Experimental study of the 4fn → 4fn and 4fn → 4fn-15d1 transitions of the lanthanide diiodides LnI2 (Ln=Nd, Sm, Eu, Dy, Tm, Yb).

The diffuse reflectance and photoluminescence (PL) spectra of NdI(2), SmI(2), EuI(2), DyI(2), TmI(2) and YbI(2) were measured between 225 and 12 500 nm in order to determine their 4f(n) â†’ 4f(n-1)5d(1) optical bandgaps. The results were compared with those obtained using an empirical model of the electronic structure of LnI(2). The results can be used to explain the lanthanide valency and crystalline structure changes of other lanthanide diiodides such as PrI(2).

Quetiapine in overdosage: a clinical and pharmacokinetic analysis of 14 cases.

Data on quetiapine overdosage are only sparsely available in the literature. This study provides additional data on the pharmacokinetics and clinical effects of intoxication with this atypical antipsychotic drug. The authors performed a retrospective analysis of all quetiapine intoxications reported to and screened by the toxicological laboratory of the Central Hospital Pharmacy The Hague between January 1999 and December 2003. Cases with known suggested amount of intake and medical outcome were included. From the patient's medical record and from the toxicological laboratory findings, patient demographic characteristics (gender, age), details of quetiapine intoxication (estimated time of ingestion, estimated amount of ingestion, and coingested drugs) and clinical parameters were obtained. Severity of intoxication was graded by the Poisoning Severity Score (PSS). Individual pharmacokinetic parameter values were calculated using a one-compartment open model and a Bayesian fitting procedure. Out of a total of 21 intoxications with quetiapine, 14 fulfilled the inclusion criteria. The ingested dose ranged from 1200 to 18,000 mg. The blood concentration ranged from 1.1 to 8.8 mg/L with a lag time of 1 to 26.2 hours between time of ingestion and blood sampling at the emergency ward. The most frequent findings were somnolence and tachycardia. The PSS was minor in 6 patients (43%), moderate in 5 patients (36%), and severe in 3 patients (21%). Severity of intoxication was not associated with a higher amount of quetiapine intake. The authors found no correlation between the serum concentration of quetiapine and the amount ingested. Elimination t(1/2) was not prolonged. It can be concluded that quetiapine intoxications appear to proceed mildly. Tachycardia and somnolence were the main clinical symptoms in our case series. No fatalities occurred. The severity of clinical symptoms was not associated with either a high serum concentration or the suggested amount ingested of quetiapine.

Facilitatory beta2-adrenoceptors on cholinergic and adrenergic nerve endings of the guinea pig trachea.

Using electrical field stimulation of epithelium-denuded intact guinea pig tracheal tube preparations, we studied the presence and role of prejunctional beta2-adrenoceptors by measuring evoked endogenous acetylcholine (ACh) and norepinephrine (NE) release directly. Analysis of ACh and NE was through two HPLC systems with electrochemical detection. Electrical field stimulation (150 mA, 0.8 ms, 16 Hz, 5 min, biphasic pulses) released 29.1 +/- 2.5 pmol ACh/g tissue and 70.2 +/- 6.2 pmol NE/g tissue. Preincubation for 15 min with the selective beta2-adrenoceptor agonist fenoterol (1 microM) increased both ACh and NE overflow to 178 +/- 28 (P < 0.01) and 165 +/- 12% (P < 0.01), respectively, of control values, increases that were abolished completely by the selective beta2-adrenoceptor antagonist ICI-118551 (1 microM). Further experiments with increasing fenoterol concentrations (0.1-100 microM) and different preincubation periods (1, 5, and 15 min) showed a strong and concentration-dependent facilitation of NE release, with maximum response levels decreasing (from nearly 5-fold to only 2.5-fold of control value) with increasing agonist contact time. In contrast, sensitivity of facilitatory beta2-adrenoceptors on cholinergic nerves to fenoterol gradually increased when the incubation period was prolonged; in addition, a bell-shaped concentration-response relationship was found at 15 min of preincubation. Fenoterol concentration-response relationships (15-min agonist preincubation) in the presence of atropine and yohimbine (1 microM each) were similar in the case of NE release, but in the case of ACh release, the bell shape was lost. The results indicate a differential capacity and response time profile of facilitatory prejunctional beta2-adrenoceptors on adrenergic and cholinergic nerve terminals in the guinea pig trachea and suggest that the receptors on adrenergic nerves are more susceptible to desensitization.

Improved extraction procedure for the assay of isosorbide-5-mononitrate in serum.

A procedure is described for the extraction of isosorbide-5-mononitrate from serum with diethyl ether-n-butyl acetate (15:1, v/v). After extraction, the diethyl ether is evaporated at room temperature and the nitrate remains dissolved in the relatively non-volatile n-butyl acetate phase. Glassware must be used throughout as the recovery of isosorbide-5-mononitrate is not reproducible when plastic tubes or plastic pipettes are used. The extraction recovery of isosorbide-5-mononitrate from serum is 67 +/- 7%, measured relative to external standards.

A novel, phospholipase C-independent pathway of inositol 1,4,5-trisphosphate formation in Dictyostelium and rat liver.

In an earlier study a mutant Dictyostelium cell-line (plc-) was constructed in which all phospholipase C activity was disrupted and nonfunctional, yet these cells had nearly normal Ins(1,4,5)P3 levels (Drayer, A.L., Van Der Kaay, J., Mayr, G.W, Van Haastert, P.J.M. (1990) EMBO J. 13, 1601-1609). We have now investigated if these cells have a phospholipase C-independent de novo pathway of Ins(1,4,5)P3 synthesis. We found that homogenates of plc- cells produce Ins(1,4,5)P3 from endogenous precursors. The enzyme activities that performed these reactions were located in the particulate cell fraction, whereas the endogenous substrate was soluble and could be degraded by phytase. We tested various potential inositol polyphosphate precursors and found that the most efficient were Ins(1,3,4,5,6)P5, Ins(1,3,4,5)P4, and Ins(1,4,5,6)P4. The utilization of Ins(1,3,4,5,6)P5, which can be formed independently of phospholipase C by direct phosphorylation of inositol (Stephens, L.R. and Irvine, R.F. (1990) Nature 346, 580-582), provides Dictyostelium with an alternative and novel pathway of de novo Ins(1,4,5)P3 synthesis. We further discovered that Ins(1,3,4,5,6)P5 was converted to Ins(1,4,5)P3 via both Ins(1,3,4,5)P4 and Ins(1,4,5,6)P4. In the absence of calcium no Ins(1,4,5)P3 formation could be observed; half-maximal activity was observed at low micromolar calcium concentrations. These reaction steps could also be performed by a single enzyme purified from rat liver, namely, the multiple inositol polyphosphate phosphatase. These data indicate that organisms as diverse as rat and Dictyostelium possess enzyme activities capable of synthesizing the second messengers Ins(1,4,5)P3 and Ins(1,3,4,5)P4 via a novel phospholipase C-independent pathway.

Pattern of 72-hour intragastric acidity in a homogeneous group of intensive care unit patients.

To gain insight into the variation over time of gastric acidity in postoperative ICU patients, intragastric pH was prospectively studied in patients undergoing elective abdominal aortic reconstructive surgery during a 72-hr intra- and postoperative period. Intragastric pH was monitored continuously in 14 patients with combined glass electrodes. During the day of surgery (day 1), the median 24-hr pH for all patients was 6.25 (5.8-7.0, IQR). However, three of the 14 studied patients had a median 24-hr pH of 1.8. The median 24-hr pH throughout day 2 for all was 2.45 (1.6-4.7, P = 0.001). The median 24-hr pH on day 3 was 1.6 (1.5-2.1, P = 0.001). Median 8-hr pH values demonstrate a remarkable interpatient and intraindividual variation in the course of the postoperative period. A progressive lowering of the intragastric pH was observed in the first 40 hr. From the 40- to 48-hr interval until the end of the study, no further significant decrease was found. The intragastric pH was above 4, 74% of the time during day 1, 39% during day 2 (P = 0.006) and 16% during day 3 (P = 0.003). Percentage of time above 4 on day 2 was significantly higher than on day 3 (P = 0.04). In conclusion, since gastric acid and pepsin seem to play a role in stress ulceration, this study suggests some patients are at risk of stress ulceration from the beginning of surgery, but most patients become at risk of stress ulceration in the course of the postoperative period.

Two potential Petunia hybrida mitochondrial DNA replication origins show structural and in vitro functional homology with the animal mitochondrial DNA heavy and light strand replication origins.

Four Petunia hybrida mitochondrial (mt) DNA fragments have been isolated, sequenced, localized on the physical map and analyzed for their ability to initiate specific DNA synthesis. When all four mtDNA fragments were tested as templates in an in vitro DNA synthesizing lysate system, developed from purified P. hybrida mitochondria, specific initiation of DNA synthesis could only be observed starting within two fragments, oriA and oriB. When DNA synthesis incubations were performed with DNA templates consisting of both the A and B origins in the same plasmid in complementary strands, DNA synthesis first initiates in the A-origin, proceeds in the direction of the B-origin after which replication is also initiated in the B-origin. Based on these observations, a replication model for the P. hybrida mitochondrial genome is presented.

The Reflotron Total Cholesterol assay in heparinized venous and capillary blood.

We recently evaluated the Reflotron Total Cholesterol dry chemistry assay by examining the calibration and the accuracy of the assay in serum, whole venous EDTA-blood and capillary EDTA blood. We now describe a study on the analysis in heparinized venous and heparinized finger stick blood. Cholesterol assays in venous serum and plasma, and in finger capillary blood and plasma (all with heparin) were compared. Finger capillary blood was obtained in two ways: 1. in heparinized capillaries; 2. in a Becton Dickinson microtainer that could be centrifuged for separation of the plasma. Venous blood was obtained in plain tubes (for serum) and heparinized tubes to obtain venous whole blood and also venous plasma. We did not, on average, find large differences between the concentrations of cholesterol in the various materials. The regression equations for finger capillary whole blood and venous whole blood however show higher slopes than the others. Inaccuracy due to the sampling technique appears to be no greater for finger capillary samples than for venous samples.

Demonstration of beta-casomorphin immunoreactive materials in in vitro digests of bovine milk and in small intestine contents after bovine milk ingestion in adult humans.

Healthy young volunteers ingested one liter of cows' milk; then the contents of the small intestine were aspirated through an intestinal tube at various times and assayed for the presence of bovine beta-casomorphin immunoreactive materials. Considerable amounts of beta-casomorphin-7, but no beta-casomorphin-5 and only small amounts of beta-casomorphin-4 or -6 immunoreactive materials were found. Chromatographical characterization showed that most of the beta-casomorphin-7 immunoreactive material was not identical with beta-casomorphin-7, whereas the major part of the beta-casomorphin-4 or -6 immunoreactive materials might be identical with their corresponding beta-casomorphins. Analogous results were obtained for in vitro digestion of bovine milk which had been designed as a rough imitation of the gastrointestinal digestion process. A regulatory influence of beta-casomorphins as "food hormones" on intestinal functions is suggested.

Isolation and physicochemical characterization of mitochondrial DNA from cultured cells ofPetunia hybrida.

Mitochondrial DNA ofPetunia hybrida was purified from cell suspension cultures. Up to 50% of the DNA could be isolated as supercoiled DNA molecules by CsCl-ethidium bromide density gradient centrifugation. The DNA purified from DNase-treated mitochondria bands at a single buoyant density of 1.760 gcm(-3) in neutral density gradients and runs on agarose gels as a single band with an apparent molecular weight exceeding 30 megadaltons (Md). Summing of the restriction endonuclease fragment lengths indicates a mitochondrial genome size of at least 190 Md. Electron microscopic analysis reveals the presence of a heterogeneous population of circular DNA molecules, up to 60 Md in size. Small circular DNA molecules, ranging in size from 2-30 Md are present, but unlike in cultured cells of other plant species they do not form discrete size classes and furthermore, they constitute less than 5% of the total DNA content of the mitochondria. The restriction endonuclease patterns of mitochondrial DNA do not qualitatively alter upon prolonged culture periods (up to at least two years).

Parental smoking. Its effects on fetus and child health.

Smoking is a risk factor in pregnancy. Maternal smoking reduces the birthweight by 150-250 g (dose-response relationship), shifting the birthweight (and length) distribution to the left. Reduction of birthweight without shortening of gestation creates a group of small-for-date babies. Intrauterine hypoxia seems responsible for the growth retardation in smokers' babies as in babies of mothers living at high altitudes. Cigarette smoking of the mother affects fetal oxygenation, due to high levels of COHb in the blood of both mother and child. This observation is strongly supported by animal experiments. The total of (abortions), stillbirths, early and late neonatal mortality (especially stillbirths) is higher in babies of smoking than in those of nonsmoking mothers and highest among the poor. Approximately 5% of all stillbirths and neonatal deaths must be attributed to the increased mortality risk for the infant of mothers who smoke during the second half of pregnancy. Pregnancies of smoking mothers show about the same increase in infant wastage as pregnancies at high altitudes. The babies of smoking mothers show little excess of congenital malformations, if any. The placenta coefficient is increased. This symptom of compensatory placental hypertrophy cannot avert some impairment of fetal nutrition. There is less preeclamptic toxemia in smokers than in nonsmokers, but a higher incidence of antepartum hemorrhage and placental separation. Concerning long-term effects, smoking during pregnancy seems to be associated with a slight impairment of mental and physical growth. When the mother is nonsmoker and the father smokes more than ten cigarettes daily, an increase in perinatal mortality seems probable. Smoke aggravates the asthma of children in about two-thirds of those whose parents smoke. Healthy children of smokers are sick more frequently (primarily respiratory illness) than those of nonsmokers. Smoking parents and teachers stimulate their children and pupils to start smoking. Once smokers children may remain smokers. From the polemics on cause (smoking) and association (smoker) regarding the effects of parental smoking on the health of the fetus, the conclusion must be that health workers involved in obstetrics have great responsibilities in the antismoking campaign.

Ischaemic heart disease in middle-aged men. Prevalence comparisons in Europe.

The authors report the results of a collaborative study of the prevalence of ischaemic heart disease in 6 samples of middle-aged male clerical workers, drawn from 5 European countries and covering in all 4522 subjects. Detailed standardization of data-collection methods and of coding, analysis and tabulation was undertaken.Estimated prevalence rates for angina and history of possible infarction, based on the use of a standard questionnaire, showed significant variation between samples, but the validity of international comparisons of symptoms remains unproven. Prevalence rates for ischaemic-type ECG findings were high everywhere, and mostly showed no significant variation between the groups studied. Central coding of ECG findings proved essential to the making of unbiased comparisons. Neither the prevalence rates for symptoms nor those for ECG findings in these samples were recognizably correlated with the corresponding national mortality rates for ischaemic heart disease.Several possible risk factors were studied, but the only one found to be consistently associated with ischaemic heart disease was a raised blood pressure. Cigarette smoking was strongly associated with bronchitic symptoms and dyspnoea, but an association with heart disease was not demonstrated.