Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently several steroid compounds have been discovered to act as neuromodulators in diverse central nervous system (CNS) functions. We wondered if neuroactive steroids might be involved in affective illness or in the mode of action of mood-regulating medications such as carbamazepine. Levels of the neuroactive steroids pregnenolone and progesterone, as well as the neuropeptide diazepam binding inhibitor (DBI) (known to promote steroidogenesis), were analyzed from cerebrospinal fluid (CSF) obtained by lumbar puncture (LP) from 27 medication-free subjects with affective illness and 10 healthy volunteers. Mood-disordered subjects who were clinically depressed at the time of the LP had lower CSF pregnenolone (n = 9, 0.16 ng/ml) compared with euthymic volunteers (n = 10, 0.35 ng/ml; p < 0.01). In addition, pregnenolone was lower in all affectively ill subjects (n = 26, 0.21 ng/ml), regardless of mood state on the LP day, than healthy volunteers (p < 0.05). No differences were found for progesterone or DBI levels by mood state or diagnosis. Progesterone, pregnenolone, and DBI did not change significantly or consistently in affectively ill subjects after treatment with carbamazepine. CSF pregnenolone is decreased in subjects with affective illness, particularly during episodes of active depression. Further research into the role of neuroactive steroids in mood regulation is warranted.
 ...
PMID:CSF neuroactive steroids in affective disorders: pregnenolone, progesterone, and DBI. 804 7

This study demonstrates a significant impairment in the acquisition of conditioned avoidance responses in female rats during their estrus phase. Progesterone (PROG 5 mg) injected 6 h prior to the test, significantly enhanced the performance exhibited by rats at estrus, but not at diestrus. In ovariectomized rats, the acquisition of conditioned avoidance responses was similar to the exhibited during diestrus and this behavior was depressed by a single dose of estradiol benzoate (EB 2 micrograms) injected 48 h prior to the test. PROG antagonized the avoidance depression induced by EB, but it was not able to induce changes in the acquisition of conditioned avoidance response in ovariectomized rats without EB pretreatment. Estradiol appears to be the principal ovarian steroid modulating the acquisition of an avoidance task, whereas PROG seems to have a secondary role in this behavior, regulating the actions of estradiol on the brain. PROG failed to induce consistent changes in some spontaneous motor behaviors in intact and ovariectomized rats.
 ...
PMID:Progesterone effects on the acquisition of conditioned avoidance responses an other motoric behaviors in intact and ovariectomized rats. 804 42

The hemodynamic effects of propofol-fentanyl and isoflurane-fentanyl anesthesia during the prebypass period were compared in 42 patients undergoing coronary artery bypass grafting (CABG) and 22 patients undergoing valve replacement (VR) for stenotic lesions. Anesthesia was induced with fentanyl, 25 micrograms/kg, and pancuronium, 0.1 mg/kg, and was maintained with a propofol infusion commenced at 4 mg/kg/h (range 1 to 10 mg/kg/h) or with isoflurane commenced at 1% (range 0 to 2%). Additional fentanyl, 7.5 micrograms/kg, was given before sternotomy. Hemodynamic measurements were made before induction of anesthesia and at various times in the prebypass period. In the VR group, there were no significant differences between the two anesthetics in any hemodynamic variables during the study. Significant decreases (P < 0.05) in mean arterial pressure (MAP 14%), left ventricular stroke work index (LVSWI 29%), and stroke volume index (SVI 24%) occurred after 15 minutes of propofol anesthesia in the CABG group. With isoflurane MAP was well maintained with reductions in LVSWI and SVI of 22% and 20%, respectively. Isoflurane was, however, associated with a significant increase in heart rate (HR) in the CABG group (P < 0.05), whereas no significant change in HR occurred in CABG or VR patients receiving propofol. With both techniques there were no significant changes in right-sided or left-sided filling pressures or in systemic vascular resistance index in the CABG or VR groups, except for a decrease in pulmonary artery occlusion pressure in the propofol VR group and isoflurane CABG group at the time of aortic cannulation. Propofol produced similar hemodynamic changes in the CABG and VR groups. Both anesthetic techniques caused myocardial depression and effectively controlled the autonomic responses to sternotomy in both groups. The study suggests that propofol-fentanyl anesthesia is an acceptable technique for CABG surgery and for VR in patients with stenotic valvular heart disease.
 ...
PMID:Propofol-fentanyl anesthesia: a comparison with isoflurane-fentanyl anesthesia in coronary artery bypass grafting and valve replacement surgery. 806 Dec 62

Sex hormone, an essential hormone in reproduction, acts upon the tissues through binding to its receptors. Thus, the study on the receptors is essential for understanding the reproductive processes, physiologically or pathologically. With the advent of molecular biology, receptorology in our field has rapidly developed. In this lecture, we presented our recent findings on the receptor and its gene expression, together with some brief overview on the development of the receptor study, basically or clinically. I. Basic study. 1) Methology: A specific and highly sensitive quantitative RT-PCR assay for measurement of the steroid hormone receptor (SHR) mRNA was developed. 2) Rat progesterone receptor (PR) cDNA, especially PR-BcDNA, was partially cloned. Using primers designed upon the cloned cDNA, two distinct different promoters was found to exist in PR-A and B gene expression in the rat. 3) Tissue specificity of gene expression of the SHRs in the central and peripheral tissues: The synthesis of the receptor protein was regulated mostly on the level of transcription. In some tissues, however, the receptor synthesis was regulated posttranscriptionally. Gene expression of the SHRs was widely distributed even in non-target tissue, indicating the existence of 'basic action' of SH on the tissues. 4) Primate monkey studies: SHR, especially PR, was localized mostly in the preoptic hypothalamic region and hypophysis in contrast with its wide distribution in the rat brain, suggesting the more limited feedback site of progesterone in women. 5) Brain sex differentiation and acquisition of steroid sensitivity: Region-specific and dynamic appearance of SHRs during peri- and postnatal development seemed to a major determinant of sex differentiation and hormone sensitivity' acquisition in female rats. Based upon analysis of PR-A and B mRNAs, gene expression of PR-B was first 'turn on', followed by PR-B gene expression. Progesterone seemed to be associated with 'termination' of the critical period of sex differentiation in the brain. 6) Thyroid hormone may be a regulator of synthesis and gene expression of the PR in rat cerebral cortex. Arachidonic acid, released from cell membrane, regulated SHRs in a non-competitive way, indicating some 'second messenger' role. Cross-talk might exist between the membrane factor and SHR. 7) Antisense mRNA against GnRHmRNA, SH2RNA, was identified in rat brain. Most interestingly, there was a reciprocal relationship between GnRHmRNA and SH2RNA, suggesting some GnRHmRNA regulatory mechanism other than previously thought. 8) Depression of the GnRH receptor (GnRHR)mRNA level by GnRH agonist indicated another mechanism on down-regulation of GnRHR.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Basic and clinical studies on sex hormone receptors]. 808 3

Interactive effects between exogenous dopamine (DA) and isoflurane (I) combined with thoracic epidural blockade (TEA) were studied in dogs during chloralose anesthesia. The I-TEA intervention per se decreased heart rate (HR; 28%), mean arterial pressure (MAP; 63%), cardiac output (CO; 54%), left ventricular dP/dt (LVdP/dt; 75%) and LVdP/dt/systolic arterial pressure (SAP; 42%). Prior to the I-TEA intervention, dopamine increased MAP, CO, LVdP/dt, LVdP/dt/SAP and stroke volume (SV) already at the dose 10 micrograms.kg-1.min-1 and, additionally, increased mean pulmonary artery pressure (MPAP) at the dose 20 micrograms.kg-1.min-1. During the I-TEA intervention, the DA-induced increases in MAP and systemic vascular resistance (SVR) were significantly higher than prior to I-TEA, as indicated by significant ANOVA interactive effects. At the dose 10 micrograms.kg-1.min-1, DA restored MAP, CO, LVdP/dt, LVdP/dt/SAP and SV to levels found before the I-TEA intervention, while HR was restored first at the dose 20 micrograms.kg-1.min-1. At the dose 20 micrograms.kg-1.min-1, DA also increased MAP (39%), LVdP/dt (119%), LVdP/dt/SAP (73%), SVR (28%) and MPAP (70%) above levels prior to I-TEA. To conclude, exogenous dopamine effectively and dose-dependently counters cardiovascular depression induced by the anesthetic technique of combining I and TEA. The pressor and systemic vasoconstrictor actions of dopamine are potentiated by conjoint administration of I and TEA.
 ...
PMID:Cardiovascular depression by isoflurane and concomitant thoracic epidural anesthesia is reversed by dopamine. 817 48

Deletion of the SLT2 gene of Saccharomyces cerevisiae, which codes for a homologue of MAP (mitogen-activated) protein kinases, causes an autolytic lethal phenotype in cells grown at 37 degrees C. The gene encodes domains characteristic of protein kinases, which include a lysine (at position 54) that lies 19 residues from a glycine-rich cluster, considered to be the putative ATP binding site. The ability of three mutant alleles of SLT2 generated by site-directed mutagenesis, namely E54 (glutamic acid), R54 (arginine) and F54 (phenylalanine), to complement slt2 mutants was tested. All three failed to complement the autolytic phenotype and were unable to restore growth and viability of cells. A strain obtained by transplacement of slt2-F54 also behaved as a thermosensitive autolytic mutant. By immunoprecipitation with polyclonal antibodies raised against Slt2 protein expressed in Escherichia coli, it was possible to confirm that alteration of the lysine-54 residue did not affect the stability of the protein, thus allowing us to conclude that activity of the Slt2 protein kinase is critically required for growth and morphogenesis of S. cerevisiae at 37 degrees C. A significant fraction of the mutant cell population lysed at 24 degrees C and the cells displayed a characteristic alteration of the surface consisting of a typical depression in an area of the cell wall. At 37 degrees C, the cell surface was clearly disorganized.
 ...
PMID:Activity of the yeast MAP kinase homologue Slt2 is critically required for cell integrity at 37 degrees C. 823 2

A study was made of all women who had been inpatients of the mental health or disability units of Porirua Hospital in New Zealand for at least 6 months who were prescribed oral or injectable hormonal contraceptives during January 1992. The aim was to describe the use of hormonal contraceptives in this population and assess the appropriateness and safety of this method as well as the patient consent process and patient satisfaction. Data were collected from medical records and from interviews with the patients (when possible) and their nurses. 42 women were prescribed contraceptives (60% of those under 50). 3 were married, 3 separated or divorced, and 36 never married. 32 were nulliparous, none had more than 2 children. 11 were Maoir, 1 Pacific Islander, and 29 New Zealand pakeha. 23 women were intellectually disabled, 28 had mental disorders, 9 had both. 29 of the women received Depo Provera, 7 progesterone-only oral contraceptives (OCs), and 6 combined OCs. 25 had been using their current contraceptive for more than 3 years. Treatment was prescribed by psychiatric staff in 16 cases, other staff in 25, and outside practitioners in 1. The reason for treatment was contraception in 32 women and menstruation prevention in 9. 27 women were smokers (21 heavy). 7, including 6 of the heavy smokers, had other contraindications to the use of estrogens. Of the 26 women interviewed, 12 complained of side effects, 8 of weight gain, 2 of depression, and 5 of other effects (the nurses identified only 2 of 42 women as suffering side effects). Of the 22 interviewees who were treated for contraception, 15 stated they were sexually active. The nurses thought that 29 of the 42 were or might be sexually active. Therefore, 13 women considered definitely not sexually active were prescribed contraceptives. Very few of the women used condoms, although 38% knew how to practice safe sex. 14 of the women interviewed stated they chose contraception. The nurses said 8 had given consent, the families of 2 gave consent, consent information was unknown for 10, and a unilateral staff decision was made for 22. 17 of the 28 women definitely treated without consent were mentally retarded. The women were given very little information about their contraceptive method and knew of very few other methods. These results indicate that contraceptives have been used to manage menstrual hygiene and address staff concerns. In some cases, their administration without consent was illegal. The patients received inadequate medical care and some of the prescriptions were inappropriate. Ethically correct ways in which to address the problem of contraception in this population exist through educationally-focused family planning services for both in- and out-patients.
 ...
PMID:Use of hormonal contraceptives in an institutional setting: reasons for use, consent and safety in women with psychiatric and intellectual disabilities. 834 76

Experimental arthritis and inflammation have been reported to reduce liver cytochrome P-450-dependent mono-oxygenase activities with subsequent impairment of drug metabolism. Interleukin-1 beta (IL-1) is among the proven mediators of both inflammation and P-450 decrease, although some paradoxical effects were sometimes reported in experimental models of arthritis. The aim of the present study was to evaluate the main liver drug-metabolizing isoenzymes during established collagen-induced arthritis in rats, and to investigate whether a systemic IL-1 treatment was able to mimic or sometimes to reverse the influence of the inflammatory process on these enzymes. Arthritis was induced on day 0 by type II collagen and a low dose (0.2 mg) of N-acetylmuramyl-L-alanyl-D-isoglutamine, and human recombinant IL-1 was administered s.c. at the daily dose of 0.02, 0.2 or 2.0 micrograms per arthritic rat, from day 21 to 25 and on day 28. Ethoxyresorufin-O-deethylation was depressed 6-fold in arthritic rat liver microsomes and the highest dosage of IL-1 potentiated this depression. Pentoxyresorufin-O-deethylation decreased by 50% in arthritic rat, a dose-dependent decrease being observed after IL-1 treatment. Progesterone 6 beta-hydroxylation and P-450 IIIA protein increased by 2-fold in both untreated arthritic rat liver microsomes and those treated by the lowest dose of IL-1. The two higher doses decreased this activity, vs. the dose, to reach the naive level. Lauric acid hydroxylation increased 2-fold in arthritic rat and was further potentiated by IL-1. UDP glucuronosyl transferase IA2 activity was increased 2-fold in arthritic rats, with subsequent decrease after 2.0 micrograms of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interleukin-1 beta differentially represses drug-metabolizing enzymes in arthritic female rats. 843 2

The US Food and Drug Administration finally approved the injectable contraceptive Depo-Provera (DMPA) in October 1992, 25 years after its introduction. Women return to a health facility every 90 days for an intramuscular injection of 150 mg DMPA, which provides them 99% effective contraception. Menstrual changes and spotting are the leading reasons for DMPA discontinuation. Eventually, more than 50% of DMPA users develop amenorrhea. During the first year, women gain about 2 kg and weight increases as time passes. Weight gain is the second leading reason for DMPA discontinuation. DMPA may adversely affect glucose tolerance in women at risk for diabetes, but it does not affect cardiovascular or metabolic functions. It may increase the risk of osteoporosis. A rare side effect is convulsions. 1-10% of DMPA users have other central nervous system effects, such as headaches, dizziness, and depression. Itching and rashes may develop. Fertility returns within 1 year after discontinuation. DMPA is linked to low birth weight. It apparently does not harm breast-fed infants or hinder lactation. A World Health Organization study shows that DMPA users less than 35 years old experience a slight increase in breast cancer but a reduced incidence of endometrial cancer. Nurses are instrumental in guiding women as they choose DMPA and in informing them about its potential side effects, including breast cancer risk. They must screen women for pregnancy and evaluate their risk of breast cancer. They must determine whether women are able to return every 3 months for DMPA injections. Women who select DMPA must use other contraception, e.g., barrier protection, within the first 24 hours after initial injection. Nurses should counsel them about the likely menstrual changes to reduce the likelihood of dissatisfaction. They should recommend a daily dose of 1200 mg of elemental calcium and daily exercise of long bones to minimize the risk of developing osteoporosis.
 ...
PMID:Depo-Provera. 849 47

The goal of therapy in patients with severe head injury is to avoid secondary brain damage. Analgesia and sedation are an essential part of the therapy, and several drugs are in current use. However, few controlled clinical trials have been performed so far, and none of these drugs has proved to be superior. Although in the past the therapy has been focused on controlling elevated intracranial pressure (ICP), many authors emphasize the role of cerebral ischaemia in the prognosis of patients. Therefore, cerebral perfusion pressure (CPP) i.e. the difference between ICP and mean arterial pressure (CPP = MAP-ICP), seems to be more important than ICP alone. Analgesics and sedatives reduce the cerebral metabolic rate (CMR), and the consequent decrease in cerebral oxygen uptake might prevent ischaemic damage in regions with low perfusion. Moreover, a decrease in CMR is often associated with a decrease of cerebral blood flow (CBF) in regions with normal perfusion and, as a result, ICP is also reduced. Basically, the cerebral effects (on ICP, CMR, and CBF) and the haemodynamic effects with respect to maintenance of a sufficient CPP are most important in the selection of drugs for analgosedation. In addition, the effects on general intensive care management must be considered (pulmonary function, immunreactivity bowel motility). The purpose of this paper is to describe drugs commonly used for analgosedation in severe head injury. Barbiturates bring about the most pronounced decrease of CMR and ICP. In the past these drugs were used routinely in high doses ("barbiturate coma"). However, no improvement in outcome was demonstrable, and vitally dangerous side effects, such as infection, pulmonary dysfunction, arterial hypotension, and renal failure often occurred. High-dose barbiturate therapy is therefore only indicated in exceptional cases, such as refractory increase in ICP with preserved CO2 response of cerebral vessels. The effect is dependent on CMR at the start of this therapy. Benzodiazepines are frequently used in patients with head injury. They cause only a moderate decrease of CMR and ICP. In general, side effects are negligible. However, a possible decrease of MAP by reduced central sympathetic drive has to be taken into account. Opioids are also frequently used in patients with head trauma. The observed cerebral effects are inconsistent. Some authors have described increases in ICP, CBF, and CMR, but in most studies no influence on these values, or a decrease, has been observed. In any case, cautious titration of these drugs and cerebral monitoring are therefore desirable. As with benzodiazepines, a decrease in MAP due to central effects is possible. In addition, opioids inhibit bowel motility. Ketamine is generally used because of its favourable circulatory effects, bronchodilatation and absence of inhibition of bowel motility. In patients with increased ICP, however, it is often considered contraindicated, since it can be associated with cerebral vasodilation and ICP increase. Other studies did not confirm an increase of ICP when controlled ventilation and additional sedation were applied. More recent studies have demonstrated the role of neuroexcitatory NMDA-receptors in ischaemic and traumatic brain damage. Since ketamine exerts an antagonistic effect on N-methyl-D-aspartate receptors (NMDA) and studies in animals have demonstrated a protective effect of ketamine against ischaemic and traumatic brain damage, controlled clinical studies in patients with head injury are desirable. Propofol results in a profound decrease of CMR and a significant decrease of ICP, but often also in haemodynamic depression. Few results obtained during long-term administration are available, but it seems to be beneficial. More clinical studies are warranted. Gamma-hydroxybutyrate (GHB) is a physiological substance, which has only sporadically been investigated for sedation in patients with head trauma. The few available studies show beneficial res
 ...
PMID:[Analgesia and sedation in patients with head-brain trauma]. 859 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>