Effects of hypoxia on the hemodynamic actions of prostaglandin E1

The effect of prostaglandin E1 (PGE1) on central and peripheral hemodynamics was studied in seven conscious dogs under conditions of normoxia and hypobaric hypoxia to ascertain if hypoxia attenuated the cardiovascular actions of PGE1. Silastic catheters were chronically implanted in the pulmonary artery, left atrium, and aorta. Acute hypoxia was produced in a hypobaric chamber maintained at 446 mmHg pressure (14,000 feet). PGE1 at sea level (normoxia) resulted in significant increases in heart rate, cardiac output, left ventricular stroke work and pulmonary blood volume as well as significant decreases in aortic, pulmonary arterial, and left atrial pressures. During hypobaric hypoxia, PGE1 produced essentially identical effects on all hemodynamic parameters except pulmonary blood volume and pulmonary arterial pressure where marked attenuation of PGE1 action occurred.     

Recurrent hypernatremia; a proposed mechanism in a patient with absence of thirst and abnormal excretion of water

A 7-year-old girl twice developed severe hypernatremia (serum sodium values up to 194 mEq/l) without obvious cause. The ability of her kidneys to conserve water was normal, and increasing her plasma osmolality stimulated an appropriate ADH response. Unable to excrete a water load, her kidneys continued to conserve water even with a serum sodium concentration of 133 mEq/l. She was never thirsty and did not ingest sufficient fluid by choice. Although there was no demonstrable anatomic lesion, we postulate a localized defect of her thirst center. This may have modified release of ADH and resulted in an inability to dilute the urine by interrupting a pathway that could exist from the thirst center to the supraoptic nuclei. A therapeutic regimen based on these studies has prevented further hypernatremia.     

Propranolol therapy in patients undergoing myocardial revascularization

The records of 185 consecutive patients having myocardial revascularization were reviewed with regard to preoperative administration of propranolol and intraoperative or postoperative complications. Tachycardia and hypertension before cardiopulmonary bypass were slightly more common in patients never taking propranolol or those who had discontinued it for more than 48 hours before operation. There was no statistically significant difference in the incidence of postbypass hypotension among patients who took propranolol within 24 hours of operation, those who discontinued it more than 24 hours before operation, and those who never took the drug. Operative mortality was not significantly different among patients who received propranolol within 48 hours of operation (3%), those who never took it and those who discontinued it more than 48 hours before operation (4%). Early in the series, five patients had an acute myocardial infarction within 48 hours after routine preoperative withdrawal of propranolol. Because complete withdrawal of propranolol in patients with unstable angina pectoris may lead to acute myocardial infarction, we recommend gradual withdrawal of the drug during 48 hours before operation. If this is not possible because anginal pain recurs or intensifies, then reduced doses may be given safely up to 10 hours before revascularization, provided that the patient is a satisfactory candidate for bypass and that adequate myocardial revascularization can be accomplished.     

Development of attention in preterm infants

The quality of the awake state and attention in preterm infants has been evaluated by rating indices of attention such as widening of the eye, type of fixation, brightening, scanning, and cessation of sucking measured during visual fixation of patterns. Twenty-six infants ranging from 28 to 32 weeks' gestation at birth (mean, 31 weeks) were tested from one to four weeks postnatally until 36 weeks' gestation. Indices of attention were rated on a scale of 4 with an optimal mean index of 4. A progressive increase in behaviors associated with fixation of visual stimuli has been shown from 32 to 36 weeks of conceptual age. Mean scores ranged from 0.7 at 31 weeks' gestation to 1.8 at 34 weeks' and 2.7 at 36 weeks' gestation. The possibility therefore exists that by as early as 31 to 32 weeks from conception the human brain may be capable of waking states and thus able to process some sensory stimulation.rease in behaviors associated with fixation of visual stimuli has been shown from 32 to 36 weeks of conceptual age. Mean scores ranged from 0.7 at 31 weeks' gestation to 1.8 at 34 weeks' and 2.7 at 36 weeks' gestation. The possibility therefore exists that by as early as 31 to 32 weeks from conception the human brain may be capable of waking states and thus able to process some sensory stimulation.     

The exotoxin of Bacillus thuringiensis: a new C-mitotic agent

Thuringiensin A, an exotoxin from Bacillus thuringiensis, a constituent of the microbial insectide thuricide has been found to inhibit mitotic spindle, condense and scatter chromosomes. It may therefore be a promizing tool in future cell biological studies.     

The applicability of the flow cytometric sperm chromatin structure assay in epidemiological studies. Asclepios

The impact of demographic, lifestyle, and seminal factors on the sperm chromatin structure assay (SCSA) parameters was evaluated in a population of 277 healthy Danish men. This cohort was established within the framework of a European Concerted Action on occupational hazards to male reproductive capability in order to examine the possible reproductive effects of exposure to styrene or pesticides. The SCSA measures the susceptibility of sperm DNA to in-situ acid-induced denaturation, by multiparameter flow cytometric analysis after staining with the DNA-specific fluorescent dye acridine orange. The green versus red bivariate cytogram patterns were quite variable among donors, showing a wide heterogeneity of sperm DNA denaturability. Nevertheless, in those cases where we had the possibility to measure two semen samples from the same donor, the cytogram pattern remained stable over time (0.64 < r < 0.78). Analysis of variance demonstrated that the SCSA results can be influenced by the age of the donor (P < 0.0001), smoking habits (P < 0.05), the presence of leukocytes and immature germ forms in the ejaculate (P < 0.0001), and the duration of sexual abstinence (P < 0.0001). Furthermore, the relationship between the SCSA data and sperm concentration, morphology, and vitality was weak (-0.22 < r < -0.46). Therefore, the SCSA provides independent and complementary measurements of semen quality and is thus a useful tool for epidemiological studies, but the effects of some confounders should be accounted for in the survey design and analysis.     

Surfactant nebulization versus instillation during high frequency ventilation in surfactant-deficient rabbits

Glutamate-mediated excitotoxicity plays an important role in the degeneration of nigrostriatal dopamine (DA) neurons induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), although the role of the N-methyl D-aspartate (NMDA) receptor subtype in this process is still uncertain. We studied glutamate receptor subtype agonist-induced ionic currents in acutely dissociated DAergic neurons from the rat substantia nigra zona compacta (SNc) using the nystatin-perforated patch-clamp whole-cell recording technique. The results fall into four main categories. First, single neurons, freshly isolated from SNc, exhibited a large soma and multipolar morphology, responded to DA, and stained positively for tyrosine hydroxylase (TH). Second, rapid application of L-glutamate (> 10(-5) M) induced an inward current with minimal desensitization at a clamp voltage of -60 mV. Third, kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-isoxazole (AMPA) induced an inward current that was similar to the glutamate-induced current while, in the same neuron, NMDA (10(-4) M) failed to induce any current response in Mg2+-free solution that contained 10(-5) M glycine at a clamp voltage of -60 mV. Under the same experimental conditions, NMDA induced a clear current response in isolated substantia nigra reticulata (SNr) neurons. Fourth, the specific NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV, 10(-4) M) failed to block 10(-4) M glutamate-induced inward current, while the specific KA/AMPA receptor antagonist 6-cyano-7-nitroguinoxaline-2, 3-dione (CNQX, 10(-5) M) completely blocked the glutamate-induced current. These results indicate that in single SNc DAergic neurons of 2-week-old rats, L-glutamate-induced inward current is mediated by non-NMDA receptors rather than by NMDA receptors.     

Homeless youth and their exposure to and involvement in violence while living on the streets

Sick building syndrome is the term given to a heterogeneous constellation of symptoms that affects workers in modern mechanically ventilated office buildings. Although the cause is unknown, there is evidence that the local environment of the work station is an important determinant of symptoms. In this study, investigators examined the effect of a new, individually controlled ventilation system on workers' symptoms. Investigators studied two groups of workers in one mechanically ventilated office building: (1) a control group at whose worksite no intervention was made and (2) an intervention group. The intervention consisted of installation of a device that allowed each worker control over the ventilation supplied to his or her worksite. Just before, and 4 and 16 mo after installation of this device, workers completed self-administered questionnaires regarding occurrence of symptoms. The new ventilation system resulted in higher air velocities, more variable temperatures, and higher concentrations of airborne dust and fungal spores. Four months after installation, workers with the new ventilation system reported fewer symptoms that were (a) work-related (p < .05) and that were work-related and frequent (p < .05); in addition, they reported fewer symptoms that reduced their capacity to work (p < .01). Sixteen months after installation, workers with the new device reported fewer symptoms than at baseline (although not as significantly), and they indicated that the indoor air quality improved their productivity by 11%, compared with a 4% reduction of productivity among the control group of workers (p < .001). Investigators concluded that the new ventilation system, which provided the workers with individual control over ventilation, was associated with important and sustained reduction in symptoms.     

Click‐ligation of coumarin to polyether polyols for polyurethane foams

A simple strategy for the synthesis and functionalization of polyurethanes is described. Anionic ring‐opening polymerization was combined with ‘click’ chemistry to synthesize polyols with fluorescent properties. This route allows the incorporation of a wide range of functionalities in the polyols with an easy, clean and highly selective process compatible with several types of functional groups. The proposed strategy opens the way to the production, in a cost‐effective way, of ‘smart’ polyurethanes with non‐conventional properties like fire retardancy, antimite properties, antibacterial properties, etc. Alkynyl groups were introduced into the polyol chains by the controlled addition of glycidyl propargyl ether as co‐monomer during a conventional anionic ring‐opening copolymerization with propylene oxide. Subsequently 4‐azidomethyl‐7‐methoxycoumarin molecules were introduced onto the alkynyl‐polyether polyols by copper‐catalysed cycloaddition reactions to produce end‐functionalized polyols. The chemical structure of the novel polyols was characterized using infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography with triple detection and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy. These characterization techniques confirmed the presence of a considerable amount of functional groups in the structure of the polyols. Finally, various fluorescent rigid foams, based on the functionalized polyols, were synthesized. Copyright © 2012 Society of Chemical Industry     

Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of beta-amyloid and prion proteins

Microglial interaction with amyloid fibrils in the brains of Alzheimer's and prion disease patients results in the inflammatory activation of these cells. We observed that primary microglial cultures and the THP-1 monocytic cell line are stimulated by fibrillar beta-amyloid and prion peptides to activate identical tyrosine kinase-dependent inflammatory signal transduction cascades. The tyrosine kinases Lyn and Syk are activated by the fibrillar peptides and initiate a signaling cascade resulting in a transient release of intracellular calcium that results in the activation of classical PKC and the recently described calcium-sensitive tyrosine kinase PYK2. Activation of the MAP kinases ERK1 and ERK2 follows as a subsequent downstream signaling event. We demonstrate that PYK2 is positioned downstream of Lyn, Syk, and PKC. PKC is a necessary intermediate required for ERK activation. Importantly, the signaling response elicited by beta-amyloid and prion fibrils leads to the production of neurotoxic products. We have demonstrated in a tissue culture model that conditioned media from beta-amyloid- and prion-stimulated microglia or from THP-1 monocytes are neurotoxic to mouse cortical neurons. This toxicity can be ameliorated by treating THP-1 cells with specific enzyme inhibitors that target various components of the signal transduction pathway linked to the inflammatory responses.