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)

We studied 23 DMD and eight BMD patients using cardiac echo, 24 h ECG and positron emission tomography (PET) with the radiotracers N-13 ammonia and F-18 fluorine deoxyglucose. The ECG was abnormal in 23 cases with alterations in the PR and/or QT intervals, abnormal Q waves in the lateral leads and ST segment depression. Twenty-four hour ECG showed that patients were more likely to produce premature ventricular ectopic beats with advancing age and 17 patients had paroxysmal ST segment depression. LV function was normal or mildly reduced in 24 cardiac echoes. PET studies were visibly abnormal in 15 patients. Regional perfusion defects involving the apex, lateral or anterior left ventricular walls were present, nine cases demonstrated a corresponding increase in glucose metabolism. Three out of 15 demonstrated matched perfusion/metabolism defects. One BMD had severe LV dilation with globally poor perfusion and metabolism. The abnormalities seen with PET were confirmed with both quantitative and semi-quantitative analysis of radioactive counts. Similar results were obtained for both DMD and BMD, where both groups demonstrated significant regional perfusion/metabolism mismatches. We have shown a reduced uptake of N-13 ammonia which is indicative of a reduction in myocardial perfusion. The use of N-13 ammonia to measure perfusion has been validated in animal studies. PET with either N-13 ammonia- or oxygen labelled water can be used to measure myocardial perfusion. We chose N-13 ammonia as this was most readily available to us.
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PMID:Cardiac function, metabolism and perfusion in Duchenne and Becker muscular dystrophy. 888 52

Dental fluorosis or mottled enamel manifest itself as a brown, gray or black discolourations on the external enamel surfaces of the permanent teeth. The causative factor has been found to be the ingestion of fluorine in the drinking water more than 1 pp.m. In its most severe form the enamel discolouration provide a very displeasing appearance. Many times friends and relatives tease the patient that these stains are associated with smoking and/or poor oral hygiene. Such unwarranted, lose and inflicting personal remarks leads an individual into a severe psychological depression. A clinical study was under taken with its aims and objectives to evaluate the efficaciousness of 18% hydrochloric acid with pumice and McInnes solution with pumice in fighting the various forms of fluorosis stains and also observe and record their actions and reactions with the patients and the vitalities of the treated teeth.
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PMID:Clinical evaluation of two different techniques for the removal of fluorosis stains. 949 71

Chronic fatigue syndrome (CFS) has been widely studied by neuroimaging techniques in recent years with conflicting results. In particular, using single-photon emission computed tomography (SPECT) and perfusion tracers, hypoperfusion has been found in several brain regions, although the findings vary across research centers. The objective of this study was to investigate brain metabolism of patients affected by CFS, using [18F]fluorine-deoxyglucose (18FDG) positron emission tomography (PET). We performed 18FDG PET in 18 patients who fulfilled the criteria of the working case definition of CFS. Twelve of the 18 patients were females; the mean age was 34 +/- 15 years (range, 15-68) and the median time from CFS diagnosis was 16 months (range, 9-138). Psychiatric diseases and anxiety/neurosis were excluded in all CFS patients. CFS patients were compared with a group of 6 patients affected by depression (according to DSM IV-R) and 6 age-matched healthy controls. The CFS patients were not taking any medication at the time of PET, and depressed patients were drug-free for at least 1 week before the PET examination. The PET images examined 22 cortical and subcortical areas. CFS patients showed a significant hypometabolism in right mediofrontal cortex (P = 0.010) and brainstem (P = 0.013) in comparison with the healthy controls. Moreover, comparing patients affected by CFS and depression, the latter group showed a significant and severe hypometabolism of the medial and upper frontal regions bilaterally (P = 0.037-0.001), whereas the metabolism of brain stem was normal. Brain 18FDG PET showed specific metabolism abnormalities in patients with CFS in comparison with both healthy controls and depressed patients. The most relevant result of our study is the brain stem hypometabolism which, as reported in a perfusion SPECT study, seems to be a marker for the in vivo diagnosis of CFS.
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PMID:Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data. 979 Apr 83

This study was undertaken to clarify the role of high-energy phosphate metabolism in hydrogen peroxide-induced cardiac dysfunction using phosphorus and fluorine nuclear magnetic resonance spectroscopy. The exposure of a Langendorff-perfused heart to hydrogen peroxide (200-400 micromol/L, 8 min) provoked biphasic contractile dysfunction characterized by a transient depression of left ventricular developed pressure during the administration of hydrogen peroxide and a delayed elevation of left ventricular end-diastolic pressure after the washout of hydrogen peroxide. The initial phase of cardiac dysfunction correlated well with the accumulation of sugar phosphates (r = 0.89, p < 0.01). Furthermore, we demonstrated that glibenclamide, a potent inhibitor of the ATP-sensitive K+ channel, attenuated the initial depression of developed pressure. On the other hand, the delayed elevation of end-diastolic pressure correlated well with the total ATP depletion (r = 0.96, p < 0.01). However, ATP loss was supposed to be a mere result from the increased ATP consumption corresponding to a rise in intracellular free Ca2+ (from the control value of 315+/-23 nmol/L to 708+/-104 after the administration of hydrogen peroxide, p < 0.01), which also paralleled the elevation of end-diastolic pressure. Thus glycolytic inhibition and intracellular Ca2+ overload are independently responsible for the biphasic contractile dysfunction induced by hydrogen peroxide.
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PMID:Role of high-energy phosphate metabolism in hydrogen peroxide-induced cardiac dysfunction. 1071 30

This investigation of fluvoxamine and fluoxetine-norfluoxetine distributions in vivo at steady-state and of quantitative kinetics in brain and plasma after drug therapy interruption was performed by fluorine nuclear magnetic resonance spectroscopy (19F MRS), spectroscopic imaging (MRSI), and plasma HPLC on 12 subjects treated for depression. MRSI suggests a homogeneous distribution of 19F MRS visible fluvoxamine mainly in brain. Fluvoxamine steady-state brain concentrations (12 +/- 5 microM; n = 13) and brain-to-plasma concentration ratios (10 +/- 2; n = 12) were similar to those of combined fluoxetine-norfluoxetine (CF-norfluoxetine) (13 +/- 6 microM; n = 4 and 10 +/- 6; n = 4). Fluvoxamine brain elimination half-life (79 +/- 24 hours; n = 4) was significantly shorter than that of CF-norfluoxetine (382 +/- 48 hours; n = 2). Fluvoxamine brain-to-plasma-half-life-ratio was 2.2 +/- 0.3 (n = 4), contrarily to CF-norfluoxetine (1.0 +/- 0.3; n = 2). This study shows that quantitative pharmacokinetics in target organs by 19F MRS in vivo should prove useful for understanding and investigating outcome of treatment modifications and side effects.
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PMID:Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine by fluorine magnetic resonance spectroscopy. 1098 70

The 5-HT1A subtype of receptors for the neurotransmitter serotonin is predominantly located in the limbic forebrain and is involved in the modulation of emotion and the function of the hypothalamus. Since 5-HT1A receptors are implicated in the pathogenesis of anxiety, depression, hallucinogenic behaviour, motion sickness and eating disorders, they are an important target for drug therapy. Here, we review the radioligands which are available for visualisation and quantification of this important neuroreceptor in the human brain, using positron emission tomography (PET) or single-photon emission tomography (SPET). More than 20 compounds have been labelled with carbon-11 (half-life 20 min), fluorine-18 (half-life 109.8 min) or iodine-123 (half-life 13.2 h): structural analogues of the agonist, 8-OH-DPAT, structural analogues of the antagonist, WAY 100635, and apomorphines. The most successful radioligands thus far are [carbonyl-11C] WAY-100635 (WAY), [carbonyl-11C]desmethyl-WAY-100635 (DWAY), p-[18F]MPPF and [11C]robalzotan (NAD-299). The high-affinity ligands WAY and DWAY produce excellent images of 5-HT1A receptor distribution in the brain (even the raphe nuclei are visualised), but they cannot be distributed to remote facilities and they probably cannot be used to measure changes in endogenous serotonin. Binding of the moderate-affinity ligands MPPF and NAD-299 may be more sensitive to serotonin competition and MPPF can be distributed to PET centres within a flying distance of a few hours. Future research should be directed towards: (a) improvement of the metabolic stability in primates; (b) development of a fluorinated radioligand which can be produced in large quantities and (c) production of a radioiodinated or technetium-labelled ligand for SPET.
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PMID:Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system. 1120 45

Fluorine magnetic resonance spectroscopy ((19)F MRS) measurements of fluoxetine and metabolite concentration in the human brain underestimate true drug levels because of a bound, MRS-"invisible" pool of drug molecules. Magnetization transfer (MT) spectroscopy may be a useful technique for characterizing this bound pool of fluoxetine in the brain. Six subjects on consistent daily doses of fluoxetine underwent (19)F MT spectroscopy on a 1.5-T scanner using a train of three preparation pulses at -3000 Hz off resonance with 0.5 W of peak power deposition in tissue. One subject was scanned at multiple time points after initiation of drug therapy. Magnetization transfer signal contrast was quantified using VARPRO-based time domain fitting software. Magnetization transfer signal contrast was quantifiable with mean MT signal depression of 12.5% (SD = 5.0, n = 6). An inverse relationship between brain concentration and the MT signal contrast of fluoxetine was found (r = -.82, Spearman coefficient =.007). This study is the first in vivo application of (19)F MT spectroscopy and the first to demonstrate a quantifiable MT effect for a psychotropic medication in the human brain. Findings suggest that fluoxetine is substantially bound in the brain and that individual differences, inversely related to brain concentration, can be detected in the magnitude of MT contrast.
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PMID:Magnetization transfer of fluoxetine in the human brain using fluorine magnetic resonance spectroscopy. 1133 Oct 88

Hypothyroidism is often associated with defective memory, psychomotor slowing, and depression. However, the relationship between thyroid status and cognitive or psychiatric disturbances remains unclear. Using psychometric scales, 10 patients who had undergone total thyroidectomy for thyroid carcinoma were evaluated for depression, anxiety, and psychomotor slowing; they were examined both when euthyroid and hypothyroid after thyroid hormone withdrawal. Positron emission tomography was used, with oxygen-15-labeled water and fluorine-18F-labeled 2-deoxy-2fluoro-D-glucose as the tracers, to correlate the regional cerebral blood flow and cerebral glucose metabolism with the mental state in patients. Two different image analysis techniques (regions of interest and statistical parametric maps) were applied. In hypothyroidism, there was a generalized decrease in regional cerebral blood flow (23.4%, P < 0.001) and in cerebral glucose metabolism (12.1%, P < 0.001) and there were no specific local defects. Patients were also significantly more depressed (P < 0.001), anxious (P < 0.001) and psychomotor slowed (P < 0.005) in hypo than in euthyroid status. These results indicate that the brain activity was globally reduced in severe hypothyroidism of short duration without the regional modifications usually observed in primary depression.
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PMID:Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study. 1150 25

Considerable efforts have been engaged in the design, synthesis and pharmacological characterization of radioligands for imaging the serotonin transporter, based on its implication in several neuropsychiatric diseases, such as depression, anxiety and schizophrenia. In the 5-halo-6-nitroquipazine series, the fluoro derivative has been designed for positron emission tomography (PET). The corresponding 5-iodo-, 5-bromo- and 5-chloro N-Boc-protected quipazines as labelling precursors, as well as 5-fluoro-6-nitroquipazine as a reference compound have been synthesized. 5-[(18)F]Fluoro-6-nitroquipazine has been radiolabelled with fluorine-18 (positron-emitting isotope, 109.8 min half-life) by nucleophilic aromatic substitution from the corresponding N-Boc protected 5-bromo- and 5-chloro-precursors using K[(18)F]F-K(222) complex in DMSO by conventional heating (145 degrees C, 2 min) or microwave activation (50 W, 30-45 s), followed by removal of the protective group with TFA. Typically, 15-25 mCi (5.5-9.2 GBq) of 5-[(18)F]fluoro-6-nitroquipazine (1-2 Ci/micromol or 37-72 GBq/micromol) could be obtained in 70-80 min starting from a 550-650 mCi (20.3-24.0 GBq) aliquot of a cyclotron [(18)F]F(-) production batch (2.7-3.8% non decay-corrected yield based on the starting [(18)F]fluoride). Ex vivo studies (biodistribution in rat), as well as PET imaging (in monkey) demonstrated that 5-[(18)F]fluoro-6-nitroquipazine ([(18)F]-1d) readily crossed the blood brain barrier and accumulated in the regions rich in 5-HT transporter (frontal- and posterial cortex, striata). However, the low accumulation of the tracer in the thalamus (rat and monkey) as well as the comparable displacement of the tracer observed with both citalopram, a -HT re-uptake inhibitor and maprotiline, a norepinephrine re-uptake inhibitor (rat), indicate that 5-[(18)F]fluoro-6-nitroquipazine ([(18)F]-1d) does not have the suggested potential for PET imaging of the serotin transporter (SERT).
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PMID:Synthesis of a fluorine-18-labelled derivative of 6-nitroquipazine, as a radioligand for the in vivo serotonin transporter imaging with PET. 1205 50

Corticosteroids regulate a variety of essential physiological functions, such as mineral balance and stress. The great interest in these steroids, especially the glucocorticoids, stems from roles they are thought to play in neuropsychiatric disorders, such as severe depression and anxiety.The development of glucocorticoid receptor (GR) ligands which are appropriately labeled with short-lived positron-emitting radioisotopes would allow the non-invasive in-vivo imaging and mapping of brain GRs by means of positron emission tomography (PET). In this context we have synthesized a series of novel arylpyrazolo steroids exhibiting different substitution patterns at the D-ring of the steroid skeleton, as ligands for brain GRs. Special attention was given to 4-fluorophenyl pyrazolo steroids, which are known to display high binding affinity toward the GR. The compounds were evaluated in a competitive radiometric receptor binding assay to determine their relative binding affinities (RBA) to the GR. Some compounds show good binding affinities of up to 56% in comparison to dexamethasone (100%). In initial experiments, selected candidates were labeled with the positron emitter fluorine-18 and in one case with the gamma-emitter iodine-131.
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PMID:Synthesis of novel arylpyrazolo corticosteroids as potential ligands for imaging brain glucocorticoid receptors. 1260 9


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