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)

In response to cues signifying the approach of winter, adult Artemia franciscana produce encysted embryos that enter diapause. We show that respiration rates of diapause embryos collected from the field (Great Salt Lake, Utah) are reduced up to 92% compared with postdiapause embryos when measured under conditions of normoxia and full hydration. However, mitochondria isolated from diapause embryos exhibit rates of state 3 and state 4 respiration on pyruvate that are equivalent to those from postdiapause embryos with active metabolism; a reduction in these rates (15%-27%) is measured with succinate for two of three collection years. Respiratory control ratios for diapause mitochondria are comparable to or higher than those from postdiapause embryos. The P : O flux ratios are statistically identical. Our calculations suggest that respiration of intact, postdiapause embryos is operating close to the state 3 oxygen fluxes measured for isolated mitochondria. Cytochrome c oxidase (COX) activity is 53% lower in diapause mitochondria during one collection year; the minimal impact of this COX reduction on mitochondrial respiration appears to be due to the 31% excess COX capacity in A. franciscana mitochondria. Transmission electron micrographs of embryos reveal mitochondria that are well differentiated and structurally similar in both states. As inferred from the similar amounts of mitochondrial protein extractable, tissue contents of mitochondria in diapause and postdiapause embryos are equivalent. Thus, metabolic depression during diapause cannot be fully explained by altered properties of isolated mitochondria. Rather, mechanisms for active inhibition or substrate limitation of mitochondrial metabolism in vivo may be operative.
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PMID:Differences in isolated mitochondria are insufficient to account for respiratory depression during diapause in artemia franciscana embryos. 1528 11

In animal models frakefamide (FF) is a potent analgesic that acts as a peripheral active mu-selective receptor agonist. In this double-blind, randomized, double dummy four-way crossover study in 12 healthy male subjects, we investigated the effects on resting ventilation of FF and 2 dose levels of morphine compared with placebo. Each drug was infused for 6 h. The subjects received 1.22 mg/kg FF, 0.43 mg/kg morphine (M-large), and 0.11 mg/kg morphine (M-small). Sodium chloride 9 mg/mL was used as placebo. Ventilation was measured by pneumotachography and inline capnography. Blood was collected and plasma concentrations of FF and morphine and its metabolites were analyzed. Within 15 min after administration of FF all subjects complained of a transient myalgia, which disappeared within 30 min. At target measurement (335 min), there were no differences in tidal volume among the groups. Respiratory rates were, however, slower in the two M-groups (P < 0.05 in M-small and P < 0.001 in M-large) compared with FF and placebo. Minute volume was significantly less in the M-large group compared with the FF (P < 0.01) and placebo (P < 0.01) groups. This difference was reflected by an elevated ETco(2) in the M-large group (P < 0.01). We conclude that, during resting ventilation, FF, unlike morphine, did not cause central respiratory depression. This suggests that FF has only peripheral mu-opioid agonist activity in humans.
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PMID:A novel molecule (frakefamide) with peripheral opioid properties: the effects on resting ventilation compared with morphine and placebo. 1572 57

Sodium chloride (NaCl) is widely used as a deicing agent on roadways. There are numerous anecdotal reports of poisoning of passerine birds by road salt in the United States and Canada, but little is known about the toxicity of NaCl to songbirds. The objectives of this study were to determine the lethal dose range for NaCl in a representative passerine species (house sparrow [Passer domesticus]); to determine the clinical, physiologic, and pathologic effects of sublethal and lethal oral NaCl exposure; and to assess the potential for recovery after exposure to granular salt or highly concentrated salt solutions. The up-and-down method was used in a pilot study to estimate the lethal oral dose of granular NaCl in wild caught house sparrows. The toxicity of highly concentrated NaCl solution also was investigated. This was followed by an acute dose response study in which house sparrows were dosed orally with granular NaCl at 0, 500, 1,500, 2,500, or 3,500 mg/kg. Sparrows were deprived of water for 6 hr postexposure (PE) in an attempt to mimic specific winter conditions. Groups of three birds at each dose were euthanized at 1, 3, 6, and 12 hr PE, and samples were collected for histopathology and brain and plasma electrolyte analyses. Results indicated an approximate mean lethal dose (LD50) of 3,000-3,500 mg/kg in water-deprived birds, which is similar to mammalian values. House sparrows dosed with a concentrated solution of NaCl generally died at doses of 8,000 mg/kg. Clinical signs observed at >or=1,500 mg/kg included rapid onset (<30 min) of depression (indicated by reduced activity and reduced response to visual and auditory stimuli), ataxia, inability to fly or perch, and death in as little as 45 min. Birds that survived for 6 hr usually recovered. Plasma Na concentrations >200 mmol/l were consistently associated with clinical signs. Pathologic lesions consisted of edema and distension of the caudoventral thin muscled region of the gizzard and were observed 1 hr PE in most birds dosed with >or=500 mg/kg. Brain Na concentrations in clinically ill sparrows and those that died of NaCl toxicity ranged from 1,297 to 1,615 (mean=1,450; SD=115) ppm wet weight or 5,603 to 6,958 (mean=6,367; SD=454) ppm dry weight, which differed significantly from control birds. No histologic lesions were observed in brain sections of exposed birds, likely reflecting the acute nature of the exposure. However, fluid accumulation beneath the koilin layer of the gizzard was observed in the majority of birds at high dosage levels. These results indicate that passerines ingesting relatively small numbers of road salt granules or small quantities of highly concentrated NaCl solutions are at risk of sodium poisoning.
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PMID:Toxicity of sodium chloride to house sparrows (Passer domesticus). 1610 71

Methanol remains to be a major public and environmental health hazard. Formic acid is the toxic metabolite responsible for the metabolic acidosis observed in methanol poisoning in humans, in non-human primates and in folate-depleted rodents. Cytochrome oxidase inhibition by formate leads to lactic acid accumulation, which contributes significantly to metabolic acidosis. Toxic effects in human beings are characterized by formic acidemia, metabolic acidosis, ocular toxicity, nervous system depression, blindness, coma and death. Elimination of formate is one of the principles of management in methanol poisoning. Hemodialysis facility is not readily available in all the places, in developing countries like India. Formate dehydrogenase (EC 1.2.1.2) acts directly over formate and converts formate into CO(2) in the presence of NAD. Effect of single intravenous bolus infusion of formate dehydrogenase, obtained from Candida boidinii; in methanol-intoxicated folate deficient rat model was evaluated. Folate depletion induced by methotrexate (MTX) treatment. Carbicarb (Carb) (equimolar solution of sodium carbonate and sodium bicarbonate) was used to treat metabolic acidosis. Experimental design consists of seven groups, namely Saline control, methanol control, MTX control, Enzyme control, MTX-methanol control, MTX-methanol-Carb and MTX-methanol-Carb-Enz group. Male wistar rats treated with MTX (0.3mg/kg) for a week, were injected (i.p.) with methanol (4 gm/kg), 12h latter, Carbicarb solution was infused, following this enzyme was infused (i.v.) in bolus. Blood samples were collected every 15 min for an hour from the cannulated left jugular vein and blood methanol, formate were estimated, respectively, with HPLC and fluorimetric assay. Blood pH, blood gases pO(2), pCO(2) and bicarbonate were monitored with blood gas analyzer in order to evaluate acid base status of the animal. Results obtained show that there is significant elimination of formate within 15 min. It may be concluded that single bolus infusion of formate dehydrogenase facilitates fast removal of formate, a highly toxic metabolite in methanol poisoning.
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PMID:Therapeutic response to single intravenous bolus administration of formate dehydrogenase in methanol-intoxicated rats. 1618 30

Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo-pituitary-adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1beta (1 microg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2-4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1beta injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1beta also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1beta-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1beta-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1.
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PMID:Relationships among the behavioral, noradrenergic, and pituitary-adrenal responses to interleukin-1 and the effects of indomethacin. 1633 Jan 80

Frakefamide (FF), is a new peripherally acting mu-opioid receptor agonist. The aim of this double-blind, randomized, double-dummy, four-way, crossover study was to investigate FF effects on hypercarbic and hypoxic ventilation at steady-state after a 6-h infusion. We compared the effect with 2 clinical doses of morphine (M-small and M-large) and placebo in 12 healthy men. The subjects received 1.22 mg/kg of FF, 0.44 mg/kg of M-large, and 0.11 mg/kg of M-small. Sodium chloride 9 mg/mL was used as placebo. Ventilation was studied by pneumotachography and in-line capnography. There were no ventilatory effects caused by FF or placebo. As expected, large doses of morphine influenced both hypercarbic and hypoxic ventilatory responses. We conclude that there were no signs of central respiratory depression caused by FF after 6 h of constant infusion, which supports a peripheral action of the compound. However, morphine caused a dose-dependent central depression during the hypercarbic ventilatory response and a mild depression of hypoxic ventilatory response.
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PMID:A novel molecule with peripheral opioid properties: the effects on hypercarbic and hypoxic ventilation at steady-state compared with morphine and placebo. 1636 13

The present study evaluated the cardioprotective potential of bosentan, a mixed endothelin type A and B receptor antagonist, in the myocardial ischaemia-reperfusion model of myocardial infarction. Adult male wistar rats (175-225 g) were divided into three groups: sham operated, non-myocardial ischaemia-reperfusion (SHAM); saline-treated myocardial ischaemia-reperfusion control (CON); bosentan-treated myocardial ischaemia-reperfusion (BOS). All animals were anaesthetized and subjected to 40 min. occlusion of left anterior descending coronary artery followed by 120 min. of reperfusion. Saline or drug was administered to the CON or BOS group, respectively, 20 min. after the left anterior descending coronary artery occlusion. Haemodynamic parameters viz. systolic arterial pressure, diastolic arterial pressure and heart rate were recorded throughout the experimental period. Hearts were subsequently excised and processed for histopathological and infarct size evaluation and for biochemical estimation of cardiac specific enzyme creatine kinase-MB (CK-MB) and myocardial malondialdehyde, a lipid peroxidation marker. Myocardial ischaemic reperfusion resulted in severe myocardial injury, depression of haemodynamic function, significant increase in malondialdehyde levels and decline in CK-MB isoenzyme activity in the heart tissue. Administration of bosentan (3 mg/kg, intravenously) slightly improved haemodynamic effects, decreased myocardial oxygen consumption, significantly (P<0.01) attenuated the rise in malondialdehyde levels and loss of myocardial CK-MB isoenzyme activity compared to the CON group, whereas bosentan administration significantly reduced the percentage area of fiber loss and infarct area. It is therefore concluded that endothelin-1 may mediate myocardial damage produced by ischaemia and reperfusion and that dual blockade of endothelinA and endothelinB receptors may have potential as a mode of therapy for myocardial infarction.
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PMID:Cardioprotective effects of bosentan, a mixed endothelin type A and B receptor antagonist, during myocardial ischaemia and reperfusion in rats. 1670 Aug 25

Urmia Lake has been designated as an international park by the United Nations. The lake occupies a 5700 km2 depression in northwestern Iran. Thirteen permanent rivers flow into the lake. Water level in the lake has been decreased 3.5 m in the last decade due to a shortage of precipitation and progressively dry climate. Geologically the lake basin is considered to be a graben of tectonic origin. Na, K, Ca, Li and Mg are the main cations with Cl, SO4, and HCO3 as the main anions. F & Br are the other main elements in the lake. A causeway crossing the lake is under construction, which may affect the lake's annual geochemistry. The main object of this project is mainly to consider the potential of K-mineral production along with ongoing salt production. Seven hundred and four samples were taken and partially analyzed for the main cations and anions. Surface water (0.5 m. depth) was analyzed for Na, K, Mg, Ca, Br and Li, and averaged 87.118 g/lit, 1.48 g/lit, 4.82 g/lit, 4.54 g/lit, 1.19 ppm and 12.7 ppm respectively for the western half of the lake. Sodium ranged between 84 to 91.2 g/lit, and showed higher concentrations in the south than in the north. This unexpected result may be caused by shallower depth in the south and a higher net evaporation effect. Calcium ranged between 4.2 to 5 g/lit, apparently slightly higher in the north. K is higher in the south, possibly due to rivers entering from south that may carry slightly higher K in solution. In the middle-range samples (0.5-5 m.), K averaged 1.43 g/lit and ranged from 1.40 to 1.46 g/lit. At this intermediate depth the distribution of K is clearly higher to the south of the causeway that is currently under construction. It is not clear whether this increase is the effect of the causeway or the effect of the salty Aji-Chay River to the east, and the Khoy salt domes to the north of the lake. At depth (5 m-10 m), K averaged 1.48 g/lit and ranged from 1.4 to 1.49 g/lit, differing only in the second decimal from the average of the middle and surface samples. Ignoring the small difference between the averages of the three sample depths, the distribution of K is highly homogeneous in the lake water due to the mixing process. Therefore causeway construction has not yet strongly affected K distribution, or it may be at the starting point. Magnesium concentration ranged from 4.6 to 5-g/lit, and was elevated in the south. This differs somewhat compared to calcium. Lithium, with an average of 12-13 ppm, is slightly higher in the south, and has not shown any significant variation in all three seasons. Iodine was below the detection limit in the lake. Urmia Lake, geochemically, is highly uniform both to the south and north of the causeway, in both the surface and deep brines. K and Mg, which average 1.48 and 6.6 g/lit in order, could be elements worth production in addition to the NaCl currently being produced from the lake. Br, F, Li and B in the limit of <50 ppm don't look to be in the economical range.
Saline Syst 2006 Jul 11
PMID:Hydrogeochemistry of seasonal variation of Urmia Salt Lake, Iran. 1683 70

Hypernatraemia induced by chronic injections of sodium chloride provokes thermal depression in the agamid lizard, Ctenophorus (formerly Amphibolurus) ornatus, with a fall of two degrees Celsius in the mean body temperature selected behaviourally in a photo-thermal gradient. The placement of an electrolytic lesion in the base of the hypothalamus, designed to eliminate secretion of the neuropeptide arginine vasotocin (AVT), did not affect the lizards' thermoregulatory behaviour and their Preferred Body Temperature (PBT) was not significantly different from that of unoperated controls. Saline loading, however, did not induce thermal depression in these tract-operated individuals and their PBT was significantly higher than that of salt-loaded intact individuals. When AVT was injected into operated, salt-loaded, animals, however, thermal depression was observed, supporting the hypothesis that thermal depression brought about by hypernatraemia is mediated through the action of AVT. AVT similarly significantly depressed the PBT of injected intact individuals by 3.2 degrees C when compared with hydrated controls. Immunostaining for AVT confirmed that the lesions placed in the region of the median eminence virtually eliminated AVT located in the neurohypophysial tract, and the pars nervosa. This is the first report of an effect of this peptide on behavioural thermoregulation in a lizard.
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PMID:Effect of hypernatraemia and the neurohypophysial peptide, arginine vasotocin (AVT) on behavioural thermoregulation in the agamid lizard, Ctenophorus ornatus. 1690 23

Antidepressants may be effective treatment for smoking cessation and new evidence on relationship between smoking and depression is emerging. Extracts of the plant Hypericum perforatum possess antidepressant activity in humans and reduce nicotine withdrawal signs in mice. Both nicotine and H. perforatum administration elicit changes in serotonin (5-HT) formation in the brain. On this basis, we investigated the possible involvement of 5-HT in the beneficial effects of H. perforatum on nicotine withdrawal signs. With the aim to induce nicotine dependence, nicotine (2 mg/kg, four intraperitoneal injections daily) was administered for 14 days to mice (NM). Saline (controls, M) or H. perforatum extract (Ph 50, 500 mg/kg) were orally administered immediately after the last nicotine injection for 30 days after nicotine withdrawal. Another group of animals treated with nicotine (14 days) and successively with H. perforatum extract was intraperitoneally co-administered with selective 5-HT receptorial antagonist WAY 100635 (WAY) (1 mg/kg). All animals were evaluated for locomotor activity and abstinence signs, 24 after nicotine withdrawal. Brain 5-HT metabolism was evaluated in the cortex of mice sacrificed 30 days after nicotine withdrawal through evaluation of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/5-HT ratio. After nicotine withdrawal measurement of 5-HT metabolism in the cortex showed a reduction of 5-HT content while animals treated only with Hypericum extract showed a significant reduction of total abstinence score compared to controls. WAY inhibited the reduction of total abstinence score induced by H. perforatum. Moreover, 5-HT1A expression has been evaluated 30 days after nicotine withdrawal. Our results, show a significant increase of cortical 5-HT content in NM treated with H. perforatum, with a concomitant significant increase of 5-HT1A receptor. So, it is possible to suggest an involvement of 5-HT in beneficial effects of H. perforatum on suffering produced by nicotine withdrawal in dependent mice.
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PMID:Serotonin mediates beneficial effects of Hypericum perforatum on nicotine withdrawal signs. 1768 33


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