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)

1. Responses of single cells in the isolated cat spinal ganglion to GABA applied by superfusion or by iontophoresis were recorded using intracellular micro-electrodes. 2. Of the twelve structurally related compounds investigated, GABA was the most effective in its ability to produce a depolarization of the cell membrane. 3. Studies determining concentration-response relationships indicate that two to three molecules of GABA are required to combine with the GABA receptor for activation. 4. Bicuculline and picrotoxin, each act in a non-competitive manner to antagonize the GABA-induced membrane current. 5. The equilibrium potential for iontophoretically induced GABA depolarizations (EGABA) was found to be -23.5 plus or minys 6.1 mV. EGABA was independent upon [cl-]o, but independent of [Na+]o, [K+], or [Ca2+]o. 6. Intracellular injection of twenty antions (Br-, I-, NO2-, NO3-, ClO4-, SCN-, Bf4-, HS-, OCN-, ClO3-, BrO3-, F-, HCO2-, HSO3-, HCO3-, CH3CO2-, SO42-, C6H5O73-) indicated that the activated GABA receptor membrane was permeable to those anions whose hydrated diameter is no larger than that of ClO-3. 7. Restoration of the GABA depolarization to its control level after augmentation by Cl- injection had a mean time constant of 27.8 plus or minus 2.6 min. Picrotoxin did not alter this value. 8. When foreign anions were exchanged for Cl- in the perfusion solution, the ten anaions smaller or equal to ClO3-, decreased the GABA depolarization by 50-90% and increased its time course 1.5-2.0 x control. The only exception having a small radius was Br- which augmented the amplitude 10-30%. 9. The ten anions larger than ClO3- produced a biphasic effect, i.e. an initial augmentation followed by a marked (up to 100%) depression of the response. Experiments with CH3COO-, CH3SO4-, or HOCH2CH2SO3-, indicated that this depression was non-competitive.
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PMID:Characterization and ionic basis of GABA-induced depolarizations recorded in vitro from cat primary afferent neurones. 63 14

The manner of inhibition of thyroid I- accumulation by perchlorate (CIO4-) and thiocyanate (SCN-) was studied using a newly developed biological model of the I- transport system. CIO4- inhibited I- accumulation in phospholipid vesicles made from thyroid plasma membrane and soybean phospholipids by decreasing Na+-dependent I- influx. The anion did not at all induce I- leakage from the vesicles. On the basis of Lineweaver-Burk plot analysis, it did not change Vmax for I- concentration. These results suggest that CIO4- is a competitive inhibitor of thyroid I- transport. In contrast, SCN- did increase I- leakage from the phospholipid vesicles to diminish I- accumulation. This anion might cause only slight depression of Na+-dependent I- entry, if any. The results do not support the idea that SCN- may be a competitive inhibitor, in spite of the fact that the anion did not change Vmax for I- transport on the basis of Lineweaver-Burk plot analysis.
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PMID:Inhibition of iodide accumulation by perchlorate and thiocyanate in a model of the thyroid iodide transport system. 631 92

Previous studies have shown that stressors modify endogenous opioid systems. However, the consequences of social stress on the function of endogenous opioid systems is not well documented. The present studies investigated the effect of rank and housing condition on response to SNC-80, a delta receptor agonist. Triad-housed rats were assessed for dominance status by their behavior and alteration in body weights. At 3 and 50 days, triad- and individually housed rats were injected with SNC-80 (35 mg/kg i.p.) or saline, and evaluated using a test battery consisting of open field behaviors, rectal temperature, analgesia, and air-puff-induced ultrasonic vocalizations. After 50 days of housing, plasma corticosterone, adrenal catecholamines, and the density of cyclic[D-penicillamine2-D-penicillamine2]enkephalin-stimu lat ed guanylyl 5'-[gamma[35S]thio]-triphosphate binding in the prefrontal cortex, the amygdala, nucleus accumbens, thalamus, arcuate, and median eminence were also determined. The first 24 h of triad housing resulted in loss of body weight in subdominant (betas and gammas) but not dominant alpha rats. SCN-80-induced hypothermia was smaller, and there was no depression of headpoke and locomotor behavior in the periphery and the center of the field of alpha rats, in contrast to subdominant and singly housed rats. Rank status did not influence SNC-80's analgesic effect or its inhibition of air-puff-induced ultrasonic vocalizations. Plasma corticosterone levels of alphas and gammas were lower compared with betas and singly housed rats. Agonist stimulation of delta receptor guanylyl 5'-[gamma[35S]thio]-triphosphate binding was lateralized in prefrontal cortex and amygdala, but not nucleus accumbens. Binding was highest in all brain areas of singly housed rats and lowest in the thalamus of beta and of gamma rats. Lateralized binding in amygdala, high locomotor activity, and sensory sensitivity correlated positively with greater sensitivity to SNC-80-induced depression in these measures. Higher binding in the right amygdala correlated with higher plasma corticosterone levels. These findings indicate that dominant rats displayed stimulant rather than depressant responses to delta-opioid activation. Therefore in rodents rank-related stress can alter responsiveness of the endogenous opioid system, and dominance can increase the excitatory effects of delta agonists.
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PMID:Effect of chronic social stress on delta-opioid receptor function in the rat. 1038 76

This article presents the universal challenge for identification of risk factors of elderly malnutrition. An estimated 14.2% increase among the elderly population was predicted by the year 2025 in the Americas. Several factors determine the proportion of older persons in a population, such as the health history of the country over the past century, the current state of economy and percentage of total gross domestic product allocated to health services, and the adequacy and of the health system and investments made on it. Common types of malnutrition seen in elderly persons are undernutrition, vitamin and mineral deficiencies and excesses, obesity, nutritional imbalances and toxicities. These can be attributed to poor dietary intake and diseases. Risk factors for poor nutritional status involve socioeconomic status, mental and physical functioning, culture and social situation, food access, health status, health behavior and environmental health. Promotion and implementation of appropriate interventions in ameliorating nutritional problems include enhancement of dietary intakes, more physically active lifestyles, and improvements in health care, social support, and food assistance. This paper suggests 1) implementing prevention-oriented programs for elders; 2) increasing the years of health life by program activities on the prevention of age-associated chronic degenerative diseases; 3) eliminating vaccine-preventable diseases; 4) eradicating poverty-related undernutrition and malnutrition; and 5) ameliorating loneliness and depression. In addition, the call for prevention, recognition, and improvement of nutritional status by health care providers was emphasized.
SCN News 1999 Dec
PMID:Identifying elders at risk of malnutrition: a universal challenge. 1229 2

The cellular expression of nitric oxide synthase (NOS) was studied in neurons of the Nuc. suprachiasmaticus (SCN) of depressed patients and matched controls. The number of NOS-immunoreactive SCN neurons was significantly reduced in depression. We conclude that affective disorders are accompanied by impaired hypothalamic NO signaling.
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PMID:Further immunohistochemical evidence for impaired NO signaling in the hypothalamus of depressed patients. 1248 41

SCN- binds to the charged amino group of lysines, inducing local changes in the electrostatic free energy of histones. We exploited this property to selectively perturb the histone-DNA interactions involved in the stabilization of eu and heterochromatin. Differential scanning calorimetry (DSC) was used as leading technique in combination with trypsin digestion that selectively cleaves the histone end domains. Euchromatin undergoes progressive destabilization with increasing KSCN concentration from 0 to 0.3 M. Trypsin digestion in the presence of 0.2 M KSCN show that the stability of the linker decreases as a consequence of the competitive binding of SCN- to the amino groups located in the C and N-terminal domain of H1 and H3, respectively; likewise, the release of the N-terminal domain of H4 induces an appreciable depression in both the temperature and enthalpy of melting of core particle DNA. Unfolding of heterochromatin requires, in addition to further cleavage of H4, extensive digestion of H2A and H2B, strongly suggesting that these histones stabilize the higher order structure by forming a protein network which extends throughout the heterochromatin domain.
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PMID:SCN- binding to the charged lysines of histones end domains mimics acetylation and shows the major histone-DNA interactions involved in eu and heterochromatin stabilization. 1625

Anion affinities, gammaX-, for the aerial interface of aqueous (Br- + NO3- + I- + SCN- + BF4- + ClO4-) solutions are determined by electrospray ionization mass spectrometry. The composition of the ions ejected from the surface of fissioning nanodroplets shows that gammaX- increase (decrease) exponentially with anionic radii, aX-(dehydration free energies, dGX-), and selectively respond to the presence of surfactants. BF4-, the least hydrated and polarizable anion of the set, has one of the largest gammaX- values. Non-ionic surfactants decrease gammaI- and gammaSCN- but increase gammaBF4-. Cetyltrimethyl ammonium markedly enhances the gammaX- of smaller anions. A similar but weaker effect is observed upon lowering the pH of the bulk solutions from 8.2 to 3.0. Dodecyl sulfate has a negligible effect on gammaX-. Considering that (i) universal many-body electrodynamic interactions will progressively stabilize the interfacial layer as its dielectric permittivity falls relative to that of the bulk solution and (ii) water permittivity is uniformly depressed by increasing concentrations of these anions, we infer that the observed Hofmeister correlation, ln gammaX- infinity - dGX-, is consistent with the optimal depression of the permittivity of the drier interfacial layer by the least hydrated ions. Interfacial ion-ion interactions can significantly influence gammaX- in environmental aqueous media.
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PMID:Experimental anion affinities for the air/water interface. 1718 Nov 93

Aging affects several processes modulated by the 5-HT(7) receptor subtype, including circadian rhythms, learning and memory, and depression. Previously, we showed that aging induces a decrease in the hamster dorsal raphe (DRN) in both 5-HT(7) receptor binding and circadian phase resetting responses to 8-OH-DPAT microinjection. To elucidate the mechanisms underlying the aging decrease in 5-HT(7) receptors, we investigated aging modulation of 5-HT(7) receptor mRNA expression in the DRN, brain regions afferent to the DRN, and brain regions regulating circadian rhythms or memory. In situ hybridization for 5-HT(7) receptor mRNA was performed on coronal sections prepared from the brains of young, middle-aged, and old male Syrian hamsters. 5-HT(7) receptor mRNA expression was quantified by densitometry of X-ray film autoradiograms. The results showed that aging did not significantly affect 5-HT(7) receptor mRNA expression in the DRN or most other brain regions examined, with the exception of the cingulate cortex and paraventricular thalamic nucleus. Within the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals, 5-HT(7) receptor mRNA expression was localized in a discrete subregion resembling the calbindin subnucleus previously described. A second experiment using adjacent tissue sections showed that 5-HT(7) receptor mRNA and calbindin mRNAs were concentrated in the same region of the SCN, and as well as in the same region of several other brain structures. The localization of 5-HT(7) receptors and calbindin mRNAs within the same regions suggests that the proteins they encode may interact to modulate processes such as circadian timekeeping.
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PMID:Expression of 5-HT7 receptor mRNA in the hamster brain: effect of aging and association with calbindin-D28K expression. 1730 Jul 62

In all living organisms, one of the most indispensable biological functions is the circadian clock (suprachiasmatic nuclei; SCN), which acts like a multifunction timer to regulate homeostatic systems such as sleep and activity, hormone levels, appetite, and other bodily functions with 24h cycles. Circadian rhythms regulate diverse physiologic processes, including homeostatic functions of steroid hormones and their receptors. Perturbations of these rhythms are associated with pathogenic conditions such as depression, diabetes and cancer. Clock genes are identified as the genes that ultimately control a vast array of circadian rhythms in physiology and behavior. Clock gene regulates several diseases such as cancer, metabolic syndrome and sleep etc. CLOCK mutation affects the expression of rhythmic genes in wild-type (WT) tissue, but also affects that of non-rhythmic genes. On the other hand, the change of the drug pharmacodynamic and pharmacokinetic (PK/PD) parameters are influenced by not only inter-individual variability but also intra-individual variabilities of medications. Identification of a rhythmic marker for selecting dosing time will lead to improved progress and diffusion of chronopharmacotherapy. The mechanisms underlying chronopharmacological findings should be clarified from viewpoint of clock genes. On the other hand, several drugs have an effect on molecular clock. Thus, the knowledge of intra- and inter-individual variability of molecular clock should be applied for the clinical practice. Therefore, we introduce the regulatory system of biological rhythm from viewpoints of clock genes and the possibility of pharmacotherapy based on the intra- and inter-individual variability of clock genes.
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PMID:Chronopharmacological strategies: Intra- and inter-individual variability of molecular clock. 2063 41

There are morphofunctional zones in organism tissues, where proliferation and differentiation processes occur. Daughter cells are differentiated in the electric field excited by 12 mother and daughter cell pairs, turned out at cambial cell division. With aging, the cambial cell number is reduced to 7, close to thresholds level (6 cells), at which the differentiation of daughter cells is absent. The depression of cambial cell number with aging is connected with the work of another morphofunctional zone--the hypothalamus, which is the major center of vegetative regulation and initially has very high RhoA activity, which has been established in embryogenesis. Estrogens, influencing over the hypothalamus and activating Src kinase in its nuclei, reduce the level of RhoA activity, including SCN, responsible for many biorhythms of an organism. As a result, the hyperestrogenemia and therefore a connective tissue at first occur. Then there happens a hypoestrogenemia that leads to sharp falling of proliferative activity of cells, causing the depression of cambial cell number and possibility of a malignant tumor development. Along with this, there are the deep lesions of hormone regulation, leading to some lethal diseases. Thus, the RhoA increasing in hypothalamus and especially in SCN circadian rhythm can counteract the Src kinase intensifying and prevent the processes connected with this.
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PMID:[Participation of morphofunctional zones in aging processes]. 2373 4


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