Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prenatal cocaine (CC) exposure may result in increased fetal loss, growth retardation, altered neurodevelopment, and sudden infant death syndrome (SIDS). We sought to establish an animal model for prenatal cocaine exposure which (1) would allow us to distinguish the direct effects from the indirect and nutritional effects of the drug, and (2) might be used to address questions of cocaine's toxicity, specifically to the developing respiratory control system. The study design included 38 New Zealand White rabbit does among CC, pair-fed (PF), and free-fed (FF) groups. Miniosmotic pumps were implanted in each doe on day 10 of timed gestation providing continuous subcutaneous administration of either 30 mg/kg/day of cocaine HCl in H2O (CC) or sterile H2O alone (PF and FF). Mean (SEM) plasma cocaine concentration was 1.71 +/- 0.21 mumol/l (519.4 +/- 64.4 ng/ml). Pregnancy outcome compared for incidence of stillbirth, maternal death, spontaneous abortion, and gross malformation among 211 pups was significant only for increased stillbirths among CC pups (18%, p less than 0.04) as compared to PF (6%) and FF pups (7%). External and renal malformation and postnatal weight, crown-rump length, and snout-occiput head circumference for pups aged 4 and 5 days of age did not differ among groups. The direct effects of prenatal cocaine evaluated in our model do not reproduce the altered perinatal outcome observed among humans. However, our results do not determine if physiologic function has been altered. Investigation of the physiologic and pathologic abnormalities that are relevant to this human condition, specifically to the developing respiratory control system, should add clarity to the mechanism of action of cocaine during pregnancy.
 ...
PMID:Effects of prenatal cocaine exposure on perinatal morbidity and postnatal growth in the rabbit. 178 40

After unilateral uterine artery ligation in midpregnancy twelve guinea-pig does were anesthetized at 63 days of gestation. The ST waveform of the fetal electrocardiogram and the short term heart rate variability were studied during normoxia and in response to acute hypoxia in growth retarded fetuses (n = 12, mean +/- SEM, 58.5 +/- 3.9 g) and their normal sized littermates (n = 12, 94.3 +/- 3.5 g). Hypoxia was induced by letting the doe breathe a low-oxygen gas mixture. After 10 min of hypoxia fetal blood was sampled by decapitation and blood gases, acid-base status and catecholamine concentrations were analyzed. The does responded to decrease in inspired oxygen concentration with changes in oxygen tension (13.8 +/- 0.8 to 4.3 +/- 0.2 kPa) and oxygen saturation (99.9 +/- 0.1% to 70.5 +/- 1.8%). Fetal blood gases and plasma catecholamine concentrations did not differ between the groups. In the growth retarded group standard bicarbonate was significantly lower compared to controls. The T/QRS ratio (the quotient between T wave height and QRS peak to peak amplitude) was normal and similar in both groups prior to the hypoxic period. In response to hypoxia T/QRS ratio increased in the normal sized group and T/QRS was correlated to carbon dioxide tension, oxygen saturation, pH, lactate, standard bicarbonate concentration, standard base excess and plasma noradrenaline concentration, respectively. The growth retarded fetuses presented a completely different pattern where 7 out of 12 fetuses showed a biphasic ST waveform during hypoxia with depression and downward sloping of the ST segment and negative T wave.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:ECG waveform, short term heart rate variability and plasma catecholamine concentrations in response to hypoxia in intrauterine growth retarded guinea-pig fetuses. 194 Jan 43

Although the role of thyroid hormones in enhancing lung and brain maturation during the perinatal period is well established, the cellular mechanisms involved in these processes are incompletely understood. Hypothyroidism retards the development of fetal pulmonary insulin, neonatal pulmonary beta-adrenergic and neonatal brain insulin receptors. In this study, we investigated the effect of hypo- or hyperthyroidism on the development of neonatal brain and lung epidermal growth factor (EGF) receptors. The rabbit pups were rendered hypothyroid by adding 0.05% propylthiouracil to the drinking water starting at 23 days of gestation and thereafter. The neonatal hyperthyroid state was achieved by intramuscular administration of 100 micrograms/kg of synthroid to the rabbit doe on the 29th and 30th day of pregnancy. Neonatal plasma free thyroxine (T4) concentrations were quantitated by a radioimmunoassay. Brain and lung plasma membranes were isolated by differential centrifugation. EGF receptor characteristics were studied using 125I-EGF binding assays and Scatchard analysis. The plasma free T4 concentrations were 0.36 +/- (SEM) 0.02 (n = 6), p less than 0.01 (n = 7) and 1.76 +/- 0.1 (n = 6) ng/dl in the control, hypothyroid and hyperthyroid pups, respectively. The percent specific binding of 125I-EGF to 200 micrograms of brain plasma membrane (BPM) protein was significantly lower in the hypothyroid (0.62 +/- 0.03, n = 7, p less than 0.01), and higher in the thyroxine-treated (1.58 +/- 0.08, n = 6, p less than 0.01) group when compared to control (1.08 +/- 0.06, n = 6) animals. However, the percent specific binding of 125I-EGF to 100 micrograms of lung plasma membrane (LPM) protein was similar in all three groups (2.24 +/- 0.28, control; 2.01 +/- 0.5, hypothyroid, and 2.26 +/- 0.3, hyperthyroid). The number of EGF receptors per milligram of BPM protein (X 10(-10] were lower in the hypothyroid (2.24 +/- 0.03, n = 5) and higher in the hyperthyroid (6.6 +/- 0.02, n = 4) group when compared to control (4.4 +/- 0.05, n = 4) with no apparent difference in Kd. There was no difference in the number of EGF binding sites per milligram of LPM protein (X 10(-10] within the groups (6.6 +/- 0.8, n = 6, control; 7.9 +/- 0.4, n = 4, hypothyroid, and 7.3 +/- 0.3, n = 4, hyperthyroid). Presence of high affinity receptors for EGF in the neonatal brain as well as lung supports the hypothesis that EGF may play an important role in neonatal brain and lung maturation.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Thyroid-dependent maturation of neonatal brain but not lung epidermal growth factor receptors. 299 70

The presence of rabbit spermatozoa in the uterine horn of the doe over a 10-hr period induced an increase in the incorporation of leucine-14C and orotate-3H [from 230 +/- 50 to 520 +/- 32 and 146 +/- 41 to 432 +/- 40 (dpm 10(3) mg DNA; Mean +/- SEM)] into endometrial proteins and nucleic acids. The addition of actinomycin D or cyclohexamide significantly inhibited this process. The intraluminal administration of dibutyryl cyclic AMP (dbcAMP) (control group) induced an increase two times greater than that produced by spermatozoa. The increase in the incorporation of radioactive precursors into endometrial macromolecules induced by the spermatozoa is independent of the uterine carbonic anhydrase activation produced by this cell.
 ...
PMID:Effect of rabbit spermatozoa on the incorporation of labeled precursors into endometrial macromolecules. 616 Aug 22

Atenolol, a cardioselective beta-adrenergic blocking agent, was given as the sole hypotensive drug for 8-12 weeks to 20 patients with hypertension of varying degrees of severity. Initial systolic blood pressure ranged from 162-238 mm Hg (mean +/- SEM 196 +/- 5.5 mm Hg) and diastolic blood pressure ranged from 105-143 mm Hg (118 +/- 2.5 mm Hg). Three patients had accelerated hypertension, six had cardiomegaly with recent exertional dyspnea and three were diabetics. Atenolol, 100-300 mg once daily, controlled both the supine and standing blood pressure and markedly attenuated the initial hypertensive response to severe exercise. In 17 patients (85%), atenolol therapy reduced blood pressure more than 20/10 mm Hg; however, adequate blood pressure control was not achieved in severe hypertension. A significant hypotensive action developed within 2 weeks of treatment, and control of hypertension was maintained for 2 weeks after sudden interruption of therapy. No patient had postural or postexercise hypotension. The drug appeared to exert its maximum hypotensive effect at the 100-mg dosage. The magnitude of the hypotensive response was related to the initial systolic blood pressure (r = 0.77, p less than 0.01) and the degree of inhibition of exercise tachycardia (r = 0.66, p less than 0.01). The atenolol plasma level and its hypotensive action were not related. Except for impairment of glucose tolerance in diabetic patients, atenolol had minimal side effects.
 ...
PMID:Clinical evaluation of atenolol in hypertensive patients. 724 4

The mechanisms of exertional dyspnea relief in response to supplemental oxygen (O2) in chronic airflow limitation (CAL) are not precisely known and are likely multifactorial. To explore factors contributing to the relief of dyspnea after oxygen administration, 11 patients with severe CAL (FEV1.0 = 39 +/- 3% predicted, mean +/- SEM) and mild hypoxemia (resting PaO2 = 74 +/- 2 mm Hg) breathed room air (RA) and 60% O2 during exercise at approximately 50% of their maximal incremental exercise capacity. Breathlessness ratings (Borg scale), endurance time, respiratory drive (change in mouth occlusion pressure over the first 0.1 s of inspiration, P0.1), ventilation (VE), breathing pattern, operational lung volumes, gas exchange, and metabolic parameters were compared during RA and 60% O2. PaO2 at exercise cessation during RA and 60% O2 was 65 +/- 3 mm Hg and 226 +/- 12 mm Hg, respectively (p < 0.001). With 60% O2, the mean of individual Borg/time slopes fell significantly (p < 0.05) by 23 +/- 12% and was associated with a 35 +/- 11% increase (p < 0.01) in endurance time (r = -0.64, p < 0.05). During 60% O2, slopes of P0.1 and lactate over time also fell significantly (p < 0.05), whereas delta PaCO2/time did not change significantly. At a standardized time near end-exercise, Borg, VE, and P0.1 changed during 60% O2 by -0.8 +/- 0.3 (p < 0.05), -4.1 +/- 2.0 L/min (p = 0.07), and -1.3 +/- 0.5 cm H2O/s (p < 0.05), respectively. Slopes of Borg/VE, Borg/lactate, and VE/lactate were essentially superimposable during tests on RA and O2: Borg, lactate, and VE all fell proportionally during hyperoxia. In patients with CAL and mild exercise hypoxemia, relief of exertional breathlessness during hyperoxia is explained by reduced ventilatory demand in association with reduced blood lactate levels.
 ...
PMID:Factors contributing to relief of exertional breathlessness during hyperoxia in chronic airflow limitation. 903 90

We wished to determine which resting spirometric parameters best reflect improvements in exercise tolerance and exertional dyspnea in response to acute high-dose anticholinergic therapy in advanced COPD. We studied 29 patients with stable COPD (FEV(1) = 40 +/- 2% predicted [%pred]; mean +/- SEM) and moderate to severe chronic dyspnea. In a double-blind placebo-controlled cross-over study, patients performed spirometry and symptom-limited constant-load cycle exercise before and 1 h after receiving 500 micrograms of nebulized ipratropium bromide (IB) or saline placebo. There were no significant changes in spirometry, exercise endurance, or exertional dyspnea after receiving placebo. In response to IB (n = 58): FEV(1), FVC, and inspiratory capacity (IC) increased by 7 +/- 1%pred, 10 +/- 1%pred, and 14 +/- 2%pred, respectively (p < 0.001), with no change in the FEV(1)/FVC ratio. After receiving IB, exercise endurance time (Tlim) increased by 32 +/- 9% (p < 0.001) and slopes of Borg dyspnea ratings over time decreased by 11 +/- 6% (p < 0.05). Percent change (%Delta) in Tlim correlated best with DeltaIC%pred (p = 0.020) and change in inspiratory reserve volume (DeltaTLC%pred) (p = 0.014), but not with DeltaFVC%pred, DeltaPEFR%pred, or DeltaFEV(1)%pred. Change in Borg dyspnea ratings at isotime near end exercise also correlated with DeltaIC%pred (p = 0.04), but not with any other resting parameter. Changes in spirometric measurements are generally poor predictors of clinical improvement in response to bronchodilators in COPD. Of the available parameters, increased IC, which is an index of reduced resting lung hyperinflation, best reflected the improvements in exercise endurance and dyspnea after IB. IC should be used in conjunction with FEV(1) when evaluating therapeutic responses in COPD.
 ...
PMID:Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease. 1043 Jul 26

Bulk X-ray diffraction (XRD), synchrotron X-ray microdiffraction (microXRD), and scanning electron microscopy/ energy-dispersive X-ray spectroscopy (SEM/EDS) were used to characterize solids in residual sludge from single-shell underground waste tanks C-203 and C-204 at the U.S. Department of Energy's Hanford Site in southeastern Washington state. Cejkaite [Na4(UO2)(CO3)3] was the dominant crystalline phase in the C-203 and C-204 sludges. This is one of the few occurrences of cejkaite reported in the literature and may be the first documented occurrence of this phase in radioactive wastes from DOE sites. Characterization of residual solids from water leach and selective extraction tests indicates that cejkaite has a high solubility and a rapid rate of dissolution in water at ambient temperature and that these sludges may also contain poorly crystalline Na2U207 [or clarkeite Na[(UO2)O(OH)](H2O)0-1] as well as nitratine (soda niter, NaNO3), goethite [alpha-FeO(OH)], and maghemite (gamma-Fe2O3). Results of the SEM/EDS analyses indicate that the C-204 sludge also contains a solid that lacks crystalline form and is composed of Na, Al, P, O, and possibly C. Other identified solids include Fe oxides that often also contain Cr and Ni and occur as individual particles, coatings on particles, and botryoidal aggregates; a porous-looking material (or an aggregate of submicrometer particles) that typically contain Al, Cr, Fe, Na, Ni, Si, U, P, O, and C; Si oxide (probably quartz); and Na-Al silicate(s). The latter two solids probably represent minerals from the Hanford sediment, which were introduced into the tank during prior sampling campaigns or other tank operation activities. The surfaces of some Fe-oxide particles in residual solids from the water leach and selective extraction tests appear to have preferential dissolution cavities. If these Fe oxides contain contaminants of concern, then the release of these contaminants into infiltrating water would be limited by the dissolution rates of these Fe oxides, which in general have lowto very low solubilities and slow dissolution rates at near neutral to basic pH values under oxic conditions.
 ...
PMID:Residual waste from Hanford tanks 241-C-203 and 241-C-204. 1. Solids characterization. 1683 May 37

Environmental aerosolized particulates pose a potential risk to human health worldwide. Among others, high amounts of contaminants are generated especially in newly industrializing countries in the vicinity of industrial manufacturing, mining operations, but also during agricultural and natural processes. As an example of the needed multi-disciplinary diagnostic and differential diagnostic approach, we report a case of a 59-year old industrial worker who has suffered from chronic bronchitis and progressive dyspnea on exertion for 8years. He showed severe lung function impairment, a cavity in his right upper lung lobe, nodular and irregular opacities, fibrotic pleural changes and emphysema. According to the occupational history and the industrial hygiene report, he had been engaged in the production of various refractory materials and been exposed to very high levels of inorganic dust, especially to silica, silicon carbide and aluminum compounds, but also to carbon and other dusty materials for 28years. Histopathology of the two resected lung segments showed focally infarcted granulomas and chronic inflammation. Stains for organisms were negative. The lung tissue away from the granulomas showed significant dust deposition including dust macules. In spite of the inorganic dust deposits, with adjacent tissue lesions evident from the radiological findings (which were interpreted as atypical for pneumoconiosis) and the presence of granulomas in lung tissue, a diagnosis of necrotizing sarcoid granulomatosis was made, which was later changed to mixed-dust pneumoconiosis on further detailed examination. Scanning Electron Microscopy/Energy-Dispersive X-ray Spectroscopy (SEM/EDS) analysis of individual particles showed predominantly Si (silica or silicon carbide [SiC]) and Al particles (consistent with aluminum metal and/or oxide), as well as numerous Al silicates, Ti, and occasional Zr, Nb, V, steel, including Si fibers (consistent with SiC). We present the controversy about the pathogenesis of the lung disorder and whether it represents an occupational disease - which is more or less representative for many such cases.
 ...
PMID:Mixed-dust pneumoconiosis: Review of diagnostic and classification problems with presentation of a work-related case. 3036 72