Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the effects of hyperthermia and facial fanning during hyperthermia on hand-grip exercise performance and thermoregulatory response, we studied eight male subjects, aged 20-53 years. Subjects exercised at 20% of maximal hand-grip strength in the sitting position under three conditions: normothermia (NT), hyperthermia without fanning (HT-nf) or with fanning at 5.5 m X sec-1 wind speed (HT-f). Hyperthermia (0.5 degrees C higher oesophageal temperature than in NT) was induced by leg immersion in water at 42 degrees C. Mean exercise performance was markedly reduced from 716 contractions (NT) to 310 (HT-nf) by hyperthermia (P less than 0.01) and significantly (P less than 0.05) improved to 431 (HT-f) by facial fanning. Hyperthermic exercise was accompanied by significant increases in forearm blood flow (71%) and the local sweat rate on the thigh (136%) at the end of exercise compared with that in NT. Heart rate (HR) and rating of perceived exertion (RPE) increased during exercise and were higher in HT-nf than in NT at any given time of exercise. Oesophageal, tympanic (Tty) and mean skin temperatures were also significantly higher in HT-nf than in NT. Facial fanning caused a marked decrease in forehead skin temperature (1.5-2.0 degrees C) and a slight decrease in Tty, HR and PRE compared with that in HT-nf at any given time of exercise. These results suggested that hyperthermia increased thermoregulatory demands and reduced exercise performance. Facial fanning caused decreases in face skin and brain temperatures, and improved performance.
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PMID:Effects of facial fanning on local exercise performance and thermoregulatory responses during hyperthermia. 383 Jan 41

The high selectivity of the phencyclidine derivative PRE-084 for sigma (sigma) sites is demonstrated. We previously reported that this compound is able to markedly attenuate the impairment of learning induced in mice by the non-competitive NMDA antagonist MK-801, and the cholinergic nicotinic antagonist mecamylamine. In this study, we examined the effect of PRE-084 on the impairment of learning induced by acute administration of the calcium channel antagonist nimodipine. Nimodipine (0.3 mg/kg i.p.) impaired the spontaneous alternation behaviour in a Y-maze, decreased the step-down latency (SDL) in a passive avoidance task, and altered place learning and retention in a water-maze paradigm, with no marked effect on the motility observed using an open-field test. Preadministration of PRE-084 resulted in an attenuation of the impairment of alternation, in the 0.3-1 mg/kg s.c. range, in a marked increase in SDL, at 1-3 mg/kg, and improved place learning and retention in the water-maze, at 1 mg/kg. The effects on alternation behaviour and passive avoidance were completely prevented by co-administration of the purported sigma antagonist BMY-14802 (10 mg/kg i.p.), implicating the sigma sites. These results confirm the beneficial effect of the sigma ligand PRE-084 on pharmacological models of learning impairments, and indicate that sigma sites may modulate Ca2+ fluxes through VDCC, which may in turn bear some as yet unknown relationship to the previously described interaction with neurotransmitter systems.
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PMID:Prevention of nimodipine-induced impairment of learning by the selective sigma ligand PRE-084. 878 20

The fluoride content of the enamel and dentine of premolars was used as a determinant of the availability of ingested fluoride in New Zealand prior to and following the introduction of water fluoridation 40 years ago. Premolar teeth, which developed during the periods (PRE and POST respectively) under study, were selected from teeth extracted from 12 to 14-year-old children resident in different geographic areas in the country. The fluoride content, determined by multiple proton microprobe analyses, of surface enamel, deep enamel, and dentine, were for PRE teeth 440, 65 and 115, respectively. For POST teeth the mean values were significantly (p<0.001) higher, by 69, 29 and 102% respectively. The relevance of the change in fluoride content was assessed by comparison with published reports on the fluoride content of teeth developed in communities exposed to low (<0.5 ppm), optimal (1-2 ppm) and high (>3 ppm) naturally occurring fluoride levels in drinking water. The PRE teeth had a fluoride content associated with a low fluoride exposure and POST teeth with optimal fluoride exposure during tooth development. It was concluded that fluoride availability in New Zealand teeth had increased over the past 30 years but this increase is compatible with exposure of the community to optimal rather than excessive levels of ingested fluoride.
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PMID:Fluoride content of the enamel and dentine of human premolars prior to and following the introduction of fluoridation in New Zealand. 886 31

A beneficial effect of sigma (sigma) agonists was previously described on several pharmacological models of learning impairments. We examined this effect in senescence-accelerated mice (SAM), which has been developed as a murine model of aging and cognitive dysfunction. SAMP8/Ta (P8, senescence-prone substrain), 10-12 months of age, showed significant impairments in mnemonic capacities, as compared to age-matched SAMR1/Ta controls (R1, senescence-resistant substrain). Tests included open-field behavior, spontaneous alternation performances in the Y-maze, step-down passive avoidance and place learning after repetitive training in a water-maze. Pretreatment with the sigma agonists JO-1784 (igmesine) or PRE-084, at 0.1-3 mg/kg, s.c., significantly improved spontaneous alternation and passive avoidance performances in P8. JO-1784 or PRE-084, at 1 mg/kg, also improved place learning in the water-maze, and retention, in term of escape latency. The implication of sigma sites was indicated by the lack of significant effect of JO-1783, the inactive enantiomer of JO-1784, and by the ability of BMY-14802 (5 mg/kg, i.p.) to antagonize the effects on passive avoidance of JO-1784 (0.5 mg/kg) or PRE-084 (1 mg/kg). Subchronic treatments with JO-1784 (0.5 mg/kg/day) or PRE-084 (1 mg/kg/day) during 10 days, allowed a significant improvement of learning during training in the water-maze, but retention was not significantly ameliorated. These results confirmed the interest of the SAM substrains as an experimental model for senile memory impairment and showed that sigma agonists could improve the quality of learning, although they seem less effective on long-term memory retrieval upon chronic administration.
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PMID:Beneficial effects of sigma agonists on the age-related learning impairment in the senescence-accelerated mouse (SAM). 889 5

The aim of the present study was to study salt and water metabolism in thyroid deficiency. We performed an oral water loading test (OWL) and a hypertonic 5% saline infusion test (HSI) in 16 patients with overt primary hypothyroidism before replacement treatment (PRE group) and after, in eight patients with subclinical hypothyroidism (SUB group) and in 16 normal individuals (CG group). In the PRE group, a lower free water clearance was detected in the OWL (P < 0.022), with lower plasma osmolality (OWL: P < 0.005; HSI: P < 0.001) and arginine vasopressin (AVP) (OWL: P < 0.001; HSI: P < 0.001) than the CG group, across both tests; they normalized with the replacement treatment. The same plasma abnormalities were detected in the SUB group with the HSI. Although the AVP and thirst thresholds did not differ between the groups, the lag between them was lower in the PRE (4.1+/-3.2 mOsm/kg) and SUB group (2.6+/-2.1 mOsm/kg) than in the CG group (13.3+/-9.2 mOsm/kg) (P < 0.05). There were no differences in atrial natriuretic hormone (ANH), plasma renin activity (PRA) and plasma aldosterone among the groups. These results indicate that plasma hypo-osmolality and low levels of AVP are present in primary hypothyroidism, and indeed are already present in the subclinical phase of the disease. An overlap between the thresholds of thirst and AVP seem to play a role in these abnormalities, but ANH, PRA and plasma aldosterone do not appear to contribute.
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PMID:Water metabolism disturbances at different stages of primary thyroid failure. 1124 Nov 75

Structural changes in Escherichia coli DNA photolyase induced by binding of a (cis,syn)-cyclobutane pyrimidine dimer (CPD) are studied by continuous-wave electron paramagnetic resonance and electron-nuclear double resonance spectroscopies, using the flavin adenine dinucleotide (FAD) cofactor in its neutral radical form as a naturally occurring electron spin probe. The electron paramagnetic resonance/electron-nuclear double resonance spectral changes are consistent with a large distance (> or =0.6 nm) between the CPD lesion and the 7,8-dimethyl isoalloxazine ring of FAD, as was predicted by recent model calculations on photolyase enzyme-substrate complexes. Small shifts of the isotropic proton hyperfine coupling constants within the FAD's isoalloxazine moiety can be understood in terms of the cofactor binding site becoming more nonpolar because of the displacement of water molecules upon CPD docking to the enzyme. Molecular orbital calculations of hyperfine couplings using density functional theory, in conjunction with an isodensity polarized continuum model, are presented to rationalize these shifts in terms of the changed polarity of the medium surrounding the FAD cofactor.
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PMID:Substrate binding to DNA photolyase studied by electron paramagnetic resonance spectroscopy. 1146 61

Sigma(1) (sigma(1)) receptor agonists showed anti-amnesic properties in pharmacological amnesia models. We now investigated whether the selective sigma(1) receptor agonist, 2-(4-morpholinoethyl)-1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084), could ameliorate spatial learning in aged animals, using a water-maze procedure. Wistar rats, 3 or 24 months old, were trained to locate a visible platform and then an invisible platform. Finally, a transfer test was performed during saline or PRE-084 treatment. Aged, but not adult, animals showed learning deficits unrelated to visual impairments. The PRE-084 treatment allowed aged animals to learn the new platform location, in terms of decreased latencies to the platform during training and increased presence in the quadrant during retention. The results of these experiments suggest a potential of selective sigma(1) receptor agonists as cognitive enhancers during ageing.
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PMID:Beneficial effect of the sigma(1) receptor agonist PRE-084 against the spatial learning deficits in aged rats. 1172 29

Paeoniae Radix (PR) is the root of traditional Chinese Herb named Paeonia lactiflora Pallas, which is commonly used to treat liver diseases in China for centuries. Several earlier studies have indicated that PR has anticancer growth activities, however the mechanism underlying these activities was unclear and remained to be elucidated. In this study, we evaluated the molecular mechanism of the effect of PR on human hepatoma cell lines, HepG2 and Hep3B. Our results showed that the water-extract of Paeoniae Radix (PRE) had inhibitory effect on the growth of both HepG2 and Hep3B cell lines. The induction of internucleosomal DNA fragmentation and chromatin condensation appearance, and accumulation of sub-G1 phase of cell cycle profile in PRE treated hepatoma cells evidenced that the cytotoxicity of PRE to the hepatoma cells is through activation of the cell death program, apoptosis. The activation of apoptosis by PRE is independent of the p53 pathway as Hep3B cell is p53-deficient. In addition, the differential gene expression of PRE treated HepG2 was examined by cDNA microarray technology and RT-PCR analysis. We found that the gene expression of BNIP3 was up-regulated while ZK1, RAD23B, and HSPD1 were down-regulated during early apoptosis of the hepatoma cell mediated by PRE. The elucidation of the drug targets of PR on inhibition of tumor cells growth should enable further development of PR for liver cancer therapy.
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PMID:Paeoniae Radix, a Chinese herbal extract, inhibit hepatoma cells growth by inducing apoptosis in a p53 independent pathway. 1221 74

The significance of ultraviolet-B radiation (UVBR: 280-315 nm)-induced DNA damage as a stress factor for Arctic marine macrophytes was examined in the Kongsfjord (Spitsbergen, 78 degrees 55.5'N, 11 degrees 56.0'E) in summer. UVBR penetration in the water column was monitored as accumulation of cyclobutane-pyrimidine dimers (CPD) in bare DNA. This showed that UVBR transparency of the fjord was variable, with 1% depths ranging between 4 and 8 m. In addition, induction and repair kinetics of CPD were studied in several subtidal macrophytes obtained from the Kongsfjord (5-15 m). Surface exposure experiments demonstrated CPD accumulation in Palmaria palmata, Devaleraea ramentacea, Phycodrys rubens, Coccotylus truncatus and Odonthalia dentata. In artificial light, field collected material of P. palmata, D. ramentacea, P. rubens and Laminaria saccharina showed efficient CPD repair, with only 10% of the artificially induced CPD remaining after 5 h. No significant differences in repair rate were observed among these species. CPD repair was slower or absent in O. dentata, C. truncatus and Monostroma arcticum, indicating that fast repair mechanisms such as photolyase were not continuously expressed in these species. CPD repair rates were not directly related to the vertical distribution of algae in the water column and to the reported UV sensitivity of the examined species. Dosimeter incubations showed that maximal exposure to DNA damaging wavelengths was low for all examined species. Furthermore, most species collected below the 1% depth for DNA damage displayed efficient CPD repair, suggesting that UVBR-induced CPD currently impose a minor threat for mature stages of these species growing in the Kongsfjord, Spitsbergen.
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PMID:Ultraviolet-B-induced cyclobutane-pyrimidine dimer formation and repair in Arctic marine macrophytes. 1246 43

The sigma(1) (sigma(1)) receptor represents a unique intracellular neuronal protein modulating several neurotransmitter responses with relevant effects on cognitive functions. We examined here its expression and behavioral efficacy during aging. The sigma(1) receptor expression was examined in young (2 months old) and aged (24 months old) C57BL/6 mouse brain using comparative RT-PCR and immunohistochemistry. The promnesic effect of PRE-084, a selective sigma(1) agonist, was assessed using a water-maze procedure. The sigma(1) mRNA expression was not affected during aging in the olfactory bulb, hippocampus, hypothalamus, cortex or cerebellum. The sigma(1) immunolabeling was intense in the olfactory bulb, hippocampus, hypothalamus and midbrain of the young mouse and the distribution appeared unchanged in the aged. The subcellular localization was similar in aged and younger animals, the protein being present on nuclear, mitochondrial, endoplasmic reticular and plasmic membranes. At the behavioral level, aged C57BL/6 mice showed deficits in the invisible platform learning, but not when the platform was visible. Animals subjected to a transfer test under repeated treatment with saline or PRE-084 significantly learned the new platform location. This study shows that sigma(1) receptor expression is preserved in aged animals and demonstrates the efficacy of a selective sigma(1) agonist against age-related memory deficits. Targeting this unique receptor may offer an original drug strategy during aging.
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PMID:Preserved sigma1 (sigma1) receptor expression and behavioral efficacy in the aged C57BL/6 mouse. 1292 69


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