Sidestream tobacco smoke exposure acutely alters human nasal mucociliary clearance

Nasal mucociliary clearance (NMC) is a biomarker of nasal mucosal function. Tobacco smokers have been shown to have abnormal NMC, but the acute effect of environmental tobacco smoke (ETS) on nonsmokers is unknown. This study evaluated acute tobacco smoke-induced alterations in NMC in 12 healthy adults. Subjects were studied on 2 days, separated by at least 1 week. Subjects underwent a 60-min controlled exposure at rest to air or sidestream tobacco smoke (SS) (15 ppm CO) in a controlled environmental chamber. One hour after the exposure, 99mTc-sulfur colloid was aerosolized throughout the nasal passage and counts were measured with a scintillation detector. Six out of 12 subjects showed more rapid clearance after smoke exposure than after air exposure, and 3/12 had rapid clearance on both days. However, substantial decreases in clearance occurred in 3/12 subjects, all of whom had a history of ETS rhinitis. In two subjects, more than 90% of the tracer remained 1 hr after tracer administration (2 hr after smoke exposure). Understanding the basis for biologic variability in the acute effect of tobacco smoke on NMC may advance our understanding of pathogenesis of chronic effects of ETS.     

Identification of potent P2Y-purinoceptor agonists that are derivatives of adenosine 5'-monophosphate

1. A series of chain-extended 2-thioether derivatives of adenosine monophosphate were synthesized and tested as agonists for activation of the phospholipase C-linked P2Y-purinoceptor of turkey erythrocyte membranes, the adenylyl cyclase-linked P2Y-purinoceptor of C6 rat glioma cells, and the cloned human P2U-receptor stably expressed in 1321N1 human astrocytoma cells. 2. Although adenosine monophosphate itself was not an agonist in the two P2Y-purinoceptor test systems, eleven different 2-thioether-substituted adenosine monophosphate analogues were full agonists. The most potent of these agonists, 2-hexylthio AMP, exhibited an EC50 value of 0.2 nM for activation of the C6 cell receptor. This potency was 16,000 fold greater than that of ATP and was only 10 fold less than the potency of 2-hexylthio ATP in the same system. 2-hexylthio adenosine was inactive. 3. Monophosphate analogues that were the most potent activators of the C6 cell P2Y-purinoceptor were also the most potent activators of the turkey erythrocyte P2Y-purinoceptor. However, agonists were in general more potent at the C6 cell receptor, and potency differences varied between 10 fold and 300 fold between the two receptors. 4. Although 2-thioether derivatives of adenosine monophosphate were potent P2Y-purinoceptor agonists no effect of these analogues on the human P2U-purinoceptor were observed. 5. These results support the view that a single monophosphate is sufficient and necessary for full agonist activity at P2Y-purinoceptors, and provide insight for strategies for development of novel P2Y-purinoceptor agonists of high potency and selectivity.     

Electronic thermography for the assessment of acute temporomandibular joint pain

Electronic thermography (ET) has the potential to be a nonionizing, noninvasive, low-cost diagnostic alternative for evaluating temporomandibular joint (TMJ) disorders. This study was designed to evaluate the use of ET as a diagnostic aid in the assessment of patients with acute TMJ pain. Computer measurements made using facial thermography were able to distinguish normal patient populations from symptomatic patients with acute TMJ pain. Additional studies are needed before thermographic diagnosis of TMJ disorders will be clinically accepted.     

Granulocyte colony-stimulating factor worsens the outcome of experimental Klebsiella pneumoniae pneumonia through direct interaction with the bacteria

Besides its well-established effects on granulocytopoiesis, granulocyte colony-stimulating factor (G-CSF) has been shown to have direct effects on the recruitment and bactericidal ability of neutrophils, resulting in improved survival of experimentally infected animals. We studied the effect of G-CSF on the course of experimental pneumonia induced by Klebsiella pneumoniae, an important gram-negative bacillary pulmonary pathogen. Using a highly reproducible murine model, we here show the paradoxical finding that mortality from infection was significantly increased when animals received G-CSF before induction of pneumonia. Administration of G-CSF promoted replication of bacteria in the liver and spleen, thus indicating an impairment rather than an enhancement of antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella K2 capsule significantly reduced bacterial multiplication in the lung, liver, and spleen, and abrogated the increased mortality caused by G-CSF. In vitro studies showed a direct effect of G-CSF on K pneumoniae resulting in increased capsular polysaccharide (CPS) production. When bacteria were coincubated with therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing by neutrophils was impaired. Western blot analysis showed three binding sites of G-CSF to K pneumoniae. Binding of 125I-G-CSF to K pneumoniae was displaced by an excess of unlabeled G-CSF, whereas an unrelated cytokine, interleukin-1alpha, did not compete with G-CSF binding to the bacteria. Thus, in this model, the direct effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any beneficial effect of G-CSF on recruitment and stimulation of leukocytes.     

Reduced serotonergic immunoreactive fibers in the forebrain of alcohol-preferring rats

Our previous study indicated that 5-hydroxytryptamine (5-HT) immunoreactive fiber densities were decreased in specific areas of the brain in alcohol-preferring rats (P) when compared with alcohol-nonpreferring rats (NP). The results of our current study show that there are quantitative and qualitative differences in 5-HT innervation in other selected regions of the forebrains of P rats. The 5-HT fiber density in the brains of young adult P and NP rats was measured by immunocytochemistry and quantitative image analysis. A routine error of two-dimensional quantitation of nerve fiber was addressed and an adjustment was made. The amount of 5-HT fibers was significantly lower in CA4 and fasciola cinereum of the dorsal hippocampus, caudate-putamen, and hypothalamus of the P as compared with NP rats (unpaired Student's t tests). In examining the fiber types, we found that, in the frontal cortical and hippocampal regions, where normally fine 5-HT fibers with small varicosities and thick 5-HT fibers with large varicosities coexist, fewer fine 5-HT fibers were seen in P rats as compared with NP rats. The fine fibers are known to be vulnerable to abusive drugs. These observations indicate that (a) there are quantitative differences in 5-HT innervation or that the 5-HT in some 5-HT fibers is reduced to a level undetectable by immunocytochemistry, and (b) the fine 5-HT fibers are specifically reduced to a greater degree in the selected brain regions of P rats when compared with that of NP rats. The involvement of the 5-HT system in the alcohol abuse is discussed.     

Differences in detection of alcohol use in a prenatal population (on a Northern Plains Indian Reservation) using various methods of ascertainment

Although Fetal Alcohol Syndrome (FAS) rates have been reported to be higher in American Indian populations, no screening tool has been validated for alcohol use in American Indian women. The objectives of this study were to compare the detection of prenatal alcohol use by a self-administered questionnaire to detection by clinical interview; and to ascertain whether the screening tool would increase detection of pregnant women who are abusing alcohol. The hospital records of the women were reviewed for any history of alcohol-related illnesses or injuries to compare with results obtained from the questionnaire. Seventy women attending their first prenatal clinic visit on a reservation were screened for alcohol use. There was a wide range in detection of prenatal alcohol use (20%-71% of the sample detected) depending on the method used. There was a large variation in sensitivities (7%-93%) of the individual questions in identifying patients detected as "high risk" by the clinicians. The T-ACE screening questions significantly increased detection of alcohol use compared to detection by the clinicians (p = 0.04 Fisher's exact test). Due to the large variation between different methods of detection, it is recommended that screening tools that increase detection of alcohol use should be combined with methods of higher specificity such as using questions about quantity and frequency of alcohol intake, medical chart review and clinical interview. We also found that various interpretations of the screening questions by the patients highlighted the need to tailor the wording of individual questions to the particular patient population.     

Measurement of rubber cutting resistance in the absence of friction

A method for assessing the resistance of rubbers to cutting by sharp objects is described. It involves the application of the cutting implement -a razor blade-to the tip of a crack in a stretched tear test piece. The method enables effects of friction on the cutting process to be substantially eliminated. Under these conditions two distinct forms of cutting are observed: one is a slow time-dependent process, while the other involves rapid, catastropic failure. Effects of test piece shape and deformation on the cutting behaviour can be taken into account by use of fracture mechanics. The relative cutting resistance of different rubbers is found to vary according to the test conditions. At low deformations the onset of catastrophic cutting can be defined by a simple relationship which is applicable to all rubbers examined.

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Résumé On décrit une méthode pour établir la résistance des caoutchouc à la coupure par des objets affûtés. Cette méthode comporte l'application d'un moyen de coupage (lame de rasoir) à l'extrémité d'une fissure dans une pièce d'essai soumise à déchirement. La méthode permet d'éliminer de manière substantielle les effets de la friction lors du processus de coupure. Sous ces conditions, deux formes distinctes de coupures sont observées: l'une est un processus lent dépendant du temps, tandis que l'autre comporte une rupture rapide et catastrophique. En utilisant la mécanique de la rupture, on peut tenir compte des effets de la forme des pièces d'essai et de la déformation sur le comportement lors du coupage. La résistance relative au coupage de différents caoutchoucs parait varier avec les conditions d'essai. Lors de faibles déformations, le démarrage de la coupure dite catastrophique peut être défini par une relation simple qui est applicable dans tous les cas des caoutchoucs examinés.

     

A transmit/receive IF chip set for WCDMA mobiles in 0.35 /spl mu/m CMOS

An implementation of the IF section of WCDMA mobile transceivers with a set of two chips fabricated in an inexpensive 0.35-/spl mu/m two-poly three-metal CMOS process is presented. The transmit/receive chip set integrates quadrature modulators and demodulators, wide dynamic range automatic gain control (AGC) amplifiers, with linear-in-decibel gain control, and associated circuitry. This paper describes the problems encountered and the solutions envisaged to meet stringent specifications, with process and temperature variations, thus overcoming the limitations of CMOS devices, while operating at frequencies in the range of 100 MHz-1 GHz. Detailed measurement results corroborating successful application of the new techniques are reported. A receive AGC dynamic range of 73 dB with linearity error of less than /spl plusmn/2 dB and spread of less than 5 dB for a temperature range of -30/spl deg/C to +85/spl deg/C in the gain control characteristic has been measured. The modulator measurement shows a carrier suppression of 35 dB and sideband/third harmonic suppression of over 46 dB. The core die area of each chip is 1.5 mm/sup 2/.