Research bronchoscopies do not adversely affect HIV-infected individuals' future health-care decisions

STUDY OBJECTIVES: Asymptomatic HIV-infected individuals are increasingly recruited for studies involving invasive procedures such as bronchoscopy. We sought to determine the response to and outcome of a request for a research bronchoscopy in HIV-positive individuals with no respiratory disease, and whether this would adversely affect future decisions to have a medically indicated bronchoscopy. DESIGN AND SETTING: Prospective, semistructured, questionnaire-based study in a London teaching hospital HIV outpatient clinic. PARTICIPANTS: One hundred and seven consecutive HIV-infected eligible individuals. Thirty-one healthy volunteers served as a control group for the subjective response to bronchoscopy. MAIN OUTCOME MEASURES: Subjects' attitudes and responses to requests for bronchoscopy and subsequent behavior when they required medically indicated bronchoscopy. RESULTS: Seventy-five patients (70%) agreed to the procedure in principle, predominantly for altruistic reasons. Thirty-nine subjects underwent bronchoscopy. Five percent found it worse than expected; and 79% agreed to another research bronchoscopy (performed in 11 subjects approximately 2 years later). All patients said they would undergo bronchoscopy again for diagnostic purposes (required in seven during the study). When compared to a healthy volunteer population within the same study, postbronchoscopy symptoms were similar in frequency although somewhat different in nature. Subjects felt that a clear explanation of what was involved enhanced their participation in this research. CONCLUSIONS: Invasive research procedures such as bronchoscopy can be performed and are repeatable in a healthy HIV-infected population. Performance of procedures for research purposes does not appear to adversely affect future health-care decisions.     

Role of G protein betagamma subunits in muscarinic receptor-induced stimulation and inhibition of adenylyl cyclase activity in rat olfactory bulb

In the olfactory bulb, muscarinic receptors exert a bimodal control on cyclic AMP, enhancing basal and Gs-stimulated adenylyl cyclase activities and inhibiting the Ca2+/calmodulin- and forskolin-stimulated enzyme activities. In the present study, we investigated the involvement of G protein betagamma subunits by examining whether the muscarinic responses were reproduced by the addition of betagamma subunits of transducin (betagamma(t)) and blocked by putative betagamma scavengers. Membrane incubation with betagamma(t) caused a stimulation of basal adenylyl cyclase activity that was not additive with that produced by carbachol. Like carbachol, betagamma(t) potentiated the enzyme stimulations elicited by vasoactive intestinal peptide and corticotropin-releasing hormone. RT-PCR analysis revealed the expression of mRNAs encoding both type II and type IV adenylyl cyclase, two isoforms stimulated by betagamma synergistically with activated Gs. In addition, betagamma(t) inhibited the Ca2+/calmodulin- and forskolin-stimulated enzyme activities, and this effect was not additive with that elicited by carbachol. Membrane incubation with either one of two betagamma scavengers, the GDP-bound form of the alpha subunit of transducin and the QEHA fragment of type II adenylyl cyclase, reduced both the stimulatory and inhibitory effects of carbachol. These data provide evidence that in rat olfactory bulb the dual regulation of cyclic AMP by muscarinic receptors is mediated by betagamma subunits likely acting on distinct isoforms of adenylyl cyclase.     

Cholesterol oxides accumulate in human cataracts

Glucocorticoids induce hyperinsulinemia, hyperglycemia, and depress glucose transport by aortic endothelium. High glucocorticoid doses are used for many diseases, but with unknown effects on brain glucose transport or metabolism. This study tested the hypothesis that glucocorticoids affect glucose transport or metabolism by brain microvascular endothelium. Male rats received dexamethasone (DEX) s.c. with sucrose feeding for up to seven days. Cerebral microvessels from rats treated with DEX/sucrose demonstrated increased GLUT1 and brain glucose extraction compared to controls. Glucose transport in vivo correlated with hyperinsulinemia. Pre-treatment with low doses of streptozotocin blunted hyperinsulinemia and prevented increased glucose extraction induced by DEX. In contrast, isolated brain microvessels exposed to DEX in vitro demonstrated suppression of 2-deoxyglucose uptake and glucose oxidation. We conclude that DEX/sucrose treatment in vivo increases blood-brain glucose transport in a manner that requires the effects of chronic hyperinsulinemia. These effects override any direct inhibitory effects of either hyperglycemia or DEX.     

Prenatal diagnosis of trisomy 13 on fetal cells obtained from maternal blood after minor enrichment

In a pilot study to establish fetal nucleated red blood cell (NRBC) detection in maternal blood, trisomy 13 was diagnosed by FISH analysis at 11 weeks' gestation. The NRBCs were detected after a single-step ficoll density gradient enrichment. In blood samples taken both before and after CVS, 52 and 80 NRBCs, respectively, were found to be positive for fetal haemoglobin. In 47 per cent of these cells, FISH analysis for X and Y chromosomes confirmed the fetal sex. Moreover, 48 per cent of these NRBCs showed three fluorescent signals for a chromosome 13 probe, which confirmed the diagnosis of trisomy 13, previously detected at CVS karyotyping. This is the first report of non-invasive prenatal diagnosis of trisomy 13, i.e., pre-CVS, in the first trimester. The high number of fetal NRBCs detected indicates a connection with aneuploidy, probably due to early impairment of the feto-maternal barrier.     

Peripheral O2 diffusion does not affect V(O2)on-kinetics in isolated insitu canine muscle

To test the hypothesis that muscle O2 uptake (V(O2)) on-kinetics is limited, at least in part, by peripheral O2 diffusion, we determined the V(O2) on-kinetics in 1) normoxia (Control); 2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts the Hb-O2 dissociation curve (Hyperoxia+RSR-13). The study was conducted in isolated canine gastrocnemius muscles (n = 5) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% peak V(O2)). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow (Q), at a level measured at steady state during contractions in preliminary trials with spontaneous Q x Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated Q x Q was measured continuously, arterial and popliteal venous O2 concentrations were determined at rest and at 5- to 7-s intervals during contractions, and V(O2) was calculated as Q x arteriovenous O2 content difference. PO2 at 50% HbO2 saturation (P50) was calculated. Mean capillary PO2 (Pc(O2)) was estimated by numerical integration. P50 was higher in Hyperoxia+RSR-13 [40 +/- 1 (SE) Torr] than in Control and in Hyperoxia (31 +/- 1 Torr). After 15 s of contractions, Pc(O2) was higher in Hyperoxia (97 +/- 9 Torr) vs. Control (53 +/- 3 Torr) and in Hyperoxia+RSR-13 (197 +/- 39 Torr) vs. Hyperoxia. The time to reach 63% of the difference between baseline and steady-state V(O2) during contractions was 24.7 +/- 2.7 s in Control, 26.3 +/- 0.8 s in Hyperoxia, and 24.7 +/- 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement of peripheral O2 diffusion (obtained by increased PcO2 at constant O2 delivery) during the rest-to-contraction (60-70% of peak V(O2)) transition did not affect muscle V(O2) on- kinetics.     

Psychosocial characteristics of pregnant and nonpregnant HIV-seropositive women

Thirty-three HIV-positive women, 12 of whom were pregnant, participated in semistructured interviews to define areas of psychosocial need. Eighty-eight percent of the subjects reported current unemployment. A history of substance abuse was reported by 82 percent, suicide attempts by 52 percent, and sexual problems by 43 percent. Approximately 30 percent reported elevated levels of depressive symptoms on standardized symptom inventories. The pregnant women appeared psychologically healthier than the nonpregnant group. HIV-positive women face multiple psychosocial stressors and may experience significant psychological distress.     

Discovery of a novel tetrahydroacridine acetylcholinesterase inhibitor through an indexed combinatorial library

BACKGROUND: Methods for the rapid and efficient preparation of drug candidates through combinatorial chemistry are of increasing interest. We have previously reported an indexed combinatorial library method that allows both the preparation and testing of compounds in solution. We set out to apply this method to develop more effective analogs of the known, marketed drug tacrine, an acetylcholinesterase inhibitor. RESULTS: A one-step condensation of cyclohexanones with cyanoanilines to generate tetrahydroacridine pools was developed. The resulting library of (formally) 72 tetrahydroacridines was screened against acetylcholinesterase, and a compound 10-fold more potent than tacrine, 7-nitrotacrine, was discovered. Its increased potency could be readily explained by examining the known structure of the complex of acetylcholinesterase with tetrahydroacridine. CONCLUSIONS: In this work, we have provided a relatively rare example of carbon-carbon bond formation in a pool synthesis and have discovered a potentially useful acetylcholinesterase inhibitor.     

Land Use Effect on the CN Model Parameters in a Tropical Dry Environment

Dry tropical forests account for over 1,000,000 km², and there is still lack of knowledge on their hydrologic processes. The curve number (CN) hydrologic model developed by the Natural Resources Conservation Service (NRCS) is widely applied for runoff determination in various parts of the world, but not so in tropical semiarid regions. This study analyzes the impact of land use changes on the CN model in a tropical semiarid environment, in two catchments of native dry tropical forest and thinned dry tropical forest land use from 2009 to 2012. The CN model was calibrated and validated for the NRCS recommended initial abstraction ratio λ = 0.2, and for λ evaluated from rainfall and runoff data. A reliability analysis was performed using Monte Carlo simulation. Model goodness-of-fit was assessed with statistical criteria. A total of 42 and 40 rainfall-runoff events were analyzed for the native and thinned dry tropical forest, respectively. Characteristic λ values of 0.15 and 0.11 were determined for the two respective catchments. Although CN values were similar for both land uses, CN_λ=0.20 = 80 and CN_{median λ} = 77, the thinned catchment showed a higher CN model parameters variability. The CN model was more sensitive to variations of CN values than to those of λ. This study showed that no matter the vegetation management in a dry tropical forest environment, modeled runoff is not affected by λ, but rather affected by CN, which represents soil, landuse and management.     

Effect of catalysts in the quality of syngas and by-products obtained by co-gasification of coal and wastes. 1. Tars and nitrogen compounds abatement

The aim of this work is to analyse the possibility of using co-gasification technology to process coal mixed with wastes to take profit of its energy content and at the same time to minimize the environmental impact associated with the use of wastes and to diminish the costs of flue gas treatment. The addition to coal of different types of materials, like: pine based waste, petcoke and polyethylene (PE), was not found to give rise to any operational problems, regarding both the feeding system and gasification process and led to higher energy conversions, however, the gas presented higher tars and hydrocarbons content. Several catalysts were tested, such as, dolomite, olivine, nickel and magnesium oxides, zinc oxides and cobalt and molybdenum oxides. Catalyst action was analysed in tars release and also in ammonia compounds reduction. The presence of catalysts allowed increasing hydrogen release, whilst there was a decrease in hydrocarbons and tars contents. A nickel-magnesium oxide was the catalyst that led to the highest reduction in hydrocarbons and tars. This catalyst also led to the lowest NH₃ content in the fuel gas produced, due to the catalyst efficiency in NH₃ destruction.     

Evaluation of the thermal and mechanical properties of poly(ε‐caprolactone), low‐density polyethylene,and their blends

The thermal and mechanical properties of low‐density polyethylene (LDPE), poly(ε‐caprolactone) (PCL), and their blends were evaluated. Differential scanning calorimetry showed that increasing the PCL content of the blend did not change the LDPE melting temperature, but reduced the crystallinity by up to 16.8%. This behavior was related to interactions between the PCL chains and the crystalline phase of LDPE. Tensile strength and elongation at break values for the blends were lower than those for the pure polymers, which suggested an incompatibility between the polymers. The values for Young's modulus under tensile increased when PCL was added to LDPE. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91:3909–3914, 2004