPEG) could produce hydrophilic domains on the mPEG/aqueous interface, which generated brush-like coating in this way and revealed perfect resistance to nonspecific adsorption of biomolecules. This strategy could greatly improve separation efficiency and reproducibility of biomolecules. Amino acids and proteins could be efficiently separated and successfully detected on the coated microchip coupled with end-channel amperometric detection at a copper electrode. In addition, it offered an effective means for preparing biocompatible and hydrophilic surface on microfluidic devices, which may have potential use in the biological analysis.
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PMID:In-situ grafting hydrophilic polymer on chitosan modified poly(dimethylsiloxane) microchip for separation of biomolecules. 1732 Aug 88

The objective of this study was to evaluate data retrospectively on accidental ingestion of ethylene glycol (EG), based on calls to the Czech Toxicological Information Centre and from toxicological laboratories, in the years 2000-2004. All patients who ingested a known amount of EG and/or subjects with measured serum EG levels were included. A variety of clinical and laboratory parameters was collected. The medical records of 86 subjects, who had ingested from one to three swallows of EG, were analysed. The following findings emerged-metabolic acidosis (41%), vomiting (36%), nephrotoxicity (10%), and CNS depression (9%). In 15 children, the time interval between ingestion and hospitalisation was 1 hour or less. Ethanol was given to 12 children (four as first aid), and none developed hypoglycaemia. Of the 71 adults, 93% were treated with ethanol (19 as first aid). No side effects were documented. Seventeen patients received haemodialysis (HD). Two patients recovered without HD; their EG levels were higher than in the HD-treated patients. Unintentional EG ingestion usually involves ingestion of a small amount of EG, and was connected with mild signs of intoxication. Early therapy with ethanol alone appears sufficient in such cases, and represents no risk of adverse effects.
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PMID:Does unintentional ingestion of ethylene glycol represent a serious risk? 1733 80

Bupropion, an atypical antidepressant commonly used for depression and smoking cessation, is well known to cause seizures in both therapeutic use and overdose, but cardiac effects have been reported as minimal, usually sinus tachycardia. We describe an ingestion of bupropion estimated to be greater than 2 g by a 3-year-old boy that resulted in seizures. The child was decontaminated with whole bowel irrigation (WBI), and he experienced aspiration of polyethylene glycol and electrolyte solution used for the WBI. The patient ultimately developed hypotension and bradycardia requiring cardiopulmonary resuscitation due to the effects of the bupropion combined with the complications of WBI. In contrast to previous literature, which showed few clinical effects aside from seizures from ingestion of bupropion by children, our case highlights the dangers of pediatric bupropion ingestion and highlights risks of WBI.
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PMID:Cardiotoxicity associated with accidental bupropion ingestion in a child. 1800 23

2-Butoxyethanol (BE) is a one member of a family of ethylene glycol monoalkyl ethers that are used in a variety of industrial and household products. The clinical features of human and animal BE intoxications mainly include metabolic acidosis, CNS depression and coma, hemolytic anemia, hematuria, and renal injury. It is believed that metabolic activation of BE to butoxyacetic acid (BAA) is responsible for these pathologic changes. The treatment of BE poisoning have been based on an inhibition of the metabolic pathway enzymes which convert BE to toxic metabolites. Therefore, a comparison was made between antidotal properties of pyrazole (PY) and 4-methylpyrazole (MP) in rats subcutaneously intoxicated with BE. It was found that both antidotes effectively protected animals against appearance of hemolytic anemia signs induced by BE. MP appears to be more efficient than PY. These data confirm the beneficial role of alcohol dehydrogenase (ADH) inhibitors in BE intoxication.
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PMID:Pyrazole and methylpyrazole for the treatment of 2-butoxyethanol poisoning. 1766 57

We determined the homogeneous nucleation temperature depression, DeltaT(f,hom), the equilibrium melting point depression, DeltaT(m), and the value lambda, which can be obtained from the linear relationship DeltaT(f,hom)=lambdaDeltaT(m), for aqueous solutions of PEG (200-20,000 g mol(-1)), PVP (10,000, 35,000, 40,000 g mol(-1)), and dextran (10,000 g mol(-1)) in the concentration range 0-40 wt% using the emulsion method. The molecular weight dependence of T(f,hom), T(m), and lambda in PEG aqueous solutions was found to change in the vicinity of Mw 600-1540 at all concentrations. In addition, it was confirmed that for all of the polymers studied, there was a good linear relationship between lambda and the logarithmic value of the self-diffusion coefficient D(0) of the solute molecule. These results indicate that the parameters that describe non-equilibrium freezing, such as T(f,hom) and lambda, are dependent on solution properties such as viscosity and self-diffusion of solute molecules.
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PMID:Ice nucleation and supercooling behavior of polymer aqueous solutions. 1816 69

Hepatitis C (HCV)-related end stage liver disease is a primary cause of morbidity and mortality in people with HIV. Despite this, co-infected patients have low rates of HCV treatment initiation and completion. This is in large part due to the risk of pegylated-interferon alpha (PEG-IFN-alpha)-related neuropsychiatric complications. We describe the design of a multicentre randomized, placebo-controlled trial that evaluates whether antidepressant prophylaxis is superior to early detection and treatment of depression in increasing the successful completion of HCV therapy. Seventy-six HIV+ adults with chronic HCV infection requiring therapy and with no contraindications to PEG-IFN-alpha/ribavirin will be randomized in a 1:1 ratio to receive citalopram or placebo starting three weeks prior to HCV treatment. A novel aspect of the trial design is the built-in management of emergent depression while maintaining the blinded treatment assignment. This will permit the comparison of prophylactic versus therapeutic use of citalopram. The primary outcome is the average proportion of prescribed PEG-IFN-alpha and ribavirin doses taken per month at weeks 12 and 24, and will be compared between treatment arms. The study will also compare the development of moderate-to-severe depression between treatment arms. A unique feature of this trial will be the use of Telepsychiatry to standardize observer-administered neuropsychiatric evaluations. Assessments of anxiety, quality of life, and adherence to therapy, as well as pathogenetic studies of neuropsychiatric side effects, will be conducted. Intention-to-treat analyses using random regression modeling will be employed to analyze longitudinal data on prescribed PEG-IFN-alpha and ribavirin doses. Survival analyses will be used to compare the time to the development of depression between the two arms. Effective prevention of a broad range of neuropsychiatric symptoms by citalopram has the potential to diminish PEG-IFN-alpha associated morbidity and consequently, allow a greater number of patients to complete full therapy.
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PMID:CTN-194 (PICCO): design of a trial of citalopram for the prevention of depression and its consequences in HIV-hepatitis C co-infected individuals initiating pegylated interferon/ribavirin therapy. 1826 53

The knowledge of the solubility of PEG 1500 as well as the swelling and melting point variation in supercritical CO(2) in a relatively high-pressure range is a necessary prerequisite to set-up pharmaceutical processes dealing with the polymer in the molten state. Experiments carried out in a pressurized view cell indicated that the PEG 1500 progressively decreases its melting point and increases its volume as a consequence of the absorption of the CO(2). The melting point depression was pronounced (from 46 to 28 degrees C) up to 8.7 MPa. Thereafter a constant value was attained. Analogously, under CO(2) the polymer increased its volume (about 34%) until 10 MPa; after this pressure, the polymer volume no longer increased. PEG 1500 showed solubility in SC-CO(2) at 35 and 55 degrees C in the 10-40 MPa range in the order of 10(-6)mole fraction. An empirical model based on solubility parameters was used to fit the experimental data and to predict the maximum concentration achievable by the polymer in the dense gas, as well as to quantify the polymer concentration at low pressures where the experimental determination may be extremely difficult.
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PMID:Swelling, melting point reduction and solubility of PEG 1500 in supercritical CO2. 1829 90

Curcumin, a yellow pigment present in the Indian spice turmeric (associated with curry powder), has been linked with suppression of inflammation; angiogenesis; tumorigenesis; diabetes; diseases of the cardiovascular, pulmonary, and neurological systems, of skin, and of liver; loss of bone and muscle; depression; chronic fatigue; and neuropathic pain. The utility of curcumin is limited by its color, lack of water solubility, and relatively low in vivo bioavailability. Because of the multiple therapeutic activities attributed to curcumin, however, there is an intense search for a "super curcumin" without these problems. Multiple approaches are being sought to overcome these limitations. These include discovery of natural curcumin analogues from turmeric; discovery of natural curcumin analogues made by Mother Nature; synthesis of "man-made" curcumin analogues; reformulation of curcumin with various oils and with inhibitors of metabolism (e.g., piperine); development of liposomal and nanoparticle formulations of curcumin; conjugation of curcumin prodrugs; and linking curcumin with polyethylene glycol. Curcumin is a homodimer of feruloylmethane containing a methoxy group and a hydroxyl group, a heptadiene with two Michael acceptors, and an alpha,beta-diketone. Structural homologues involving modification of all these groups are being considered. This review focuses on the status of all these approaches in generating a "super curcumin.".
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PMID:Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. 1877 80

Three alcoholics (62 years, 47 years, 83 years) died between 11 and 18 h after ingestion of ethylene glycol (EG). One person committed suicide. Observed symptoms of intoxication were seizures, respiratory depression, arrhythmias and hypotonia. All died in hospital after failed attempts at resuscitation, one person did so after an 11h dialysis treatment. EG was detected in blood in concentrations of between 1 and 3mg/L (toxic range: >0.3mg/L). One case presented a blood alcohol concentration (bac) of 1.14 per thousand. Further toxic substances were not found. Using special staining techniques, oxalate crystals were found in samples from the kidneys, explaining renal failure, and in the medial layer of cerebral vessels.
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PMID:Oxalate-crystals in different tissues following intoxication with ethylene glycol: three case reports. 1925 53


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