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)

Mice were injected for 30 days with plasma from three patients with Lambert-Eaton Myasthenic Syndrome (LEMS). Recordings were made from the perineurial sheath of motor axon terminals of triangularis sterni muscle preparations. The objective was to characterize pharmacologically the identity of kinetically distinct, defined potential changes associated with motor nerve terminal Ca2+ currents (ICa) that were affected by LEMS autoantibodies. ICa elicited at 0.01 Hz were significantly reduced in amplitude by approximately 35% of control in LEMS-treated nerve terminals. During 10-Hz stimulation, ICa amplitude was unchanged in LEMS-treated motor nerve terminals, but was depressed in control. During 20- or 100-Hz trains, facilitation of ICa occurred in LEMS-treated nerve terminals whereas in control, no facilitation occurred during the trains at 20 Hz and marked depression occurred at 100 Hz. Saturation for amplitude and duration of ICa in control terminals occurred at 2 and 4-6 mM extracellular Ca2+, respectively; in LEMS-treated terminals, the extracellular Ca2+ concentration had to increase by two to three times of control to cause saturation. Amplitude of the two components of ICa observed when the preparation was exposed to 50 microM 3,4-diaminopyridine and 1 mM tetraethylammonium were both reduced by LEMS plasma treatment. The fast component (ICa,s) was reduced by 35%, whereas the slow component (ICa, s) was reduced by 37%. omega-Agatoxin IVA (omega-Aga-IVA; 0.15 microM) and omega-conotoxin-MVIIC (omega-CTx-MVIIC; 5 microM) completely blocked ICa in control motor nerve terminals. The same concentrations of toxins were 20-30% less effective in blocking ICa in LEMS-treated terminals. The residual ICa remaining after treatment with omega-Aga-IVA or omega-CTx-MVIIC was blocked by 10 microM nifedipine and 10 microM Cd2+. Thus LEMS plasma appears to downregulate omega-Aga-IVA-sensitive (P-type) and/or omega-CTx-MVIIC-sensitive (Q-type) Ca2+ channels in murine motor nerve terminals, whereas dihydropyridine (DHP)-sensitive (L-type) Ca2+ channels are unmasked in these terminals. Acute exposure (90 min) of rat forebrain synaptosomes to LEMS immunoglobulins (Igs; 4 mg/ml) did not alter the binding of [3H]-nitrendipine or [125I]-omega-conotoxin-GVIA (-omega-CgTx GVIA) when compared with synaptosomes incubated with an equivalent concentration of control Igs. Conversely, LEMS Igs significantly decreased the Bmax for [3H]-verapamil to approximately 45% of control. The apparent affinity of verapamil (KD) for the remaining receptors was not significantly altered. Thus acute exposure of isolated central nerve terminals to LEMS Igs does not increase DHP sensitivity, whereas it reduces the number of binding sites for verapamil but not for nitrendipine or omega-CgTx-GVIA. These results suggest that chronic but not acute exposure to LEMS Igs either upregulates or unmasks DHP-sensitive Ca2+ channels in motor nerve endings.
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PMID:Passive transfer of Lambert-Eaton myasthenic syndrome induces dihydropyridine sensitivity of ICa in mouse motor nerve terminals. 974 21

Much evidence points to a significant involvement of the classical neurotransmitters 5-HT and DA in affective disorders with possible changes in different structures of the CNS and also at different levels of the signal transduction chain, i.e., receptor, synthesis, uptake or release. We have used chronic isolated housing as an animal model of depression. These isolated rats enabled the study of KCl-induced release of 5-HT and DA from nucleus accumbens, prefrontal cortex and hippocampal slices. The following questions were addressed: first, if there is a change in the depolarization dependent release of DA and 5-HT from these CNS structures, and second, if the release is through the classical exocytotic mechanism. A significant increase in KCl stimulated release of 5-HT was observed in chronically isolated animals when compared to controls. 5-HT release was completely abolished from controls or isolated animals, when slices were incubated with Krebs containing zero Ca2+/10 mM Mg2+, the inorganic Ca2+ channel blockers, Cd2+ or Ni2+ and the calmodulin inhibitor, trifluoperazine. The organic Ca2+ channel blockers nifedipine and D-600 were less effective in inhibiting the stimulated 5-HT release. KCl stimulated DA release was only significantly increased from hippocampus slices, of isolated, but not control animals. This release was also highly Ca2+-dependent. The basal release of DA and 5-HT was similar in control and isolated animals and was not affected by the Ca2+ channel antagonists. The results suggest that extracellular Ca2+-dependent release of 5-HT and, to a lesser degree, of DA, is increased in this chronic animal model of depression in several CNS structures.
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PMID:Ca2+ dependency of serotonin and dopamine release from CNS slices of chronically isolated rats. 978 82

The actions of external Cd2+ on the twitch and tetanic contractions, action potentials and potassium (K+) contractures of rat soleus muscle fibre bundles have been investigated. Cd2+ at 1-1.5 mM did not significantly alter tetanic tension, but increased twitch tension and increased the duration and overshoot of action potentials. At >/=3 mM, Cd2+ (1) depressed tetanic contractions and initially potentiated but later depressed twitches, (2) abolished the action potential overshoot, and (3) shifted peak K+ contracture tension to more positive membrane potentials. Twitch and tetanic contractions, and action potentials remained depressed when Cd2+ was washed out of the bath. The effects of Cd2+ on the twitch, tetanus and action potential were mimicked by Zn2+, while La3+ and Co2+ at 3 mM - or Mg2+ and Ca2+ at 30 mM - depressed peak twitch and tetanic tension, but did not potentiate twitches. The results suggest that: (1) Cd2+ and Zn2+ potentiate twitch tension by prolonging action potential depolarisation; (2) Cd2+ depresses twitch and tetanic tension by reducing the action potential overshoot, and causing a positive shift in the voltage dependence of contraction; and (3) the irreversible depression of action potential amplitude in rat soleus muscle is a specific property of Cd2+ and Zn2+ that is not shared by Co2+, Mg2+ or Ca2+.
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PMID:Effects of external cadmium ions on excitation-contraction coupling in rat soleus fibres. 992 59

The effect of a conditioning depolarizing current pulse (80-200 micros) on quantal secretion evoked by a similar test pulse at another site was examined in visualized motor-nerve terminal branches of amphibian endplates (Bufo marinus). Tetrodotoxin (200 nM) and cadmium (50 microM) were used to block voltage-dependent sodium and calcium conductances. Quantal release at the test electrode was depressed at different distances (28-135 microm) from the conditioning electrode when the conditioning and test pulses were delivered simultaneously. This depression decreased when the interval between conditioning and test current pulses was increased, until, at an interval of approximately 0.25 ms, it was negligible. At no time during several thousand test-conditioning pairs, for electrodes at different distances apart (28-135 microm) on the same or contiguous terminal branches, did the electrotonic effects of quantal release at one electrode produce quantal release at the other. Analytic and numerical solutions were obtained for the distribution of transmembrane potential at different sites along terminal branches of different lengths for current injection at a point on a terminal branch wrapped in Schwann cell, in the absence of active membrane conductances. Solutions were also obtained for the combined effects of two sites of current injection separated by different time delays. This cable model shows that depolarizing current injections of a few hundred microseconds duration produce hyperpolarizations at approximately 30 microm beyond the site of current injection, with these becoming larger and occurring at shorter distances the shorter the terminal branch. Thus the effect of a conditioning depolarizing pulse at one site on a subsequent test pulse at another more than approximately 30 microm away is to substantially decrease the absolute depolarization produced by the latter, provided the interval between the pulses is less than a few hundred microseconds. It is concluded that the passive cable properties of motor nerve terminal branches are sufficient to explain the effects on quantal secretion by a test electrode depolarization of current injections from a spatially removed conditioning electrode.
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PMID:Quantal secretion and nerve-terminal cable properties at neuromuscular junctions in an amphibian (Bufo marinus). 1008 40

1. Using whole-cell patch clamp recording from neurones in an in vitro slice preparation, we have examined opioid- and orphanin FQ (OFQ)-mediated modulation of synaptic transmission in the rat arcuate nucleus and ventromedial hypothalamus (VMH). 2. Application of OFQ activated a Ba2+-sensitive and inwardly rectifying K+ conductance in approximately 50 % of arcuate nucleus neurones and approximately 95 % of VMH neurones. The OFQ-activated current was blocked by the nociceptin antagonist [Phe1Psi(CH2NH)Gly2]-nociceptin(1-13) NH2 (NCA), a peptide that on its own exhibited only weak agonist activity at high concentrations (> 1 microM). Similar current activation was observed with the mu agonist DAMGO but not delta (DPDPE) or kappa (U69593) agonists. 3. In arcuate nucleus neurones, DAMGO (1 microM), U69593 (1 microM) and OFQ (100 nM to 1 microM) but not DPDPE (1 microM) were found to depress the amplitude of electrically evoked glutamatergic postsynaptic currents (EPSCs) and decrease the magnitude of paired-pulse depression, indicating that opioid receptors were located presynaptically. 4. In VMH neurones, DAMGO strongly depressed the EPSC amplitude in all cells examined. DAMGO decreased the magnitude of paired-pulse depression, indicating that mu receptors were located presynaptically. U69593 weakly depressed the EPSC while OFQ and DPDPE had no effect. 5. In VMH neurones, DAMGO depressed the frequency of miniature EPSCs (-58 %) in the presence of tetrodotoxin and Cd2+ (100 microM), suggesting that the actions of mu receptors could be mediated by an inhibition of the synaptic vesicle release process downstream of Ca2+ entry. 6. The data presented show that presynaptic modulation of excitatory neurotransmission in the arcuate nucleus occurs through mu, kappa and the orphan opioid ORL-1 receptors while in the VMH presynaptic modulation only occurs through mu opioid receptors. Additionally, postsynaptic mu and ORL-1 receptors in both the arcuate nucleus and VMH modulate neuronal excitability through activation of a K+ conductance.
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PMID:Pre- and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro. 1033 93

A number of studies documented that the heavy metals are not only toxic for the organisms but they may modulate immune responses. The immunomodulatory activity was proved in several in vivo and in vitro model systems. In the current study, immunomodulatory activities of lead and cadmium are presented. The viability of both lymphocytes and macrophages was affected by heavy metals in a dose- and time-dependent manner. In the case of lead, the depression of N-oxide production closely correlated with increased blast transformation of spleen cells induced by concanavalin A (ConA). On the contrary, cadmium suppressed the production of N-oxides but stimulated significantly the proliferation of spleen cells. The production of cytokines by lymphocytes and macrophages was dependent on the in vitro model used. Generally, the treatment of macrophages with lead results in disregulation of the production of proinflammatory cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha) and interleukin 6 (IL-6)] and preferential production of Th1 type of cytokines (IFN-gamma and IL-2). Cadmium seemed to trigger the Th2 cytokine regulatory pathway [interleukin 4 (IL-4), interleukin 10 (IL-10)]. The results suggest the metal-induced changes in immunoregulatory mechanism of host with potentially severe clinical consequences.
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PMID:The immunomodulatory effect(s) of lead and cadmium on the cells of immune system in vitro. 1069 59

Wadi El Raiyan is a great depression located southwest of Cairo in the western desert of Egypt, one of the most arid regions of the world. In 1973, Wadi El Raiyan was connected with the agricultural wastewater drainage system of the El Faiyum province to provide a reservoir for the wastewater that exceeded the capacity of Lake Qarun north of the province. Pollutants from agricultural waste including pesticides and fertilizers as well as other effluents of industrial activities and runoffs certainly will pass into the biotic elements of the ecosystem. This report presents the status of inorganic pollutants including anions, cations, and trace metals in the two lakes and the surrounding springs of Wadi El Raiyan using ion chromatography, ion-selective electrodes, and inductively coupled plasma emission spectroscopy. The report also includes the levels of selected metals in the vegetation community of the area. The result of this investigation revealed a great improvement in water quality of the Wadi El Raiyan lakes compared to 1988 report by Saleh et al. Mercury was not detected in any of the samples and the level of lead was significantly reduced. Cadmium levels were much higher than those seen earlier. The higher level of cadmium might be used as an indicator to track the contamination of water by human waste. Concentrations of common anions were not significantly different from those reported earlier. However, an increase in the level of cyanide was observed. Levels of heavy metals in vegetation around the lakes were also found to be lower than previously reported.
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PMID:Monitoring Wadi El Raiyan lakes of the egyptian desert for inorganic pollutants by ion-selective electrodes, ion chromatography, and inductively coupled plasma spectroscopy. 1070 52

1. Modulation of release probability is a major factor underlying short-term synaptic plasticity in the central nervous system. We have investigated the relationship between release probability ((Pr) and paired-pulse modulation at a large auditory calyceal synapse containing many transmitter release sites. Whole-cell patch electrode recordings were made of excitatory postsynaptic currents (EPSCs), evoked by stimulation of auditory nerve fibres giving rise to the endbulbs of Held. 2. Quantitative estimates of Pr and quantal amplitude were obtained using the recently developed variance-mean analysis technique. Release probability conditions were modulated by bath application of cadmium, elevated calcium and protein kinase C activation by phorbol esters. 3. Our results show that, under physiological conditions, most sites released neurotransmitter following a single presynaptic nerve impulse, with a mean Pr of 0.6. The mean quantal amplitude was 44 pA, which was consistent with the mean amplitude of miniature EPSCs (47 pA). 4. Under high release probability conditions with elevated calcium or phorbol esters, Pr at all sites approached 1.0. At these high Pr values, variance-mean analysis indicated a significant postsynaptic contribution to paired-pulse depression. The miniature EPSC amplitudes were decreased following stimulation in elevated calcium, confirming a postsynaptic component of paired-pulse depression at this glutamatergic connection. 5. A notable feature was the large variability between neurons in the relationship between paired-pulse ratio and Pr. Based on current models of vesicle release and ultrastructural evidence, we suggest that this variability may be partly due to morphological differences between endbulb specializations, particularly in the ratio of fusion-ready to reserve populations of vesicles at endbulb release sites.
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PMID:Release probability modulates short-term plasticity at a rat giant terminal. 1076 30

The influence of CdCl(2), used at 1, 10 and 100 microM concentration, and ZnCl(2) at 1, 10 and 100 microM concentration on the production of interferon (IFN) and tumor necrosis factor (TNF) in bovine aorta endothelial cells (BAECs) was examined. BAECs were treated with cadmium ions or zinc ions alone or together with cytokine inducers: Newcastle disease virus (NDV) and lipopolysaccharide (LPS). Cadmium ions at 1 and 10 microM concentration, used alone induced a low, but detectable TNF activity in BAECs, and zinc ions at 1, 10 and 100 microM concentration induced both IFN and TNF activity. In contrast to that, cadmium added to BAECs together with the virus or LPS as cytokine inducers significantly inhibited the production of IFN and TNF. Cadmium effect depended on the concentration used, and 1 and 10 microM CdCl(2) partially, but 100 microM cadmium completely inhibited the production of both cytokines. Zinc ions at 1 and 10 microM concentration, which only slightly inhibited the production of both cytokines, did not reconstitute cadmium-depressed IFN and TNF production. These data indicate that cadmium-induced depression of cytokine production in bovine endothelial cells, in response to viral and bacterial stimuli, cannot be reversed by zinc supplementation.
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PMID:The influence of cadmium and zinc ions on the interferon and tumor necrosis factor production in bovine aorta endothelial cells. 1077 Nov 38

High pressure induces CNS hyperexcitability while markedly depressing synaptic transmitter release. We studied the effect of pressure (up to 10.1 MPa) on the parallel fibre (PF) synaptic response in biplanar cerebellar slices of adult guinea pigs. Pressure mildly reduced the PF volley amplitude and to a greater extent depressed the excitatory field postsynaptic potential (fPSP). The depression of the PF volley was noted even at supramaximal stimulus intensities, indicating an effect of pressure on the amplitude of the action potential in each axon. Low concentrations of TTX mimicked the effects of pressure on the PF volley without affecting the fPSP. Application omega-conotoxin GVIA (omega-CgTx) reduced the synaptic efficacy by 34.3+/-2.7%. However, in the presence of omega-CgTx the synaptic depression at pressure was significantly reduced. Reduced Ca2+ entry by application of Cd2+ or low [Ca2+]o did not have a similar influence on the effects of pressure. Application of omega-AGA IVA, omega-AGA TK and Funnel-web spider toxin did not affect the synaptic response in concentrations that usually block P-type Ca2+ channels, whilst the N/P/Q-type blocker omega-conotoxin MVIIC reduced the response to 52.7+/-5.0% indicating the involvement of Q-type channels and R-type channels in the non-N-type fraction of Ca2+ entry. The results demonstrate that N-type Ca2+ channels play a crucial role in the induction of PF synaptic depression at pressure. This finding suggests a coherent mechanism for the induction of CNS hyperexcitability at pressure.
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PMID:Pressure-induced depression of synaptic transmission in the cerebellar parallel fibre synapse involves suppression of presynaptic N-type Ca2+ channels. 1106 97


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