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)

From June 1986 to December 1988, 107 patients (median age, 49 years; median performance score, 1) with haematogeneous metastases from breast carcinoma were treated with concomitant radiation and chemotherapy. Overall, 97% of the patients had been pretreated with surgery; 65%, with radiation; and 56%, with hormones. In all, 38% had received adjuvant chemotherapy. Patients with prior palliative chemotherapy were excluded from the study. All patients fulfilled at least two high-risk criteria. Chemotherapy was given according to the EI protocol (4-epirubicin and ifosfamide), and all patients simultaneously received radiation to the main tumour sites. Gastro-intestinal toxicity was moderate (11.1%, WHO grade 4), and bone marrow depression was marked in all cases. After three treatment courses, the overall response rate was 67% [21% complete response (CR), 46% partial response (PR)]. In all, 28% had stable disease (NC) and the rate of progressive disease (PD) was 5%. The median duration of tumour response was 8 months, with 12 months for CRs, 9 months for PRs and 6 months for NCs. The median survival was 13.5 months.
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PMID:Palliative chemo-radiotherapy with ifosfamide and epirubicin as first-line treatment for high-risk metastatic breast cancer. Results of a prospective multicenter trial. 169 17

This report investigates the hypothesis that gastro-oesophageal flow is modulated by central nervous activity. The hypothesis was examined using the canine model in which gastro-oesophageal flow was stimulated by gastric insufflation of air at 80 ml/min and central nervous depression was produced with the anaesthetic agents thiopentone, nitrous oxide and halothane. Duplicate paired studies were performed in four dogs, either unsedated or anaesthetized. Gastro-oesophageal flow was assessed manometrically by a sleeve catheter assembly and by pH electrode. Gastric compliance was assessed by inflation of a thin-walled, plastic bag. Transient lower oesophageal sphincter relaxation, the dominant mechanism of retrograde trans-sphincter flow in unsedated animals, was abolished by general anaesthesia. Retrograde flow of gas across the lower oesophageal sphincter in anaesthetized animals eventually occurred, but only after massive gastric distension and elevation of gastric pressure to lower oesophageal sphincter pressure. The effects observed could not be explained by a direct action of anaesthetic on the lower oesophageal sphincter or on the gastric wall. It is proposed that general anaesthesia results in blockade of the neural pathway responsible for transient lower oesophageal sphincter relaxation by withdrawal of facilitative higher centre activity. The findings have implications for the use of sedation in experimental studies on factors which control gastro-oesophageal reflux, and clinical application to the risk of tracheal aspiration during general anaesthesia.
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PMID:Effect of general anaesthesia on transient lower oesophageal sphincter relaxations in the dog. 325 Apr 18

The effect of histamine 2-antagonist famotidine on neuromuscular paralysis induced with either nondepolarizing or depolarizing neuromuscular blocking drugs was examined in anesthetized and mechanically ventilated rats. Neuromuscular paralysis, as judged by tibialis anterior muscle twitch tension in response to sciatic nerve stimulation, was maintained at about 50% with intravenous bolus and infusion regimens of either atracurium, gallamine, succinylcholine, or decamethonium. Famotidine, 0.1, 1, and 4 mg/kg, intravenously, were then administered at 5-min intervals as the infusion of the neuromuscular blocker was continued. Famotidine at any of these three doses failed to alter the steady state neuromuscular paralysis produced with either atracurium (prefamotidine versus final postfamotidine paralysis (mean +/- SE depression of twitch tension, n = 6, 49.8 +/- 2.8 vs 51.5 +/- 2.6%), gallamine (47.8 +/- 1.6 vs 47.6 +/- 3.0%), succinylcholine (49.2 +/- 1.8 vs 49.4 +/- 2.0%), or decamethonium (50.3 +/- 2.1 vs 51.5 +/- 2.0%). Intravenous famotidine at human therapeutic doses, fails to alter neuromuscular function in vivo in rats.
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PMID:Interaction between famotidine and neuromuscular blockers: an in vivo study in rats. 821 65

1. The CCKB/gastrin receptors mediating pentagastrin stimulation of gastric acid secretion by histamine release and by direct stimulation of oxyntic cells have been characterized in the immature rat isolated stomach assay. This was achieved by estimating antagonist affinity values for competitive antagonists from three distinct chemical classes (L-365,260, PD134,308 and JB93190) in the absence and presence of a high concentration of the histamine H2-receptor antagonist, famotidine (30 microM). 2. Pentagastrin produced concentration-dependent stimulation of gastric acid secretion in the absence and presence of famotidine. Famotidine depressed the maximum secretory response to pentagastrin although the degree of depression varied between experimental replicates (25-60%). This variation was attributed to the histamine-release mediated component of acid secretion, as judged by the consistency of the maximum responses obtained in the presence, but not absence, of famotidine. 3. All three CCKB/gastrin receptor antagonists behaved as surmountable antagonists in the absence and presence of famotidine. JB93190 (pKB approximately 9.1, approximately 8.9, in the absence and presence of famotidine, respectively) was approximately 30 fold more potent than either L-365,260 (pKB approximately 7.4, approximately 7.1) or PD134,308 (pKB approximately 7.6, approximately 7.4). 4. It was assumed that the famotidine treatment converted pentagastrin-stimulated acid secretion from a combination of an indirect action due to the release of histamine and a direct action on the oxyntic cell to solely a direct action on the oxyntic cell. A simple mathematical model of this two-receptor system was developed. The direct and indirect components were assumed to sum to produce the total response to pentagastrin obtained in the absence of famotidine. It was found that this model could account quantitatively for the behaviour of the three antagonists without invoking a difference in antagonist affinity for the CCKB/gastrin receptors mediating the direct and indirect actions of pentagastrin. However, a conclusion of receptor homogeneity has to be qualified because the model was also used to generate simulations which indicated that the analysis could only detect antagonist affinity differences of greater than one log-unit between enterochromaffin-like (ECL) and oxyntic cell CCKB/gastrin receptor populations.
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PMID:Pharmacological analysis of the CCKB/gastrin receptors mediating pentagastrin-stimulated gastric acid secretion in the isolated stomach of the immature rat. 896 49

The contractile response to histamine of tracheal muscle was studied in preparations from BSA-sensitized and non-sensitized guinea-pigs. Sensitization did not enhance the overall response to histamine. However, this response showed evidence of acetylcholine participation. In sensitized preparations, atropine (0.1 microM) caused a significant depression of the dose response to histamine (n = 11, p = 0.028), especially in the range 2-8 microM. Physostigmine (0.1 microM) significantly potentiated the effect of histamine (n = 8, p = 0.003), especially at greater than 4 microM histamine. The response to histamine of non-sensitized preparations was not altered by atropine (n = 11) or physostigmine (n = 8). The following agents did not discriminate between sensitized and non-sensitized preparations: Famotidine, an H2 antagonist; dimaprit, an H2 agonist; thioperamide, an H3 antagonist; alpha-methylhistamine, an H3 agonist; gallamine, an M2 antagonist, suggesting that muscarinic M2 receptor dysfunction alone is not sufficient to cause bronchial hyper-responsiveness. The results show that sensitization causes a change in the components of the contractile response to histamine rather than bronchial hyper-responsiveness to this agent.
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PMID:Histamine-evoked acetylcholine release in sensitized tracheal preparation. 923 91

Histamine H2 receptor-mediated responses were examined on cholecystokinin-octapeptide (CCK-8)-precontracted guinea pig gallbladder in vitro, testing histamine and a series of specific histamine H2 receptor agonists and antagonists. Among the antagonists tested, zolantidine and compound SKF 92857 were previously shown to antagonize H2 receptor-mediated responses in the heart, but not in the stomach. Histamine, in the presence of the H2 receptor antagonist mepyramine (10 microM), and the H2 receptor agonists dimaprit, impromidine and amthamine, inhibited CCK-8 (3 nM)-induced contractions in a concentration-dependent fashion, with the following rank orders of potency: impromidine > amthamine > histamine > dimaprit (pD2 values were 6.73 +/- 0.04, 5.44 +/- 0.07, 4.64 +/- 0.04 and 3.71 +/- 0.05, respectively). The maximal relaxation produced by dimaprit was significantly lower than that produced by histamine, as well as by impromidine and amthamine, which behaved as full agonists. All the H2 receptor antagonists examined were able to inhibit amthamine-induced relaxation. Famotidine (pA2 = 7.09 +/- 0.26), zolantidine (pA2 = 6.54 +/- 0.11), compound SKF 92857 (pA2 = 6.58 +/- 0.13) and aminopotentidine (pA2 = 6.86 +/- 0.06) competitively antagonised the amthamine-induced effect, while iodoaminopotentidine produced surmountable antagonism only at low concentrations (1 microM, pA2 = 6.83 +/- 0.21). Finally, the slowly-dissociable antagonist loxtidine caused a non-parallel displacement to the right of the concentration--response curve to amthamine (pKB = 7.55 +/- 0.24), with a significant depression of the maximal response to the agonist, even at the lowest effective concentration (0.3 microM). In conclusion, histamine H2 receptors in guinea pig gallbladder resemble those of the heart, as regards their sensitivity to zolantidine and compound SKF 92857, which, by contrast, were unable to antagonize histamine effects at gastric H2 receptors in different experimental models.
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PMID:Effects of histamine H2 receptor agonists and antagonists on the isolated guinea pig gallbladder. 1002 92

The themes of sex, gender, and women's health have been analyzed by various sciences. Medical and public health literature report on clinical aspects and epidemiology of risks affecting women, especially those of the reproductive process. The sexual division of labor means that the natural function of the woman is not considered economically productive in contrast to men. Women tend to be concentrated in lower grades of the remuneration scale, prestige, and autonomy, a phenomenon called the feminization of poverty. The construction of genders in the perspective of health means that being a man or a woman produces sexual differences in attitude and activities, which bring about specific risks for health and differentiation in the levels of access to health resources. On the macro level institutionalized sex differences manifest themselves in the high prevalence of malnutrition among girls in Latin America, the 2-3 times higher rate of depression among women, the high incidence of mortality among women from cancer, and the abuse of medical technology such as cesareans and hysterectomies. The Program of Integrated Assistance in Women's Health was conceived for the prevention and diagnosis of cervical uterine cancer, breast cancer, sexually transmitted diseases, and access to and choice of contraceptive methods.
Logos 1994
PMID:[Female sexuality as perceived by rural women]. 1228 48

Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.
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PMID:The Gut-Brain Axis, BDNF, NMDA and CNS Disorders. 2755 84