UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of forskolin on 5-hydroxytryptamine (5-HT)-induced inositol phosphate (IP) and Ca2+ mobilisation was investigated in canine cultured aorta smooth muscle cells (ASMCs). Pretreatment of ASMCs with forskolin attenuated 5-HT-induced IP accumulation and Ca2+ mobilisation in a time- and concentration-dependent manner. The half-maximal effects (pEC50) of forskolin to attenuate IP and Ca2+ responses to 5-HT occurred at concentrations of 6.28 and 6.64, respectively. Pretreatment of ASMCs with cholera toxin caused a similar inhibition on 5-HT-induced responses. Even after treatment with forskolin for 24 h, the 5-HT-induced responses were still inhibited. The inhibitory effect of forskolin resulted from both a depression of the maximal response and a shift to the right of the concentration-effect curves of 5-HT in these responses. The water-soluble forskolin analogue L-858051 [7-deacetyl-7beta-(gamma-N-methylpiperazino)-butyryl forskolin] significantly inhibited the 5-HT-stimulated IP accumulation. In contrast, the addition of 1,9-dideoxy forskolin, an inactive forskolin analogue, had little effect on IP response. Moreover, SQ-22536 [9-(tetrahydro-2-furanyl)-9-H-purin-6-amine], an inhibitor of adenylate cyclase, and both H-89 [N-(2-aminoethyl)-5-iosquinolinesulphonamide] and HA-1004 [N-(2-guanidinoethyl)-5-iosquinolinesulphonamide], inhibitors of cAMP-dependent protein kinase (PKA), attenuated the ability of forskolin to inhibit the 5-HT-stimulated accumulation of IP in ASMCs. These results indicate that activation of cAMP/PKA might inhibit the 5-HT-stimulated IP accumulation and consequently reduce Ca2+ mobilisation, or inhibit both responses independently.
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PMID:Forskolin inhibits 5-hydroxytryptamine-induced phosphoinositide hydrolysis and Ca+2 Mobilisation in canine cultured aorta smooth muscle cells. 1053 Aug 79

In adult male Sprague-Dawley rats anesthetized with pentobarbital sodium, we elucidated the molecular consequence of central alpha(2)-adrenoceptor activation. The hypotensive and negative chronotropic and inotropic actions of the alpha(2)-adrenoceptor agonist guanabenz were used as our experimental index. Intracerebroventricular administration of pertussis toxin (2.5 &mgr;g) significantly attenuated the cardiovascular suppressant effects of the aminoguanidine compound (100 &mgr;g/kg i.v.). However, application of N-ethylmaleimide (0.125 or 0.250 &mgr;g), phorbol 12-myristate 13-acetate (1.25 or 2.50 &mgr;g), cholera toxin (1.25 or 2.50 &mgr;g) or forskolin (12.5 or 25.0 &mgr;g) into the lateral cerebral ventricle elicited no appreciable blunting effect on the circulatory depression produced by guanabenz. These results were essentially duplicated when pertussis toxin (0.125 or 0.250 &mgr;g), N-ethylmaleimide (0.0125 or 0.05 &mgr;g), phorbol 12-myristate 13-acetate (0.125 or 0.25 &mgr;g), cholera toxin (0.125 or 0.25 &mgr;g) or forskolin (1.25 or 2.50 &mgr;g) was microinjected bilaterally to the nucleus reticularis gigantocellularis, a medullary site believed to be intimately related to the antihypertensive action of guanabenz. These findings suggest that stimulation of the alpha(2)-adrenoceptors in the medulla oblongata may result in the activation of a pertussis toxin-sensitive GTP-binding regulatory protein. They further suggest that the biologic signals subsequent to this action may not be linked to Gs, Gi or Gp but possibly Go. Copyright 1994 S. Karger AG, Basel
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PMID:Further Elucidation of a Pertussis Toxin-Sensitive Transmembrane Signaling Mechanism Involved in Central alpha(2)-Adrenoceptor Activation in the Rat. 1172 2

Refinement of the retinal pathways to the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN) is mediated by nitric oxide (NO). Long-term depression (LTD) can also be induced in SC and LGN during the time at which these pathways are refined, and this LTD is partially dependent on NO and L-type Ca(2+) channel function. In an effort to determine whether NO-mediated pathway refinement is also mediated by Ca(2+) channel function, we have examined the refinement of the retinocollicular and retinogeniculate pathways in mice which lack the gene for the Ca(2+) channel beta(3) subunit (CCKO) and which have significantly reduced L-type Ca(2+) currents. Injections of the anterograde tracer cholera toxin subunit B/HRP were made into one eye of these knockout animals and in wild-type mice ages postnatal day (P) 13, P19, and P26. After 48 hours, mice were perfused and sections processed by using tetramethylbenzidine histochemistry. Labeling distribution in some animals was analyzed quantitatively. Obvious differences in the distribution of the ipsilateral retinocollicular pathway were observed at P15, with the pathway being more exuberant in CCKO mice. This difference was statistically significant. More subtle differences were seen at P21 and P28. Obvious differences were also seen in the contralateral retinogeniculate pathway which in CCKO mice filled most of the domain normally occupied by ipsilateral eye fibers. This difference was also statistically significant. We conclude that reduction in L-type Ca(2+) currents has an effect on axonal refinement similar to that which occurs in NO knockout mice, which supports the possibility that L-type Ca(2+) channel-dependent LTD mediates NO-dependent axonal refinement.
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PMID:Development of the visual pathway is disrupted in mice with a targeted disruption of the calcium channel beta(3)-subunit gene. 1174 16

Most health professionals in developing and developed countries consider oral rehydration therapy (ORT) to be the most effective treatment for diarrhea. An estimated 1,500 million episodes of diarrhea occur annually and 3 million of these results in death of children 5 years old. Caretakers must give increased amounts of fluids (rice water, tea, and gruel) to children with diarrhea to prevent dehydration. If they become dehydrated, caretakers must take them to a health workers so he/she can assess and treat them with oral rehydration solution (ORS) or, in the case of severe dehydration, rehydrate them intravenously. Drugs should not be used to treat diarrhea cases. Nevertheless, surveys in 4 Asian nations indicated that drug use ranged from 22-68% of diarrhea episodes and ORS use ranged only from 9-21%. Drug use is very expensive. In fact, Peru spent US$2 million on antidiarrheals in 1988- 1989. Further, drugs often make up 40% of health care costs in developing countries, so ORS use reduces these costs. Indeed drug us deflects from correct case management of diarrhea. In addition, drugs have no proven value for acute diarrhea. They do not decrease the fluid loss responsible for death and may even have serious side effects, such as central nerve depression and gastrointestinal toxicity. If health workers suspect cholera or dysentery, however, they can administer effective and relatively inexpensive antibiotics. Since the early 1980s, almost all developing countries had a national control of diarrheal disease program. In several countries, hospital admission rates for diarrhea fell 61% and the case fatality rate fell 71% after ORT introduction. Some hospitals have even saved as much as 60% in costs due to these declines. WHO has a book available which covers rational use of drugs in managing acute diarrhea in children.
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PMID:Rational management of diarrhoea in children. 1228 31

The mammalian dorsal raphe nucleus (DRN) is composed of sub-divisions with different anatomical and functional properties. Using cholera toxin subunit B as a retrograde tracer, DRN subdivisions projecting to the lateral geniculate nucleus and to the primary visual cortex were examined in the Mongolian gerbil. DRN neurons projecting to the lateral geniculate nucleus were observed in the lateral DRN (rostrally) and in the ventromedial DRN (caudally), while DRN cells projecting to the primary visual cortex were observed at all rostral-caudal levels in the ventromedial DRN. These results demonstrate a significant overlap between the DRN projections to the lateral geniculate and superior colliculus, and show that only the caudal ventromedial DRN projects to all three major visual targets: the lateral geniculate nucleus, primary visual cortex, and superior colliculus. Since the DRN is involved in depression and other neuropsychiatric disorders, as well as is affected by many psychotropic substances, these data may help to develop new treatments and therapies targeting specific DRN subdivisions.
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PMID:Subdivisions of the dorsal raphe nucleus projecting to the lateral geniculate nucleus and primary visual cortex in the Mongolian gerbil. 1263 3

We have previously reported that dopamine (DA) depresses non-NMDA receptor-mediated glutamatergic transmission in the rat parabrachial nucleus (PBN), an interface between brainstem and forebrain that is implicated in autonomic regulation. This work examined cellular signalling pathways that might underlie this DA-induced synaptic depression. Direct activation of adenylyl cyclase with 10 microM forskolin increased the evoked EPSC but did not occlude DA-induced EPSC depression. Similarly, a preferential protein kinase A inhibitor, H-7 (10 microM), did not block DA's synaptic effects. Incubation of slices with cholera toxin (CTX; 1 microgram/ml) or pertussis toxin (PTX; 0.5 microgram/ml) for 20 h, procedures used to irreversibly activate or disable the G(s) and G(i) proteins, respectively, did not change DA's effects. The putative phospholipase C inhibitor, U-73122 (10 microM) and its inactive analogue U-73343 (10 microM) did not alter DA-induced reduction in the EPSCs. Alterations in signalling molecules downstream of phospholipase C including depleting internal calcium stores by thapsigargin and cyclopiazonic acid and blocking protein kinase C with chelerythrine, had no effect on DA-induced synaptic depression. Furthermore, DA's depression of the non-NMDA response was not blocked by APV, an NMDA receptor antagonist. Finally, DA depressed evoked, pharmacologically isolated NMDA receptor-mediated synaptic responses while increasing NMDA-induced inward currents in the PBN. These results indicate that DA-induced synaptic effects in the PBN are not through the activation of cholera or pertussis toxin sensitive G proteins. Furthermore, it does not employ the adenylyl cyclase-cAMP-PKA cascade, the phospholipase C signalling pathway and NMDA receptor-coupled mechanisms to depress excitatory synaptic transmission in the PBN.
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PMID:Dopamine-induced synaptic depression in the parabrachial nucleus is independent of CTX- and PTX-sensitive G-proteins, PKA and PLC signalling pathways. 1467 13

Abstract Activation of potassium (K(+)) currents plays a critical role in the control of programmed cell death. Because pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to inhibit the apoptotic cascade in the cerebellar cortex during development, we have investigated the effect of PACAP on K(+) currents in cultured cerebellar granule cells using the patch-clamp technique in the whole-cell configuration. Two types of outward K(+) currents, a transient K(+) current (I(A)) and a delayed rectifier K(+) current (I(K)) were characterized using two different voltage protocols and specific inhibitors of K(+) channels. Application of PACAP induced a reversible reduction of the I(K) amplitude, but did not affect I(A), while the PACAP-related peptide vasoactive intestinal polypeptide had no effect on either types of K(+) currents. Repeated applications of PACAP induced gradual attenuation of the electrophysiological response. In the presence of guanosine 5'-[gammathio]triphosphate (GTPgammaS), PACAP provoked a marked and irreversible I(K) depression, whereas cell dialysis with guanosine 5'-[betathio]diphosphate GDPbetaS totally abolished the effect of PACAP. Pre-treatment of the cells with pertussis toxin did not modify the effect of PACAP on I(K). In contrast, cholera toxin suppressed the PACAP-induced inhibition of I(K). Exposure of granule cells to dibutyryl cyclic adenosine monophosphate (dbcAMP) mimicked the inhibitory effect of PACAP on I(K). Addition of the specific protein kinase A inhibitor H89 in the patch pipette solution prevented the reduction of I(K) induced by both PACAP and dbcAMP. PACAP provoked a sustained increase of the resting membrane potential in cerebellar granule cells cultured either in high or low KCl-containing medium, and this long-term depolarizing effect of PACAP was mimicked by the I(K) specific blocker tetraethylammonium chloride (TEA). In addition, pre-incubation of granule cells with TEA suppressed the effect of PACAP on resting membrane potential. TEA mimicked the neuroprotective effect of PACAP against ethanol-induced apoptotic cell death, and the increase of caspase-3 activity observed after exposure of granule cells to ethanol was also significantly inhibited by TEA. Taken together, the present results demonstrate that, in rat cerebellar granule cells, PACAP reduces the delayed outward rectifier K(+) current by activating a type 1 PACAP (PAC1) receptor coupled to the adenylyl cyclase/protein kinase A pathway through a cholera toxin-sensitive Gs protein. Our data also show that PACAP and TEA induce long-term depolarization of the resting membrane potential, promote cell survival and inhibit caspase-3 activity, suggesting that PACAP-evoked inhibition of I(K) contributes to the anti-apoptotic effect of the peptide on cerebellar granule cells.
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PMID:PACAP inhibits delayed rectifier potassium current via a cAMP/PKA transduction pathway: evidence for the involvement of I k in the anti-apoptotic action of PACAP. 1506 41

Epidemiology in the past was concerned essentially by the study of infectious diseases which were the cause of huge mortalities especially since urbanisation was initiated. Epidemics of pest, typhus, cholera, influenza a.o. were common. The epidemics were halted by better hygiene, vaccination and antibiotics. Since the second world war epidemiology was dominated by an "epidemic" of new chronic diseases, especially heart disease and cancer. This was due to an increase in life span and to an increase in smoking habits and in the intake of saturated fat and a too small intake of fruit and vegetables combined with a too high intake of salt (NaCl). Gradually epidemiology evolved as the study of the causes, the distribution, the risk factors and the prevention of chronic diseases, but also including accidents, suicide, depression a.o., diseases with a mass occurrence at the population level. The importance of nutrition as a determinant of health gradually became recognized, but remains undervalued by the medical profession. Mortality at the population level follows some simple mathematical laws and can be represented accurately (r2>0.99) between the ages of 35 and 84 year by either Gompertz equations (ln mortality versus age) or by a polynomial equation (ln mortality versus age, age2). This is valid for all populations and both sexes and remains valid at times of great and rapid changes in mortality. This shows that measures for prevention should be directed towards the total population. The future of epidemiology should be directed towards the slowing of the ageing process at the population level by a healthy life style consisting of: not smoking, avoiding obesity, a fair amount of physical activity and a healthy nutrition i.e little salt, little saturated fat, an adequate amount of omega-3 fatty acids and a large amount of fruit and vegetables, with an occasional glass of red wine. This contains the secret of a long and healthy life. Conceptually it will be important to determine whether a maximum human life span, genetically determined, exists. A maximal rectangularization of the mortality curve should then be the ultimate goal. At the same time the possible re-emergence of old and new infectious diseases (SARS, Ebola, BSE, AIDS) should be kept in mind.
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PMID:Epidemiology: past, present and future. 1564 67

Classical swine fever virus (CSFV), an enveloped positive-stranded RNA virus in the genus Pestivirus of the Flaviviridae family, is the causative agent of a highly contagious swine disease characterized by symptoms of hemorrhagic fever and immune depression, usually leading to substantial economic losses. The serological methods for detection of CSFV antibody such as ELISA are important means for the diagnosis of CSFV and immune surveillance. It is difficult to obtain CSFV antigen with high quality using traditional method because its titration titer is low in cell culture. CSFV has four structural protein named C, E0, El and E2. The E2 protein contains major antigenic determinants that are conserved between different CSFV strains and involved in neutralization by antibodies. So recombinant E2 protein can be developed as an alternative to the intact viral antigen. So far, CSFV E2 have not been expressed in E. coli with high level. Many factors, such as the secondary structure, the stability of 5' and 3' terminus of gene, the location of SD sequence and the bias of codes, are involved in the expressing level of foreign gene in E. coli . In this study, two sites of the E2 gene sequence were confirmed to be detrimental to its expression efficiency in E. coli through the computer-aided analysis. So they were mutated using recombinant PCR without changing the amino acids sequence of CSFV E2 gene. A plasmid was constructed by inserting the mutated E2 gene into the prokaryotic expression vector pET-28a(+) and named pETE2. The E. coli competent host BL21 (DE3)lysS transformed with pETE2 could express the E2 gene at high level, amounting to 28% of the total protein of the induced recombinant bacteria at the presence of IPTG. Except the hydrophobic transmembrane domain at C terminus, the recombinant E2 protein includes the total aa sequence. So it contains all the potential linear antigen epitopes of E2 protein because hydrophobic aa region can not form epitope. The recombinant E2 protein was CSFV-specific as proved by Western blotting and indirect ELISA. The rabbits immunized with the recombinant E2 can be protect from the challenge of hog cholera lapinized virus. This is the first report that E2 gene is expressed with high level expression in E. coli. In conclusion, it is an effective measure that mutate the CSFV E2 gene to increase its expression level in E. coli. The recombinant CSFV E2 protein possess fine immunonicity and can be used the antigen for the detection of CSFV antibody.
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PMID:[Site-directed mutagensis of the major antigen E2 gene of CSFV, its high level expression in Escherichia coli and the immunonicity of recombinant E2 protein]. 1596 61

In individuals with a narrow or collapsible upper airway, sleep-related hypotonia of upper airway muscles leads to recurrent airway obstructions. Brainstem noradrenergic neurons reduce their activity during slow-wave sleep and become silent during rapid eye movement sleep; this may cause state-dependent changes in the motor output and reflexes. The loss of noradrenergic excitation is a major cause of sleep-related depression of activity in upper airway muscles innervated by the hypoglossal nerve. Our goal was to identify and compare the pontomedullary sources of catecholaminergic (CA) projections to the hypoglossal motor nucleus (Mo12) and the adjacent viscerosensory nucleus of the solitary tract (NTS). In 10 Sprague-Dawley rats, retrograde tracers, Fluoro-Gold or B sub-unit of cholera toxin, were microinjected (5-20nl) into the Mo12, NTS, or both nuclei. Tyrosine hydroxylase (TH) was used as a marker for CA neurons. Following tracer injections into the Mo12, retrogradely labeled and TH-positive neurons were found in the A1/C1 (18.5%), A5 (43.5%), A7 (15.0%), and sub-coeruleus (21.0%) regions, and locus coeruleus (1.7%). In contrast, following injections into the NTS, these proportions were: 48.0, 46.5, 0.2, 0.9, and 4.3%, respectively. The projections to both nuclei were bilateral, with a 3:2 ipsilateral predominance. In four animals with one tracer injected into the Mo12 and the other in NTS, TH-positive cells containing both tracers were found only in the A5 region. Thus, the pontomedullary sources of CA projections to the Mo12 and NTS differ, with only A1/C1 and A5 groups having significant projections to these two functionally distinct targets.
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PMID:Differential pontomedullary catecholaminergic projections to hypoglossal motor nucleus and viscerosensory nucleus of the solitary tract. 1713 70

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