An A2-purinoceptor agonist, NECA, potentiates acetylcholine-induced glucagon secretion.

The effect of a stable structural analogue of adenosine, 5'-N-ethylcarboxamidoadenosine (NECA), was studied on glucagon secretion induced by acetylcholine (ACh) in the isolated perfused pancreas of the newborn dog. The perfusion solution contained a physiological concentration of glucose (4.2 mM). In the first set of experiments, ACh (0.5 microM) infused alone for 10 min induced a significant rise of glucagon secretion (370 +/- 98%, 4 min after the beginning of infusion). In the second set, NECA (2.2 nM) infused 10 min before ACh administration, had no effect per se, but considerably increased the response to ACh (929 +/- 262% of basal value within 3 min). So, the more specific A2 purinoceptor agonist, NECA, potentiated glucagon secretion induced by the cholinoceptor agonist, ACh.     

Paracrine renal endothelin system in rats with liver cirrhosis.

1. Liver cirrhosis was induced in rats by CCl4 administration. We analysed the expression of endothelin receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma as well as renal-tissue endothelin-1 concentrations using a specific radioimmunoassay. Furthermore, we analysed the effects of the non-selective (A/B) endothelin receptor antagonist, bosentan (6 and 100 mg kg-1 day-1) on mean arterial blood pressure, water and sodium excretion and glomerular filtration rate. 2. Our study revealed an overexpression of the endothelin B receptor (ETB) in the renal medulla of rats with liver cirrhosis (Cir: 2775 +/- 299 fmol mg-1; Con: 1695 +/- 255 fmol mg-1; n = 8; means +/- s.d., P < 0.01), whereas the density of ETB in the cortex and the endothelin A receptor (ETA) in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. 3. The tissue endothelin-1 concentrations were increased in the renal medulla of cirrhotic rats (Cir: 271 +/- 68 pg g-1wet wt.; Con: 153 +/- 36 pg g-1 wet wt., n = 8; means +/- s.d., P < 0.01). 4. The glomerular filtration rate was slightly decreased in cirrhotic rats but not altered after bosentan treatment in either cirrhotic or control rats. Bosentan decreased sodium excretion to a similar extent in both cirrhotic and control rats, whereas water excretion was significantly reduced by both dosages of bosentan in cirrhotic rats only (Cir + vehicle: 12.5 +/- 0.62 m day-1, Cir + 6 mg kg-1 day-1 bosentan: 8.6 +/- 1.0 ml day-1; Cir + 100 mg kg-1 day-1 bosentan: 7.4 +/- 0.6 ml day-1; n = 10; means +/- s.e.mean). 5. We therefore suggest that the upregulation of the medullary ETB in cirrhotic rats is involved in the regulation of water excretion in rats with CCl4-induced liver cirrhosis.     

What Motivates Participation and Dropout Among Low‐Income Urban Families of Color in a Prevention Intervention?*

Low‐income urban parents of color enrolled in a parent training study were interviewed to understand what motivated their participation and what led 30% of them to subsequently drop out. Most enrolled because they wanted to be better parents. Most dropped out because of time and schedule constraints. Retention was higher when parents' motivations for participation matched program goals. Program location and qualities of the recruiter were cited most often as important; financial compensation was cited least often as important.     

Neonatal rectal colonization with Malassezia furfur

Malassezia furfur and Candida albicans are fungal pathogens which have been recognized with increasing frequency as agents of mortality and serious morbidity in neonatal intensive care unit patients. A longitudinal study of oral, rectal and umbilical colonization by these organisms of newborns admitted to a neonatal intensive care unit within 24 h of birth was undertaken. Of 71 infants followed for a minimum of 10 days, 24 were colonized with M furfur and 12 with C albicans during the first 10 days of life. The lower gastrointestinal tract was found to be the most common colonization site for both organisms. Statistically significant (P<0.05) inverse associations were demonstrated between gestational age and risk of colonization with either organism at any site, and between birthweight or gestational age and risk of rectal colonization with either organism. Antibiotics were associated with a relative risk colonization of 4.06 (P=0.06) with either organism at any site. It is concluded that M furfur and C albicans are common colonizing organisms in a neonatal intensive care unit setting and are most frequently harboured in the lower gastrointestinal tract. M furfur, recently implicated as a systemic pathogen in this population, has not been previously recognized as a gastrointestinal commensal organism. The relationship between colonization and invasive fungal disease, and potential roles for preventive strategies, remain to be elucidated.     

Head injury mortality in two centers with different emergency medical services and intensive care

The authors report data collected prospectively on 551 cases of head injury in New Delhi, India, and 822 cases in Charlottesville, Virginia. The mortality rate, adjusted for initial severity of injury, was 11.0% in New Delhi versus 7.2% in Charlottesville (p less than 0.02). There was a striking similarity in mortality rates at both centers when comparing patients with the least severe head injuries and those with the most severe injuries according to the motor score of the Glasgow Coma Scale (GCS M). However, in the group with an abnormal but purposeful motor response (GCS M = 5), the mortality rate was 12.5% in New Delhi versus 4.8% in Charlottesville (p less than 0.01). The relative absence of prehospital emergency care and the delay in admission after head injury in New Delhi are cited as two possible causes for the differences in mortality rates in this subgroup of patients with "moderate" head injuries.     

Das Verhalten von Blutdruck und Nierendurchblutung während des Carotissinus-Reflexes am wachen Hund

Zusammenfassung An 15 Bastardhunden wurde der Einfluß einer Na-Pentobarbital-Narkose sowei einer zusätzlichen chirurgischen Präparation auf die Ruhewerte von Blutdruck und Nierendurchblutung und deren Änderung nach doppelseitigem Carotisverschluß im Vergleich zum wachen Tier untersucht.Barbiturat-Injektion (30 mg/kg i.v.) allein erhöhte die Herzfrequenz, den systolischen und diastolischen Blutdruck, änderte jedoch nicht die mittlere Nierendurchblutung. Zusätzliche chirurgische Präparation verstärkte diese Veränderungen mit Ausnahme vom systolischen Blutdruck und der Nierendurchblutung.Bei Carotisverschuluß kam es im steady state zu einer vermehrten reflektorischen Herzfrequenzsteigerung nach Barbiturat-Injektion sowie nach Barbiturat mit chirurgischer Präparation. In Barbiturat-Narkose stieg der mittlere Blutdruck stärker an als am wachen Tier; diese Veränderung war nach chirurgischer Präparation noch deutlicher ausgeprägt. Die mittlere Nierendurchblutung wurde im steady state in keiner der 3 Gruppen signifikant verändert. Der reflektorische Herzfrequenz- und Blutdruckanstieg erfolgte im Wachzustand rascher als nach Barbiturat und Barbiturat mit chirurgischem Trauma. Unter letzteren Bedingungen fehlte auch das im Wachzustand beobachtete Unterschießen der Herzfrequenz nach Öffnen der Carotismanschetten. Der druckpassive overshoot der Nierendurchblutung am wachen Tier fehlte sowohl nach Barbiturat als auch nach zusätzlicher chirurgischer Präparation.Die Ergebnisse zeigen, daß der mit Na-Pentobarbitural narkotisierte und der narkotisierte, akut operierte Hund gegenüber dem Wachzustand betreffend der Ruhewerte und der reflektorischen Veränderungen der Herzfrequenz und des Blutdrucks im steady state des Carotissinus-Reflexes zwei quantitativ unterschiedlich reagierende Kreilaufpräparate liefert. Gemessen an der Beseitigung sowohl der raschen Herzfrequenz- und Blutdruckveränderungen als auch des phasischen Einschwingvorganges der Nierendurchblutung durch Narkose und Narkose mit Trauma unterscheiden sich solche Präparate auch qualitativ vom Wachzustand.Mit Unterstützung der Deutschen Forschungsgemeinschaft.     

New provisional serovar (E10163) of Shigella boydii

A long-term outbreak of urinary tract-associated multiply resistant Providencia stuartii occurred in a large medical facility that included a 513-bed chronic care unit. The unique characteristics of this outbreak were that from within a single medical facility, P. stuartii with multiple serotypes, biotypes, and antibiograms could be identified. The organisms isolated had five different biotypes, seven different antibiograms, and two major serotypes. All of the organisms were susceptible to amikacin, cefamandole, and cefoxitin. Application of standard infection control measures impeded the spread of this outbreak, and it slowly terminated 16 months later.     

Nitric oxide participates in the intestinal pathology associated with murine syngeneic graft-versus-host disease

Syngeneic graft-versus-host disease (SGVHD) develops following lethal irradiation, reconstitution with syngeneic bone marrow, and treatment with a short course of cyclosporin A (CsA) therapy. The disease is characterized by the development of a T helper cell type 1-like cytokine response [interleukin (IL)-12, interferon-gamma (IFN-gamma), and tumor necrosis factor alpha], and macrophage activation is central to development of the syndrome. It has been shown that nitric oxide (NO) participates significantly in the development of allogeneic GVHD. Studies were initiated to determine if NO participates in the pathology associated with SGVHD. Significant increases in inducible NO synthase (iNOS) mRNA and circulating NO were found in the tissues of SGVHD versus control animals. Treatment of SGVHD animals with the iNOS inhibitor aminoguanidine (AG) reversed the pathology associated with this disease. Furthermore, AG treatment reduced the production of IL-12 and IFN-gamma mRNA in the colons of CsA-treated mice. These studies demonstrate that NO participates in the pathological processes that are associated with the development of murine SGVHD.     

The Lipopolysaccharide of Bordetella bronchiseptica Acts as a Protective Shield against Antimicrobial Peptides

Resistance profiles of the two Bordetella species B. bronchiseptica and B. pertussis against various antimicrobial peptides were determined in liquid survival and agar diffusion assays. B. bronchiseptica exhibited significantly higher resistance against all tested peptides than B. pertussis. The most powerful agents acting on B. bronchiseptica were, in the order of their killing efficiencies, cecropin P > cecropin B > magainin-II-amide > protamine > melittin. Interestingly, for B. bronchiseptica, the resistance level was significantly affected by phase variation, as a bvgS deletion derivative showed an increased sensitivity to these peptides. Tn5-induced protamine-sensitive B. bronchiseptica mutants, which were found to be very susceptible to most of the cationic peptides, were isolated. In two of these mutants, the genetic loci inactivated by transposon insertion were identified as containing genes highly homologous to the wlbA and wlbL genes of B. pertussis that are involved in the biosynthesis of lipopolysaccharide (LPS). In agreement with this finding, the two peptide-sensitive mutants revealed structural changes in the LPS, resulting in the loss of the O-specific side chains and the prevalence of the LPS core structure. This demonstrates that LPS plays a major role in the resistance of B. bronchiseptica against the action of antimicrobial peptides and suggests that B. pertussis is much more susceptible to these peptides due to the lack of the highly charged O-specific sugar side chains.