Ecotoxicological evaluation of surface waters in Northern Namibia.

The increasing pressure on freshwater systems due to intensive anthropogenic use is a big challenge in central-northern Namibia and its catchment areas, the Kunene and the Kavango Rivers, and the Cuvelai-Etosha Basin, that provide water for more than 1 million people. So far, there is no comprehensive knowledge about the ecological status and only few knowledge about the water quality. Therefore, it is crucial to learn about the state of the ecosystem and the ecological effects of pollutants to ensure the safe use of these resources. The surface waters of the three systems were sampled, and three bioassays were applied on three trophic levels: algae, daphnia, and zebrafish embryos. Additionally, in vitro assays were performed to analyze mutagenicity (Ames fluctuation), dioxin-like potential (micro-EROD), and estrogenicity (YES) by mechanism-specific effects. The results show that acute toxicity to fish embryos and daphnia has mainly been detected at all sites in the three catchment areas. The systems differ significantly from each other, with the sites in the Iishana system showing the highest acute toxicity. At the cellular level, only weak effects were identified, although these were stronger in the Iishana system than in the two perennial systems. Algae growth was not inhibited, and no cytotoxic effects could be detected in any of the samples. Mutagenic effects and an estrogenic potential were detected at three sites in the Iishana system. These findings are critical in water resource management as the effects can adversely impact the health of aquatic ecosystems and the organisms within them.

Tracing the first stars with fluctuations of the cosmic infrared background.

The deepest space- and ground-based observations find metal-enriched galaxies at cosmic times when the Universe was less than 1 Gyr old. These stellar populations had to be preceded by the metal-free first stars, known as 'population III'. Recent cosmic microwave background polarization measurements indicate that stars started forming early--when the Universe was < or =200 Myr old. It is now thought that population III stars were significantly more massive than the present metal-rich stellar populations. Although such sources will not be individually detectable by existing or planned telescopes, they would have produced significant cosmic infrared background radiation in the near-infrared, whose fluctuations reflect the conditions in the primordial density field. Here we report a measurement of diffuse flux fluctuations after removing foreground stars and galaxies. The anisotropies exceed the instrument noise and the more local foregrounds; they can be attributed to emission from population III stars, at an era dominated by these objects.

Developing language skills of cocaine-exposed infants.

OBJECTIVE: To assess whether there is an association of level of fetal cocaine exposure to developmental precursors of speech-language skills at 1 year of age, after controlling for confounding factors. DESIGN: In a prospective, longitudinal, quasi-experimental, matched cohort design, 3 cocaine exposure groups were defined by maternal self-report and infant meconium assay: nonexposure (n = 131), heavier exposure (n = 66), >the 75th percentile for maternal self-report and >the 70th percentile of benzoylecgonine concentration, and all others as lighter exposure (n = 68). At 1 year of age, the Preschool Language Scale-3 was administered by examiners unaware of infant drug status. RESULTS: Independent of confounding drug, medical, and environmental factors, more heavily exposed infants had lower auditory comprehension scores than nonexposed infants and lower total language scores than lighter and nonexposed infants. More heavily exposed infants were also more likely to be classified as mildly delayed by total language score than nonexposed infants. There were positive linear relationships between the concentration of benzoylecgonine in meconium and all outcomes and between maternal report of severity of prenatal cocaine use with poorer auditory comprehension indicating a relationship between amount of exposure and poorer outcomes. CONCLUSIONS: This study documents significant behavioral teratogenic effects of fetal cocaine exposure on attentional abilities underlying auditory comprehension skills considered to be precursors of receptive language. Pediatricians are in a unique position to monitor early development of cocaine-exposed infants and make timely referrals for intervention.

Neurobehavioral outcomes of cocaine-exposed infants.

The present study investigated the neurobehavioral outcomes of fetal cocaine exposure. Attempts were made to control, by design or statistical analysis, for significant confounders. Timing and amount of drug exposures were considered, and biologic measures of exposure were quantified to classify exposure severity. One hundred sixty-one non-cocaine and 158 cocaine-exposed (82 heavily and 76 lightly exposed) infants were seen at a mean-corrected age of 43 weeks post-conception and administered the Neurobehavioral Assessment (NB Assessment). Heavily cocaine-exposed infants had more jitteriness and attentional problems than lightly and non-exposed infants. They also had more movement and tone abnormalities, and sensory asymmetries than non-exposed infants. Heavily exposed infants were more likely to be identified with an abnormality than non-exposed infants and there was a trend toward heavily exposed infants being more likely to be identified with an abnormality than lightly exposed infants. Furthermore, there was a trend for heavily exposed infants to be less likely to be testable than non-exposed infants. After the confounding and mediating factors were considered, heavily cocaine-exposed infants were four times as likely to be jittery and nearly twice as likely to demonstrate any abnormality than lightly and non-exposed infants, but all other effects were no longer significant. Higher concentrations of the cocaine metabolites of cocaine, cocaethylene, and benzoylecgonine (BZE) were related to higher incidence of movement and tone abnormalities, jitteriness, and presence of any abnormality. Higher cocaethylene levels were related to attentional abnormalities and higher meta-hydroxybenzoylecgonine (m-OH-BZE) was related to jitteriness. Drug effects on attention were mediated by maternal psychological distress, suggesting that this factor should be considered in future studies of drug exposure effects.

Endothelin in coronary endothelial dysfunction early after human heart transplantation.

BACKGROUND: Cytokines and growth factors released as part of the immune response to alloantigenic stimuli are capable of regulating endothelin-1 expression in the allograft. Endothelin plays a significant role as a modulator of coronary vascular reactivity in the early stages of atherosclerosis and may be important as a participant in and marker for cardiac allograft vasculopathy. METHODS: We characterized a possible relationship between morphological and functional coronary changes, transcardiac plasma endothelin level and myocardial endothelin-mRNA expression in 33 cardiac transplant recipients in the early, stable phase 5+/-3 months after orthotopic heart transplantation. Coronary microvascular function was determined as endothelium-dependent with acetylcholine and endothelium-independent with adenosine using intracoronary Doppler-FloWire. The percentage of the epicardial diameter changes was measured using quantitative coronary angiography. Intravascular ultrasound was performed to quantify intimal hyperplasia. Cardiac endothelin uptake or release was determined by measuring plasma endothelin levels in the coronary sinus and aorta. Myocardial endothelin-gene expression was determined using semiquantitative RT-PCR. RESULTS: The aortic endothelin levels were significantly increased in transplant recipients compared to nontransplanted patients (11.8+/-2.2 vs 7.2+/-0.9 fmol/mL; P < 0.001). Endothelin uptake was noticed in the majority of patients, and the amount of endothelin uptake was correlated to microvascular (r = 0.37; P < 0.05) and epicardial (r = 0.41; P < 0.03) endothelium-dependent vasodilatation. High mRNA signal intensity was associated with significantly reduced coronary flow response to acetylcholine compared to patients with low myocardial gene expression (coronary flow reserve 2.4+/-0.9 vs 3.4+/-0.8, respectively; P < 0.005). Morphological coronary changes early after transplantation were not correlated to endothelin plasma levels or myocardial gene expression. CONCLUSION: Coronary endothelial vasomotor dysfunction after cardiac transplantation is associated with an increased myocardial endothelin mRNA expression and decreased endothelin-uptake by the heart. We postulate that early activation in the endothelin system may have a pivotal role in the acceleration of the atherosclerotic process in transplant patients.

Motor development of cocaine-exposed children at age two years.

OBJECTIVE: This article was designed to investigate effects of prenatal cocaine exposure on motor development of young children from a predominately underprivileged, urban population. METHODOLOGY: A total of 260 infants and young children were initially recruited from either the newborn nursery or the at-risk pediatric clinic of an urban teaching hospital. Prenatal history and birth outcomes were collected from medical records. Demographic characteristics and additional drug histories were obtained from the mothers. The 199 subjects (98 cocaine-exposed and 101 unexposed) who returned at age 2 years were assessed by examiners blinded to drug exposure status using the Peabody Developmental Motor Scales. RESULTS: Compared with control subjects, the cocaine-exposed group performed significantly less well on both the fine and the gross motor development indices. Mean scores for both groups were within the average range on the gross motor index, but greater than 1 standard deviation below average on the fine motor index. Differences were significant on the balance and the receipt and propulsion subscales of the gross motor scale, and on the hand use and the eye-hand coordination subscales of the fine motor scale. Cocaine status independently predicted poorer hand use and eye-hand coordination scores. There also was an effect of alcohol exposure on the receipt and propulsion subscale. CONCLUSIONS: Findings indicate that deficiencies in motor development remain detectable at 2 years of age in children exposed to drugs prenatally. Although other environmental variables may influence motor development, children exposed to cocaine and to alcohol in utero may encounter developmental challenges that impede later achievement.

Cocaine increases the endothelial release of immunoreactive endothelin and its concentrations in human plasma and urine: reversal by coincubation with sigma-receptor antagonists.

BACKGROUND: Cocaine-associated vascular events are not completely explained by adrenergic stimulation. The purposes of this study were to investigate whether vasoconstrictive endothelin-1 is released by cocaine and to elucidate the mechanisms involved. METHODS AND RESULTS: Endothelin-1 was measured by radioimmunoassay and high-performance liquid chromatography (1) in the supernatant of porcine aortic endothelial cells after treatment with cocaine (10(-7) to 10(-4) mol/L) and a sigma-receptor antagonist, haloperidol (10(-6) mol/L) or ditolylguanidine (10(-5) mol/L) and (2) in plasma and urine of 12 cocaine-intoxicated patients and 13 healthy control subjects. Radioligand binding assays were performed on endothelial membrane preparations. In cell culture, cocaine significantly increased endothelin accumulation above baseline at 3 to 24 hours; endothelin release rates per hour increased dose-dependently, reaching a plateau of 175+/-23% of control at hour 4 to 5. Coincubation of cocaine with haloperidol or ditolylguanidine abolished or reduced cocaine-induced endothelin release. Endothelial membrane preparations specifically and displaceably bound the highly selective sigma-ligand [3H]ditolylguanidine (25x10(-9) mol/L), with 1400 binding sites estimated per cell. Endothelin-1 levels in plasma (22.7+/-5.6 versus 7.3+/-0.8 pmol/L) and urine (41.5+/-10.1 versus 12.7+/-3.8 pmol/L) of cocaine-intoxicated patients were significantly increased compared with control values. CONCLUSIONS: The data suggest that cocaine increases the endothelin-1 release in vitro and in vivo. The cocaine-induced vasoconstriction/vasospasm may therefore be facilitated by the release of endothelin-1. Cocaine appears to be an exogenous stimulator at endothelial sigma-receptors. The endogenous ligands of this antiopioid system may prove to play a role in vasospastic angina, acute myocardial infarction, and sudden cardiac death.

Endothelin B receptor-mediated increase of cerebral blood flow in experimental pneumococcal meningitis.

Study investigates the role of endothelin (ET) receptors in mediating early changes in cerebral blood flow--as measured by laser Doppler flowmetry (CBFLDF)--during experimental pneumococcal meningitis. Meningitis was induced with heat-killed pneumococci and confirmed by a significant increase in CBFLDF (baseline 100%; 225.3 +/- 21.8% after 6 hours; mean +/- SD), intracranial pressure (ICP), brain water content, and white blood cell count in the CSF. Intravenous administration of the selective endothelin B (ETB) receptor antagonist BQ-788 immediately before pneumococcal challenge (but not 4 hours afterward) significantly attenuated these pathophysiologic alterations (e.g., CBFLDF 6 hours after pneumococcal challenge: 116.7 +/- 17.4%). Pretreatment with BQ-123, a selective endothelin A receptor antagonist, had no significant effect on ICP and brain water content, but augmented the increase in CBFLDF and CSF white blood cell count. Since ET is known to trigger the release of nitric oxide (NO) by ETB receptor activation, we examined specific ET-NO interactions in primary rat cerebromicrovascular endothelial cells after stimulation with heat-killed pneumococci. Pneumococci induced a significant increase in both ET and NO concentrations in endothelial cell culture medium. Treatment with phosphoramidon, an inhibitor of the endothelin-converting enzyme, prevented the production of endothelin and markedly reduced NO generation. Our data provide evidence that ET is involved as a mediator in early pneumococcal meningitis in the rat and contributes to the increase in CBFLDF, ICP, brain water content, and CSF pleocytosis, presumably through ETB receptor-mediated NO production.

Relationship of prenatal cocaine exposure and maternal postpartum psychological distress to child developmental outcome.

Maternal cocaine use during pregnancy can affect the infant directly through toxic effects or indirectly through cocaine's influence on maternal psychological status. We followed 160 cocaine exposed and 56 nonexposed infants and their mothers identified at birth through interview and/or urine screen. Although cocaine exposure defined the groups, infant exposure to alcohol, marijuana, and tobacco was allowed to vary. Infants were 99% African American and poor. All mothers completed the Brief Symptom Inventory (BSI) and infants were given the Bayley Scales of Mental (MDI) and Motor (PDI) Development at a mean corrected age of 17 +/- 8 months. Both MDIs (94 +/- 17 vs. 103 +/- 16) and PDIs (101 +/- 16 vs. 108 +/- 12) were lower for cocaine exposed infants. Psychological distress was greater in cocaine using mothers. Hierarchical multiple regression was used to assess the relative effects of gestational age, maternal psychological distress, and cocaine and polydrug exposure on infant outcomes. Both psychological distress and cocaine and alcohol exposure predicted lower MDIs after controlling for prematurity. Neither psychological distress nor alcohol exposure predicted motor outcome, while cocaine had a significant effect. Tobacco and marijuana exposure were unrelated to outcome. These findings provide further support for direct effects of cocaine and alcohol on infant development as well as highlight the need for studies to document maternal psychological factors, which may increase child risk for poorer outcomes.

[Necrotizing fasciitis]. / Die nekrotisierende Fasziitis.

Necrotizing fasciitis has changed considerably over time. The disease used to be due to group A streptococci and affected otherwise quite healthy or traumatized subjects. Today we see multibacterial infections in polymorbid or immunocompromised patients. Rapid and resolute surgery is of critical prognostic value. Early clinical recognition may be difficult. Sometimes frozen-section biopsy proves helpful. Septic immune response and organ failure develop rapidly in these patients. After vigorous staged necrosectomy, extensive plastic reconstruction is mostly required.

Prevention of hyperacute rejection by human decay accelerating factor in xenogeneic perfused working hearts.

As a potential source of organs for xenotransplantation, pigs that are transgenic for human decay accelerating factor (DAF) have been bred in order to overcome hyperacute rejection. We investigated the protective effect of human DAF in a porcine working heart model perfused by human blood. Hearts of normal landrace pits served as controls. The following parameters were measured: stroke work index, coronary flow and arteriovenous oxygen consumption, 6-keto prostaglandin F1alpha and prostaglandin E2 as markers of endothelial cell activation; creatine phosphokinase and lactate dehydrogenase for evaluation of the extent of myocardial damage; TNFalpha and IL-6 as markers of mononuclear cell activation. Histological and ultrastructural investigations from myocardial tissue sections were done at the end of perfusion. Human (h) DAF appeared to inhibit complement-mediated endothelial cell activation of transgenic pig hearts successfully. This was in contrast to landrace pig hearts, which had a sixfold increase of prostaglandin levels during perfusion with human blood. The cardiac weight increase during perfusion time due to interstitial edema tended to be less in the hDAF group. Myocardial damage was minimal in transgenic hearts, whereas normal pig hearts produced a threefold increase of creatine phosphokinase and lactate dehydrogenase levels. In these hearts, electron microscopy revealed single cell necrosis of myocytes and vacuolization of mitochondria with cristae rupture. According to the results obtained in the working heart model, the breeding of pigs that are transgenic for hDAF represents a promising step to making heart xenotransplantation a clinical reality in the future.

Mothers touching newborns: a comparison of rooming-in versus minimal contact.

We compared the maternal behaviors of women who had extended and early contact (rooming-in) with their infants with those who had contact only during feedings. Thirty-one young, unmarried, predominantly black, lower-socioeconomic mothers and their infants were observed in the mother's hospital room for 15 minutes after a morning feeding approximately 18 hours after delivery. A time sample unit checklist was used to record each mother's behavior, looking, talking, and touching directed toward their infants and others, as well as watching television and talking on the telephone. Analyses of variance revealed that the rooming-in mothers looked at, talked to, and touched their infants more, watched less television, and talked less on the telephone than mothers with minimal contact with their infants. These findings suggest that increased postpartum contact with infants leads not only to more interaction, but also to more touching as well as touching in more intimate places (face and head), thus highlighting the value of rooming-in arrangements for mothers and infants.

Increased psychological distress in post-partum, cocaine-using mothers.

This study investigated psychological symptoms, self-reported postpartum by poor, primarily African American women who used cocaine during pregnancy. Ninety-nine cocaine-using mothers (COC+) were compared to 44 noncocaine-using mothers (COC-) on standardized measures of psychological distress and verbal comprehension. Mothers were interviewed to determined extent of drug involvement. COC+ mothers reported using alcohol, marijuana, and tobacco at two to three times the rate of comparison mothers during pregnancy and reported earlier initiation of marijuana use. COC+ women were more likely to admit to interpersonal difficulties and to report phobic anxiety and paranoid ideational symptoms. The COC+ group was also more likely to have clinically elevated scores on subscales indicating feelings of personal inadequacy, phobic anxiety, and paranoia. The use of cocaine, in combination with either alcohol or marijuana, was the best predictor of psychoticism, hostility, and total number of distress symptoms.

Bidirectional effects of endogenous opioid peptides on endothelin release rates in porcine aortic endothelial cell culture: mediation by delta opioid receptor and opioid receptor antagonist-insensitive mechanisms.

The effects of opioid peptides on immunoreactive endothelin (ir ET) release from cultured porcine aortic endothelial cells over a 1-hr period (4-5 or 23-24 hr) were determined by radioimmunoassay and high-performance liquid chromatography after treatment for either 4 or 23 hr. Endogenous opioids, the synthetic delta opioid [D-Pen2,5]enkephalin and, for comparison, atrial and brain natriuretic peptides were added to the culture medium in concentrations ranging from 10(-12) to 10(-7) M. Thrombin (0.1-10 U/ml) served as a stimulatory reference. 1) Brain natriuretic peptide displayed only insignificant effects on ir ET release at 5 hr, but strongly inhibited ir ET release at 24 hr. 2) Opioids modulated release rates at 5 hr but did not display significant effects at 24 hr: metorphamide with predominant mu/kappa and weak delta opioid receptor activity stimulated release in a dose-dependent manner, whereas [Met5]enkephalin-Arg6-Phe7 with mu/delta activity and the delta agonists [Leu5]enkephalin, sulfated [Leu5]enkephalin and [D-Pen2,5]enkephalin decreased release rates; [Leu5]enkephalin was the most potent of the latter drugs. 3) Coincubation with either the nonselective opioid receptor antagonist naloxone (10(-5) M) or the delta receptor-selective antagonist ICI-174,864 (N,N-bisallyl-Tyr-D-Ala-Aib-Aib-Phe-Leu-OH) (10(-5) M) abolished all opioid-induced inhibitory effects, but rather potentiated or unmasked stimulatory effects of opioid peptides on ir ET release rates at 5 hr and also at 24 hr in the case of the delta agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct and indirect interactions of cocaine with childbirth outcomes.

OBJECTIVE: To evaluate neonatal sequelae of maternal cocaine use during pregnancy. METHODS: One hundred women positive for cocaine use during pregnancy were compared with 100 matched controls who did not use cocaine. Maternal characteristics and infant neonatal outcomes were compared. We used t tests, chi 2, and multiple regression analyses to evaluate the contributions of cocaine vs other drugs to outcome. RESULTS: Cocaine was the best predictor of increased incidence of abortions, higher maternal gravidity, and poorer prenatal care. Cocaine was also the best predictor of preterm birth and of lower birth weight, after controlling for prematurity. Maternal use of cocaine and alcohol in combination was the best predictor of decreased linear growth, after controlling for prematurity. CONCLUSIONS: Maternal cocaine use predicts negative birth outcomes directly, as well as through obstetric risk factors of abortion history and less prenatal care. Interactive effects of cocaine and alcohol should be considered in future studies of birth outcomes.