Synthesis and antiallergic activity of pyridothienopyrimidines

The synthesis of a series of pyridothienopyrimidines and their evaluation as inhibitors or inducers of the release of histamine from rat mast cells is reported. The activity was measured after immunological stimulation with ovoalbumin and chemical stimulation with polymer 48/80 and the drugs adryamicin and vinorelbine. The experiments were carried out with and without preincubation of the stimulus with the cells before addition of the drug. Several pyridothienopyrimidines show inhibitory IC50 values in the range 2-25 microM, indicating they are up to 100 times more potent than cromoglycate (DSCG) and 10 times greater than Ketotifen. Compound 9l is a potent inhibitor in all the conditions tested and shows IC50 = 9-25 microM. Pyridothienopyrimidines 4l and 9e are very strong inducers of histamine release in the immunological (4l, 170-230%) and chemical (9e, 100-150%) assays, respectively. Compounds 4l and 9i are cytotoxic in vitro (IC50 = 0.1-0.2 microgram/mL) against P-388, A-549, HT-29, and MEL-28 tumor cell lines.     

Abortion surveillance--United States, 1995

CONDITION: Since 1990 (i.e., the year in which the number of abortions was highest), the annual number of abortions in the United States has decreased by 15%. REPORTING PERIOD COVERED: This report summarizes and reviews information reported to CDC regarding legal induced abortions obtained in the United States during 1995. DESCRIPTION OF SYSTEM: For each year since 1969, CDC has compiled abortion data received from 52 reporting areas: 50 states, the District of Columbia, and New York City. RESULTS: In 1995, a total of 1,210,883 legal abortions were reported to CDC, representing a 4.5% decrease from the number reported for 1994. The abortion ratio was 311 legal induced abortions per 1,000 live births, and the abortion rate was 20 per 1,000 women aged 15-44 years, the lowest ratio and rate recorded since 1975. Women who were undergoing an abortion were more likely to be young, white, and unmarried; most were obtaining an abortion for the first time. Approximately half of all abortions (54%) were performed at < or =8 weeks of gestation, and approximately 88% were performed before 13 weeks. Approximately 16% of abortions were performed at the earliest weeks of gestation (< or =6 weeks), approximately 17% at 7 weeks of gestation, and approximately 21% at 8 weeks of gestation. Few abortions were provided after 15 weeks of gestation -- approximately 4% of abortions were obtained at 16-20 weeks, and 1.4% were obtained at > or =21 weeks. Younger women (i.e., women aged < or =24 years) were more likely to obtain abortions later in pregnancy than were older women. INTERPRETATION: Since 1990, the number of abortions has declined each year. Since 1987, the abortion-to-live-birth ratio has declined; in 1995, it was the lowest recorded since 1975. This decrease in the abortion ratio reflects a trend that a lower proportion of pregnant women obtain induced abortion. ACTIONS TAKEN: The number and characteristics of women who obtain abortions in the United States should continue to be monitored so that trends in induced abortion can be assessed, efforts to prevent unintended pregnancy can be evaluated, and the preventable causes of morbidity and mortality associated with abortions can be identified and reduced.     

The affinity of cholera toxin for Ni2+ ion

Cholera toxin (CT) was shown to bind to immobilized Ni2+ ion. The affinity of CT for the complex required the presence of the Ni2+ ion, since CT was unable to bind in its absence. Binding was mediated by the B-subunit (CTB) as both CT and CTB bound to the resin, but not the A-subunit (CTA). Binding was reversible in the presence of imidazole and suggested that the affinity of CT for the Ni2+ ion was mediated by His residues. The heat-labile enterotoxin of Escherichia coli (LT), which is closely related to CT, was unable to bind to the Ni2+ ion. Comparison of amino acid sequences revealed the presence of three His residues in CT (positions 13, 57 and 94), but only one in LT (position 57). To confirm that the residues at positions 13 and 94 of CTB were responsible for the binding, they were changed to residues found in LTB. Changing His13-->Arg completely abrogated the ability of CTB to bind to Ni2+ ion. In contrast, the mutation of His 94-->Asn reduced, but did not abrogate, the ability of CTB to bind to Ni2+ ion. Based on calculated interatomic distances, it is unlikely that His13 and His94 are part of the same complex. There appear to be two separate binding sites, with the principal site involving His13 and a much weaker site involving His94. This latter site can only participate in binding if the complex involving His13 has formed.     

Adrenomedullin and CGRP receptors mediate different effects in the rat adrenal cortex

Adrenomedullin (AM) exerts its effects through two distinct receptor subtypes: the AM receptor, and the CGRPI receptor. In most tissues activation of these subtypes brings about similar effects, with only the magnitude of the effect varying. In the rat adrenal cortex, however, this does not appear to be the case. Both CGRPI and AM receptors are present in the rat adrenal cortex. Incubation of zona glomerulosa cells with AM caused an increase in aldosterone secretion, but AM had no effect on angiotensin II-stimulated aldosterone secretion. The action of AM was not affected by CGRP8-37, the CGRP receptor antagonist, suggesting that its effect was mediated by the adrenomedullin receptor. CGRP on the other hand, did not significantly affect basal aldosterone although it attenuated the response to angiotensin II. These data suggest that the CGRP receptor and the AM receptor mediate different effects in the rat adrenal zona glomerulosa.     

Idiopathic polypoidal choroidal vasculopathy of the macula

OBJECTIVE: The authors evaluated the clinical, fluorescein, and indocyanine green (ICG) angiographic characteristics of the macular variant of idiopathic polypoidal choroidal vasculopathy (IPCV). DESIGN: Observational case series. PARTICIPANTS: The records, photographs, and fluorescein and ICG angiograms of eight eyes of seven patients with IPCV lesions confined to the macula were reviewed. MAIN OUTCOME MEASURES: The visual acuity, fundus examination, fluorescein and ICG angiographic characteristics, and clinical course were compared. RESULTS: All patients demonstrated polypoidal lesions arising from macular choroidal vessels on ICG angiography. One patient had bilateral lesions. These lesions appeared hyperfluorescent in the early phases of both fluorescein and ICG angiography. Late-phase leakage was seen in cases associated with subretinal fluid or exudate. None of these patients demonstrated polypoidal lesions arising from the peripapillary choroidal circulation or peripapillary choroidal neovascularization. Three eyes with polypoidal lesions that were associated with subretinal fluid and exudates were treated with photocoagulation. Five eyes were not treated. Final visual acuity ranged from 20/20 to hand motions. Severe visual loss was associated with vitreous and subretinal hemorrhage, but this resolved without permanent severe visual loss in several cases. CONCLUSIONS: In the macular variant of IPCV, ICG and fluorescein angiography demonstrate characteristic macular polypoidal lesions without evidence of peripapillary lesions. The vascular origin of these polypoidal lesions appears to be the macular choroidal circulation. This is distinguished from classic IPCV, in which lesions appear to arise from the peripapillary choroidal circulation. Visual prognosis appears to be good, with most patients retaining visual acuity of 20/80 or better. If subretinal fluid or exudates reduce visual acuity, photocoagulation should be considered.     

The role of prior knowledge and elaboration in text comprehension and memory: a comparison of self-generated elaboration and text-provided elaboration

Four experiments investigated the interactive effect of text-provided elaborations and prior knowledge on text comprehension and memory. Subjects read 28 episodes, half of which were associated with well-known people and the other half with unknown people. In Experiment 1, text-provided elaborations enhanced recall only when the reader did not have a high level of prior knowledge. The findings from Experiment 1 were hypothesized to be the result of readers generating relevant elaborations during text comprehension. Experiment 2 supported this hypothesis by providing evidence of self-generated elaborations. The results from Experiments 3 and 4 extended these findings by showing that readers with high prior knowledge automatically generate causally relevant elaborations when the sentences have a low relation.     

Glucose plus insulin infusion improves cerebral outcome after asphyxial cardiac arrest

Hyperglycemia before ischemia worsens cerebral outcome. The aim of this study was to determine the cerebral effects of giving glucose with or without insulin after asphyxial cardiac arrest. Rats underwent 8 min of asphyxial cardiac arrest. After arrest, Group 1 received NaCl; Group 2, insulin; Group 3, glucose; and Group 4, glucose plus insulin, all intravenously. Neurological deficit (ND) scores were 14+/-10%, 22+/-12%, 12+/-10% and 2+/-2% in Groups 1-4, respectively, 72 h after reperfusion. Overall histological damage (HD) scores were 4, 2, 3 and 1, respectively. Group 4 fared significantly better than group 1 on both scores. Glucose after asphyxial cardiac arrest in rats produces no increased brain damage while glucose plus insulin improves cerebral outcome.     

Birth characteristics and asthma symptoms in young adults: results from a population-based cohort study in Norway

There is evidence that the origin of obstructive lung disease may be traced back to foetal life. The associations between birth characteristics and asthma symptoms were studied in a random population sample of young Norwegian adults. Respiratory symptoms were recorded in a population-based questionnaire survey. The records of all subjects aged 20-24 yrs were linked with the Medical Birth Registry of Norway. Of 868 subjects born in Norway, there were 690 (79%) responders. The associations between asthma symptoms and birth characteristics were analysed by logistic regression, adjusted for possible confounding factors. Asthma symptoms in young adults were inversely associated with birth weight (odds ratio (OR)wheeze=0.82; 95% confidence interval (CI)=0.69-0.96x500 g increase in birth weight(-1))), and after adjustment for gestational age, birth length, parity and maternal age (ORwheeze=0.69; 95% CI=0.50-0.95x500 g increase in birth weight(-1)). The association did not vary according to adult smoking habits or atopic status and remained when premature and low weight births were excluded (ORwheeze=0.73; 95% CI=0.60-0.90x500 g increase in birth weight(-1)). The association was consistent for all asthma symptoms. Adjusted for birth weight, asthma symptoms were further associated with low gestational age, high birth length and low maternal age. In a random sample of young adults, asthma symptoms were strongly associated with low birth weight, an association driven by the full-term births within the normal birth weight range. The findings show that the risk for adult asthma is partly established early in life and suggest that poor intrauterine growth is involved in the aetiology of asthma.