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)

The mechanism of inhibition of HCO3 transport by parathyroid hormone (PTH) in the proximal tubule is not clearly defined. Previous studies in vitro have suggested that this effect is mediated via cAMP generation, which acts to inhibit Na/H exchange, resulting in cell acidification. To examine this question in vivo, intracellular pH (pHi) was measured in the superficial proximal tubule of the rat using the pH-sensitive fluoroprobes 4-methylumbelliferone (4MU) and 2',7'-bis(carboxyethyl)-(5, and 6)-carboxyfluorescein (BCECF). PTH was found to alkalinize the cell. This alkalinization suggested inhibition of basolateral base exit, which was confirmed by in situ microperfusion studies: lowering HCO3 in peritubular capillaries acidified the cell, an effect blunted by PTH. Removal of luminal Na promoted basolateral base entry, alkalinizing the cell. This response was also blunted by PTH. Readdition of luminal Na stimulated the luminal Na/H exchanger, causing an alkalinization overshoot that was partially inhibited by PTH. cAMP inhibited luminal H secretion but did not alkalinize the cell. Stimulation of phosphatidylinositol-bis-phosphate turnover by PTH was suggested by the effect to the hormone to increase cell Ca. Blocking the PTH-induced rise in cell Ca blunted the effect of the hormone to alkalinize the cell, as did inhibition of phosphatidylinositol breakdown. Furthermore, stimulation of protein kinase C by a phorbol ester and a diacylglycerol applied basolaterally alkalinized the cell and inhibited luminal H secretion. The findings indicate that both arms of the phosphatidylinositol-bis-phosphate cascade play a role in mediating the effect of PTH on the cell pH. The results are consistent with the view that PTH inhibits base exit in the proximal tubule by activation of the phosphatidylinositol cascade. The resulting alkalinization may contribute, with cAMP, to inhibit apical Na/H exchange and the PTH-induced depression of proximal HCO3 reabsorption.
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PMID:Parathyroid hormone decreases HCO3 reabsorption in the rat proximal tubule by stimulating phosphatidylinositol metabolism and inhibiting base exit. 131 50

1. Active sodium (Na+) and chloride (Cl-) fluxes were studied in vitro in Ussing-type chambers with stripped jejunal mucosa of piglets which suffered from pseudo-vitamin D deficiency rickets, type I. The piglets are devoid of renal calcitriol (1,25-dihydroxy vitamin D3) production and have only small amounts of calbindin in their jejunal enterocytes. 2. In the presence of 0.01 mM-indomethacin non-stimulated short-circuit current (Isc), transepithelial potential difference (PD), tissue conductance (Gt) and unidirectional Na+ (JNa) and Cl- fluxes (JCl) were not affected by the low calcitriol (LC) concentration in plasma. 3. Adding 10 mM-theophylline to the serosal solution in the presence of 0.01 mM-indomethacin caused significantly greater increases in Isc in LC mucosa than in mucosa of vitamin D3-treated and control piglets with normal calcitriol (NC) concentrations in plasma. Omission of indomethacin significantly increased Isc stimulation provoked by theophylline with LC and NC mucosa. The increase, however, was significantly greater with LC than with NC mucosa. 4. Omission of calcium (Ca2+) from the serosal bathing solution significantly depressed Isc stimulation by 10 mM-theophylline in indomethacin-treated LC and NC mucosa. But depression was greater with LC than with NC mucosa. 5. Blocking Ca2+ entry into the cytosol by adding either 0.1 mM-TMB-8 or 0.5 mM-d,l-verapamil to the serosal bathing solution abolished the difference in Isc response to theophylline between indomethacin-treated LC and NC mucosa due to greater depression of Isc in LC than in NC mucosa. 6. The combined effects of theophylline and A23187 on Isc stimulation were calcitriol dependent. In the presence of indomethacin this dependence was only significant when A23187 was given prior to theophylline. In the absence of indomethacin the combined effects of A23187 and theophylline on Isc were always significantly greater in LC than in NC mucosa, irrespective of the order of adding the two agents. 7. Addition of theophylline stimulated net Na+ and Cl- secretion in indomethacin-treated LC and NC mucosa. The increases of net Na+ and Cl- fluxes fully accounted for the rise of Isc with NC mucosa but accounted only partly for the increase in Isc with LC mucosa. This resulted in significant increase in theophylline-stimulated residual ion flux (JR) in LC mucosa which probably resulted from enhanced secretion of bicarbonate.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of calcitriol on stimulation of ion transport in pig jejunal mucosa. 184 52

The hemodynamic effects of intravenous class I and class IV antiarrhythmic drugs were investigated at different doses in comparison. In open-chest rats hemodynamic measurements in the intact circulation and isovolumic registrations 5 min after infusion of flecainide (2, 4, 8 mg/kg), disopyramide (1, 2, 4, 8 mg/kg), quinidine (5 and 10 mg/kg) and verapamil (0.35, 0.7, 1.5 mg/kg) were compared to saline controls. After clinically usual doses all investigated drugs had no effects on stroke volume, cardiac output, dp/dtmax and systemic resistance. The isovolumic pressure generating capacity of the left ventricle was not decreased at these doses. High intravenous doses of the drugs, however, caused a significant depression of myocardial performance (pressure generating capacity). Furthermore, flecainide decreased mean aortic pressure and heart rate, while disopyramide had no significant effect on the peripheral circulation. Blocking of the autonomic system (1 mg/kg propranolol and 0.1 mg/kg atropine) did not change significantly the action of disopyramide. Quinidine lowered heart rate and pressures. Verapamil reduced the heart rate and tended to decrease the mean aortic pressure. Besides the negative inotropic action of high doses the different hemodynamic profiles of class I and class IV antiarrhythmic drugs might be of importance for intravenous application in patients with left ventricular dysfunction.
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PMID:Circulatory and myocardial effects of different sodium antagonistic drugs in comparison to the calcium antagonist verapamil. 251 61

The clinical observations on alexithymia which were initiated by Sifneos and Nemiah in the earlier 1970s have given rise to a host of studies with implications beyond the psychosomatic field of enquiry. Is alexithymia a pathology of affect or a character neurosis; is it primary or secondary; genetic or developmental? Is it an adaptational deformation related to social class and low psychological sophistication, a life style or a cerebral deficit? Is it global and consistent (trait) or partial and temporary (state)? Is it part of the necessary and sufficient condition for the development of a psychosomatic symptom or is it a nonspecific autoplastic alteration? It is quite possible that alexithymia is one of several mediating processes between stress and disease along with genetic susceptibility, developmental variables, context and reaction to untoward life events, coping dispositions, psychosocial support and sociocultural factors. Therapeutic approaches would depend on whether we are dealing with a primary affectless condition or a secondary one. A differential diagnosis is essential since self-numbing following psychic trauma or a pathological grief, masked and atypical depression are treatable. Blocking of affect may have dire effects on the psychosomatic economy and on the capacity for intimacy. Muscular and psychological rigidity, weariness, ennui and anhedonia may be the only clues to the presence of alexithymia. Since we may be dealing with a spectrum disorder, there is no single treatment modality. There are no controlled studies on the use of psychotropic drugs and psychoanalytic-oriented and behavioral approaches have been shown to be of some benefit.
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PMID:Alexithymia, clinical and therapeutic aspects. 360 41

Blocking of sympathetic conduction aims at permanent or temporary elimination of those pain pathways conducted by the sympathetic nervous system. In order to provide an objective evaluation of sufficient blocking effect, earlier inquiries referred to parameters such as: (1) observation of clinical signs such as Horner's syndrome, Guttman's sign, anhidrosis, extended venous filling; (2) difference in skin temperature of at least 1.5 degrees C between blocked and unblocked side; (3) increase in amplitude of the pulse wave; and (4) depression of the psychogalvanic reflex (PGR) on the blocked side (Fig. 1). In clinical practice, these control parameters are effective because they are time-saving, technically simple, and highly evidential. Further parameters for evaluating sympathetic blockade are examination of hydrosis by means of color indicators such as bromocresol and ninhydrin, oscillometry, and plethysmography. The effectiveness of sympathetic blockade after stellate ganglion and sympathetic trunk blocks has been verified by various authors. In a clinical study, 16 patients were divided into four groups in order to test the effectiveness of sympathetic blockade after spinal anesthesia with 3 ml 0.75% bupivacaine (group I) and 4 ml 0.75% bupivacaine (group II) and after peridural anesthesia with 15 ml 0.75% bupivacaine (group III) and 20 ml 0.75% bupivacaine (group IV) by means of temperature difference, response of pulse wave amplitude and PGR between blocked lower and unblocked upper extremity, and sensory levels of block. The patients were classified as ASA I and II; their ages varied from 20 to 63 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effectiveness of sympathetic block using various technics]. 365 38

1. An electrophysiological analysis has been made of the uptake of NAd in the sympathetic nerve terminals of the isolated vas deferens of the mouse. The amplitude of the excitatory junction potentials (e.j.p.s) recorded intracellularly in smooth muscle cells was taken as a measure of the NAd output per impulse from the terminals of sympathetic axons.2. Neuronal uptake blockers (desipramine and cocaine) greatly depressed the amplitude of all e.j.p.s after the first in a short train (< 100) at high frequencies (>/= 1 Hz).3. Blocking neuronal uptake did not affect the time course of decline in amplitude of the e.j.p. during long trains of stimulation over several minutes, apart from the immediate depression in the e.j.p. following the first few impulses.4. The time course of decline of the e.j.p. amplitude during continual stimulation, when both neuronal uptake and synthesis was blocked, was similar to that when only synthesis was blocked, apart from the immediate depression following the first few impulses.5. Phenoxybenzamine reversed the normal depression in e.j.p. amplitude observed at high frequencies (>/= 1 Hz) to facilitation. This facilitation lasted for several minutes of high frequency stimulation.6. A model has been proposed of the sympathetic nerve terminal, in which NAd is released by each nerve impulse in a train from a small pool in the nerve terminal, which is principally replenished by uptake of the NAd released by the immediately preceding impulses in the train. The pool is replenished to a less extent by transmitter located in two stores in the terminal which are in turn replenished by transmitter synthesis.
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PMID:An electrophysiological analysis of the uptake of noradrenaline at sympathetic nerve terminals. 472 36

Patients with aplastic anemia were tested for natural killer (NK) activity, and the roles of granulocytes and granulocyte colony-stimulating factor (G-CSF) in the regulation of cytotoxicity were evaluated. Blood lymphocytes showed low or no NK activity against K562 targets. The depression of NK activity was more frequently recorded for patients who were not in remission and those who received G-CSF administration. Granulocytes of aplastic anemia patients with impaired NK activity suppressed the lytic activity of NK cells. By contrast, granulocytes from normal controls and aplastic anemia patients with normal NK activity had no suppressive activity. There was a good correlation between NK activity of lymphocytes and suppressive activity of granulocytes. Blocking of direct contact of suppressor and effector cells by cell chambers abolished suppression of cytotoxicity. NK suppression by granulocytes was resistant to treatment with catalase or superoxide dismutase. In vitro stimulation with G-CSF of granulocytes that naturally had no suppressive activity resulted in development of suppressive function, whereas granulocytes with natural suppressive activity were not further stimulated in vitro by G-CSF to express augmented activity. These results suggest that the presence of suppressor granulocytes in the blood could be one cause of the impaired NK activity in patients with aplastic anemia.
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PMID:Suppression of natural killer cell activity by granulocytes in patients with aplastic anemia: role of granulocyte colony-stimulating factor. 751 63

The effects of plant diterpenes, horminone (HMN) and taxodione (TXN), on the GABAA receptor-operated Cl-current (IGABA) were investigated in voltage-clamped and internally perfused neurones dissociated from frog dorsal root ganglia. Both diterpenes depressed IGABA in a concentration-dependent manner similar to that of picrotoxin. Concentrations required to elicit 50% depression of the IGABA were 10(-6) M for picrotoxin, 10(-5) M for HMN and 10(-4) M for TXN. Blocking and restoration kinetics of the IGABA with HMN were also similar to those of picrotoxin. Time constants for both the blockade and restoration of the IGABA with TXN were more than five times greater than those with HMN.
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PMID:Effects of plant diterpenes on the neuronal GABAA receptor-operated chloride current. 769 6

To detect what initiates spreading depression (SD), the early prodromal events were investigated in hippocampal CA1 of urethane-anesthetized rats. SD was provoked by microdialysis or focal microinjection of high-K+ solution. Extracellular DC potentials and extracellular potassium concentration ([K+]o) were recorded, and spontaneous and evoked potentials analyzed for current source-density (CSD). In the front of an approaching SD wave, several seconds before the onset of the typical sustained negative potential shift (delta Vo) and the increased [K+]o, fast electrical activity was detected. This consisted initially of small rhythmic (60-70 Hz) sawtooth wavelets, which then gave way to a shower of population spikes (PSs) of identical frequency. Prodromal wavelets and PSs were synchronized over considerable distances in the tissue. Sawtooth wavelets were identified as pacemakers of the prodromal PS burst. Simultaneous recording at three depths revealed that the spontaneous prodromal PSs occurred exactly in phase in dendrites and somata whereas synaptically transmitted PSs arose first in the proximal dendrites and were conducted from there into the soma membrane. During a spike burst, stratum (st.) pyramidale served as current sink, while in the proximal sublayer of st. radiatum spike-sinks gave way to spike sources that grew larger as the sinks in st. pyramidale began to subside. Blocking synaptic transmission did not abolish the prodromal spike burst, yet repetitive orthodromic activation inhibited it without altering the subsequent SD waveform. Complex changes in cell excitability were detected even before fast spontaneous activities. We concluded that, in the initial evolution of SD, changes in neuron function precede the regenerating depolarization by several seconds. We propose that the opening of normally closed electric junctions among neurons can best explain the long-distance synchronization and the flow current that occurs in the leading edge of a propagating wave of SD.
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PMID:Role of neuronal synchronizing mechanisms in the propagation of spreading depression in the in vivo hippocampus. 796

1. A study has been made of the modulation of high-voltage activated transient and sustained calcium currents in cultured neurones of avian ciliary ganglia by nitric oxide (NO) and arachidonic acid. 2. Sodium nitroprusside (100 microM) reduced the transient calcium current (ICa) on average by 31% and the sustained ICa by 32% during a test depolarization to +20 mV from a holding potential of -100 mV. This reduction was maintained for at least 30 min following a single application of sodium nitroprusside. 3. L-Arginine (270 microM) reduced the transient ICa on average by 28% and the sustained ICa by 22% and these effects were prevented by the presence of the NO-synthase competitive blocker NG-nitro-L-arginine methylester (L-NAME; 100 microM) in the bathing solution. 4. Arachidonic acid (50 microM) reduced the transient ICa on average by 28% and the sustained ICa by 33%. When added together, arachidonic acid (50 microM) and L-arginine (270 microM) produced the same effects as arachidonic acid alone. 5. Blocking the conversion of arachidonic acid to prostaglandins by addition of indomethacin (20 microM) to the bathing solution did not prevent the depression of either the transient or the sustained calcium current during application of arachidonic acid (50 microM). The effects of arachidonic acid were also not occluded by L-NAME (100 microM) when present in the bathing solution. 6. Inhibiting the biosynthesis of leukotrienes by applying L-663,536 (MK-886; 3 microM) to the bathing solution prevented the depression of both components of ICa during application of arachidonic acid (50 microM). 7. These results indicate that endogenous NO and arachidonic acid pathways are present in parasympathetic ciliary neurones, and that both act to depress high-voltage, gated, calcium channel activity.
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PMID:Nitric oxide and arachidonic acid modulation of calcium currents in postganglionic neurones of avian cultured ciliary ganglia. 839 90


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