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 retention of degradation of insulin by isolated perfused liver have been examined. Noncyclically perfused livers from streptozotocin-diabetic rats retained 25% and degraded 10% of 125I-insulin administered as a 1-min pulse. On gel filtration (Sephadex G50F), the degradation products released into the vascular effluent eluted in the salt peak. During the 45-min interval after the end of the 125I-insulin infusion, 0.19% of the total dose was excreted in the bile. 60-90% of this material consisted of iodinated, low-molecular-weight degradation products. Inclusion of native insulin with the 125I-insulin in the pulse depressed both the retention and degradation of iodinated material; however, this reflected increased retention and degradation of the total insulin dose (125I-insulin plus native hormone). The log of the total amounts of insulin retained and degraded were linearly related to the log of the total amount of insulin infused at concentrations between 12.7 nM and 2.84 muM. Increasing the amount of native insulin in the infused pulse also depressed the total amount of iodinated material found in the bile and led to the appearance in the bile of intermediate-sized degradation products that did not simultaneously appear in the vascular effluent. Addition of high concentrations of glucagon to the infused 125I-insulin had no effect on the retention or degradation of the labeled hormone, or on the apparent size and amount of iodinated degradation products found in the vascular effluent or in the bile. Preinfusion of concanavalin A inhibited both 125I-insulin retention and degradation. A greater depression by concanavalin A of degradation than binding was also observed with isolated hepatocytes. In contrast to 125I-insulin, the retention and degradation of two iodinated insulin analogues of relative low biological potency, proinsulin and desalanyl-desasparaginyl insulin, were small. The amount of radioactivity appearing in the bile after infusion of these analogues was almost negligible. However, degradation products of these analogues that appeared in the bile and in the vascular effluent was qualitatively similar to those found after the infusion of 125I-insulin. Our findings suggest that the rapid initial uptake of 125I-insulin after its infusion into noncyclically perfused liver, as well as its subsequent degradation, behaves in a qualitatively similar fashion to the binding of 125I-insulin and its degradation by isolated rat hepatocytes. This uptake and the subsequent phase of degradation may be attributable to binding of insulin at specific recognition sites, preliminary to its transfer to a degradative site(s) presumed to be located inside the cell.
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PMID:Retention and degradation of 125I-insulin by perfused livers from diabetic rats. 13 20

12 metabolically healthy subjects were i.v. administered equipotent doses (ED30) of tolbutamide (7.5 mg/kg), glisoxepide (0.02 mg/kg) and glibenclamide (0.006 mg/kg). Prior to and 2, 5, 8, 10, 20, 40, 60 and 120 min after the injection the following serum parameters were determined: blood glucose, immunologically measurable insulin (IMI) with the double-antibody method (Hales and Randle) and proinsulin (IMP) enzymatically (ISP-method). The maximum level of insulin follows the injection of tolbutamide with a value of 70.5 micronU/ml after 2 min, of glisoxepide after 5 min (67.0 micronU/ml) and of glibenclamide after 20 min (32.3 micronU/ml). The proinsulin fraction of the total insulin shows a level of 12.5 micronU/ml before the test. After the administration of the three compounds proinsulin increases, too, but reaches only 20-40% of the total immunoreactive insulin. The amount of secreted insulin and proinsulin during the 120-min test is rather the same for the three substances. The average increase of insulin is nearly identical for tolbutamide and glisoxepide, whereas it is less for glibenclamide. Both the mean blood sugar depression and the highest mean increase of proinsulin is reached after glisoxepide. The significance of the one-chain precursor of insulin as a part of the sulfonylurea stimulated total insulin for glucose depression is discussed.
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PMID:[Insulin and pro-insulin secretion following intravenous administration of tolbutamide, glisoxepide and glibenclamide]. 41 45

Concentrations of immunoreactive insulin activity (IRI) and proinsulin activity (IRP), blood glucose, free fatty acids (FFA), glycerol, cholesterol, triglycerides were analyzed in 140 subjects suspect of protodiabetes and 50 healthy persons before, during and after a glucose infusion test (GIT). The protodiabetic subjects were classified into normweight, overweight, obese, hyperlipemic groups with diet or with Regadrin therapy and each of them subdivided into such with normal and such with pathological carbohydrate tolerance. Norm- and overweight subjects with asymptomatic diabetes were characterized by a significant reduction of insulin secretion during both phases. Obese patients with or without hyperlipoproteinemia demonstrated an increased IRI reaction during the late phase of secretion. Carbohydrate intolerance was associated with an enhancement of basal triglyceride levels and a reduced depression of glycerol and FFA during the GIT. There were no differences in fasting or reactive IRP concentrations between healthy and protodiabetic subjects with normal carbohydrate tolerance. In asymptomatic diabetes the IRP levels were increased during the late secretion phase, but the percentage of IRP in total IRI was normal or--in existing high response--significantly reduced in comparison to norm response. The results do not support an enhanced IRP secretion as the cause of carbohydrate intolerance.
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PMID:Effect of glucose infusion on venous blood levels of immunoreactive proinsulin activity, insulin activity and fat parameters in healthy and protodiabetic subjects. 122 47

A quantitative analysis of the molecular weight (MW) profile of urinary protein by SDS-PAGE was performed in streptozotocin (STZ)-injected, non-ketotic diabetic rats (DM group), diabetic rats receiving dipyridamole (DM-DIP group), normal rats (C group) and STZ-injected rats with near-normal glycemia due to insulin treatment (DM-INSULIN group). In the DM group, decrease of a small MW protein (SMWP) (MW 19.5 k) was found at 2.5 weeks, and an increase of larger MW proteins (LMWP) (MW 68 [albumin], 55 and 29 k) together with a decrease of SMWPs (MW 19.5 and 15 k) was found at 15 weeks, as compared to the C group: the MW profile of urinary protein in the DM-INSULIN and C groups was indistinguishable. At 15 weeks, creatinine clearance (Ccr) was significantly depressed and an increase in the mesangial matrix with electron dense deposits was evident in the DM group. The urinary protein abnormalities were partially corrected and the reduction of Ccr was absent in the DM-DIP group with no effect on glomerular morphology. STZ-induced diabetes in rats is accompanied by a reduction of urinary SMWP, and a subsequent increase of LMWP and depression of Ccr: dipyridamole ameliorates urinary protein abnormalities and prevents the reduction of Ccr.
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PMID:Abnormal molecular weight profile of urinary protein in rats with streptozotocin-induced diabetes. 144 72

There are increasing numbers of reports on the tobacco smoking and ingestion of abused drugs (e.g. morphine, cocaine) by pregnant women and the effects of the substances on the developing fetus and newborn infant. The passage of drugs and chemicals from the mother to the fetus is influenced by the placental transport and metabolism of the substances. Further, these drugs and chemicals affect the nutrient transport systems in the placenta. The three major drugs of abuse-nicotine, morphine and cocaine-depress both active amino-acid uptake by human placental villi and transplacental amino-acid transport by reason of the drugs' influence on placental cholinergic and opiate systems. Part of this depression (10-16%) is not reversible. Nicotine blocks the cholinergic receptor and thus blocks acetylcholine (ACh)-facilitated amino-acid transport. Morphine stimulates opiate kappa receptors and depresses ACh release. Cocaine blocks Ca2+ influx and thus blocks ACh release. ACh causes dilation of blood vessels and maintains placental blood flow by the activation of endothelial muscarinic receptors. By interfering with ACh release and placental blood flow, the three drugs of abuse may depress the diffusion of amino acids and other nutrients from the trophoblast into the placental circulation. Three regulatory systems are delineated for amino-acid uptake by the placenta: placental ACh, phospholipid N-methyltransferase, and the gammaglutamyl cycle. These systems operate in concert with one another and are dependent on cellular formation of adenosine 5'-triphosphate (ATP). Placental hypoxia induced by carbon monoxide and other tobacco gases depresses the energy-dependent processes and thus the ATP levels of placental cells. Maternal tobacco smoking and drug abuse cause placental insufficiencies for amino-acid transport, which may partially explain the fetal intrauterine growth retardation caused by these substances. Part of the amino-acid deficits may be compensated for by the induction of new amino-acid transport systems. Specific receptors or drug-binding proteins for the three drugs of abuse are present in the placenta. A DNA adduct selective for maternal smoking has been demonstrated in the placenta. DNA adducts selective for cocaine, morphine and other environmental chemicals have yet to be demonstrated ins the placenta.
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PMID:Placental toxicology: tobacco smoke, abused drugs, multiple chemical interactions, and placental function. 195 23

This study was to evaluate the dynamic changes in cardiac autonomic control preceding electrocardiographic (ECG) myocardial ischemia in patients with syndrome X. Twenty-four-hour ambulatory ECG was obtained in 34 consecutive patients in a drug-free state. Fourteen (41%) of them, aged 58.8+/-13.5 years, presented a total of 19 ischemic episodes, mean duration 12.4+/-19.8 min (ranged 1 to 90 min). Heart rate variability was measured for 24 h; for 3 min and 30 min before, and during the 15 min (in five 3-min intervals) immediately antedating ST segment depression; and for another 3 min after ST segment back to normal. There were significant progressive shortenings in sinus cycle lengths over the 30 min preceding myocardial ischemia (-30 vs -3 minute, 822+/-32 ms vs 637+/-23 ins, P<0.05; a decrement of 22.5%). The sinus cycle lengths lengthened after ischemia ceased. High frequency activity, pNNSO and rMSS.D. were significantly reduced from the -30 min baseline to a nidus in the last 3 min before ischemia (P<0.05), whereas low frequency band and low/high frequency ratio did not present significant change. These findings strongly argue that cardiac autonomic control, especially vagal withdrawal, is involved in the pathogenesis of dynamic myocardial ischemia in syndrome X.
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PMID:Parasympathetic withdrawal antedates dynamic myocardial ischemia in patients with syndrome X. 987 77

We examined the influence of two K(ATP) channel openers, diazoxide and an analog (NNC 55-0118), on experimental beta-cell damage induced by streptozotocin (STZ; 0.5 mmol/l). Rat pancreatic islets were exposed to diazoxide or NNC 55-0118 for 30 min and were further incubated for 30 min after the addition of STZ. The islets were then washed and cultured for 24 h. Islets exposed to STZ alone showed extensive morphological damage, reduced glucose oxidation, low insulin content, and severely impaired glucose-stimulated insulin secretion and proinsulin biosynthesis. Islets treated with STZ in the presence of the channel openers (0.03-0.30 mmol/l) showed dose-dependent preservation of the morphology and improved glucose oxidation rates, insulin content, and secretion. NNC 55-0118 was capable of fully counteracting the STZ impairment, whereas diazoxide had a less protective effect. NNC 55-0118 did not counteract STZ-induced depression of islet NAD levels when examined 2 h after STZ exposure, which suggests that the mechanism of action by NNC 55-0118 is not through an inhibition of poly(ADP-ribose) polymerase. The results illustrate that K(ATP) channel openers can protect insulin-producing cells against toxic damage, an effect that may be of use in subjects with ongoing insulitis.
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PMID:K(ATP) channel openers protect rat islets against the toxic effect of streptozotocin. 1090 69

Prospective studies ware carried in 200 lying-ins. To diagnose affective disorders medical interview and anonymous questionnaire BDI and EPDS were used. During interview 31% showed baby-blues. Signs of postpartum depression occurred in 18.5% women. No case of psychosis as well as critical incident of stress debriefing were stated. Recapitulating postpartum affective disorders occurred in 49.5% of examined group. Among negative psycho-socioeconomic factors pathological course of pregnancy in 14%, incorrect relationship with parents in 9%, low material status in 7%, unemployment in 32% and unwanted pregnancy in 3% of women were observed. Affective disorders in lying-ins women with postpartum depression are correlated with occurring of least 3 of above-mentioned factors. Baby-blues was found in 31%, while signs of depression were found in 17-20% of women during first week of puerperium. Existence of at least 3 negative psycho-socioeconomic factors during pregnancy or labour correlates with appearance of postpartum depression.
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PMID:[Characteristic of affective disorders of the first week of puerperium]. 1466 17

Metachromatic leukodystrophy (MLD) is a metabolic disease that has recently been investigated as a model for the study of psychosis. We report on two sisters with adult-type MLD who developed psychiatric symptomatology, but differed in their expression of psychotic and depressive symptoms. Association studies have indicated that polymorphisms in genes encoding the serotonin and dopamine transporters and receptors are related to the symptomatology of schizophrenia and/or depression; hence both sisters were genotyped for some of these candidate genes. The sisters shared dopamine receptor D(2) (DRD(2)) c.1047GG (p.311Ser/Ser) and c.-141Cins/ins polymorphisms, which are significantly associated with schizophrenia, but differed in the serotonin transporter gene-linked polymorphic region and serotonin receptor 1A (5-HT(1A)) c.-1019C to G polymorphisms, which may have increased the elder sister's susceptibility to depressive symptoms. Much bigger samples would be needed to gain enough statistical power to develop any hypotheses. This is the first report on genotyping MLD patients for candidate genes for psychiatric disorders, although MLD has been proposed as a model for schizophrenia.
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PMID:Polymorphisms in genes encoding the serotonin and dopamine pathways in two sisters with metachromatic leukodystrophy. 1883 10

The purpose of this study was to examine the efficacy of the Youth-Nominated Support Team-Version II (YST-II) for suicidal adolescents, an intervention based on social support and health behavior models, which was designed to supplement standard treatments. Psychiatrically hospitalized and suicidal adolescents, 13-17 years of age, were randomly assigned to treatment-as-usual (TAU) + YST-II (n = 223) or TAU only (n = 225). YST-II provided tailored psychoeducation to youth-nominated adults in addition to weekly check-ins for 3 months following hospitalization. In turn, these adults had regular supportive contact with adolescents. Adolescents assigned to TAU + YST-II had an average of 3.43 (SD = 0.83) nominated adults. Measures included the Suicidal Ideation Questionnaire-Junior (SIQ-JR; W. M. Reynolds, 1988), Children's Depression Rating Scale-Revised (E. O. Poznanski & H. B. Mokros, 1996), Beck Hopelessness Scale (A. T. Beck & R. A. Steer, 1993), and Child and Adolescent Functional Assessment Scale (CAFAS; K. Hodges, 1996). YST-II had very limited positive effects, which were moderated by history of multiple suicide attempts, and no negative effects. It resulted in more rapid decreases in suicidal ideation (SIQ-JR) for multiple suicide attempters during the initial 6 weeks after hospitalization (small-to-moderate effect size). For nonmultiple attempters, it was associated with greater declines in functional impairment (CAFAS) at 3 and 12 months (small effect sizes). YST-II had no effects on suicide attempts and no enduring effects on SIQ-JR scores.
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PMID:The Youth-Nominated Support Team-Version II for suicidal adolescents: A randomized controlled intervention trial. 1980 68


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