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PubMed1997

Oscillatory pressure transients after flow interruption during bronchial challenge test in children.

The measurement of the conventional interrupter resistance (Rint) is dependent on pressure equilibration between alveolar and airway opening pressure, which is often not achieved in the presence of severe airways obstruction or in small children. The damping properties (d) of postocclusional oscillatory pressure transients after rapid flow interrruption can be assessed independent of complete pressure equilibration, and we have previously shown them to be correlated to resistive properties of the respiratory system. We wanted to determine whether these transients were an expression of acoustic properties of the air in the airways, or whether they were caused by an interaction of gas and lung tissue, and whether d was more sensitive than Rint to changes in airway mechanics. Bronchial challenge tests were carried out with cumulative doses of inhaled carbachol in 10 healthy children (aged 7-14 yrs) and 50 asthmatic children (aged 5-15 yrs). The airflow interruptions were performed with a combined nebulizer-shutter head, allowing resistance measurements with each breath. The frequency, and the damping factor of the postocclusional pressure transients changed significantly during carbachol challenge in both groups of children. The provocation dose (PD) at which the damping factor (d) of the oscillatory pressure transients increased more than 2 SD above the baseline mean ("variance-based", PDvb) was lower than the PDvb of the end-interruption resistance (Rint, EI). These changes in frequency and damping factor were reversible after inhaling salbutamol. These findings suggest that the damping properties of the postocclusional pressure transients after flow interruption can be used as a sensitive parameter to assess changes in airway mechanics during bronchial challenge test in children in whom pressure equilibration is frequently not achieved during airflow interruption due to airways obstruction.

Acoustics↗

PubMed2003

Egg hatching, larval movement and larval survival of the malaria vector Anopheles gambiae in desiccating habitats.

BACKGROUND: Although the effects of rainfall on the population dynamics of the malaria vector Anopheles gambiae have been studied in great detail, the effects of dry periods on its survival remain less clear. METHODS: The effects of drying conditions were simulated by creating desiccated habitats, which consisted of trays filled with damp soil. Experiments were performed in these trays to (i) test the ability of An. gambiae sensu stricto eggs to hatch on damp soil and for larvae to reach an artificial breeding site at different distances of the site of hatching and (ii) to record survival of the four larval stages of An. gambiae s.s. when placed on damp soil. RESULTS: Eggs of An. gambiae s.s. hatched on damp soil and emerging larvae were capable of covering a distance of up to 10 cm to reach surface water enabling further development. However, proportions of larvae reaching the site decreased rapidly with increasing distance. First, second and third-instar larvae survived on damp soil for an estimated period of 64, 65 and 69 hrs, respectively. Fourth-instar larvae survived significantly longer and we estimated that the maximum survival time was 113 hrs. CONCLUSION: Short-term survival of aquatic stages of An. gambiae on wet soil may be important and adaptive when considering the transient nature of breeding sites of this species in sub-Saharan Africa. In addition, the results suggest that, for larval vector control methods to be effective, habitats should remain drained for at least 5 days to kill all larvae (e.g. in rice fields) and habitats that recently dried up should be treated as well, if larvicidal agents are applied.

Animals↗

PubMed1999

Function of M3 muscarinic receptors in the rat urinary bladder following partial outlet obstruction.

PURPOSE: Partial outlet obstruction of the rat urinary bladder leads to hypertrophy and alteration in contractility of the detrusor muscle involving changes in muscarinic receptors. m3 muscarinic receptor subtype has been known to play a predominant role in contractility of normal urinary bladder. The purpose of the present study was to assess the role of m3 receptors in contractility of the obstructed bladder. MATERIALS AND METHODS: In male rats, partial outlet obstruction of the urinary bladder was performed by surgically tying a 6-0 suture around the bladder neck, reducing the diameter of it by 2/3 of the original size. Four weeks after the surgery, the bladders were removed and thin strips were microdissected. Similarly, bladder strips from age matched unoperated normal rats were obtained. Sets of four strips from four normal or four obstructed rats were mounted in an in vitro multi-muscle chamber containing normal physiological solution at 37C. The tension responses evoked by optimal electrical field stimulation at 1, 10, 30, 50, and 100 Hz, and the contracture responses evoked by 120 mM potassium and 0.01 to 300.0 microM carbachol were recorded using a Nicolet digital oscilloscope. Similar responses were recorded in different sets of four strips following exposure to 10 and 100 nM 4-DAMP, which is a muscarinic antagonist with a high affinity for m3 and m1 receptor subtypes. RESULTS: The obstructed bladders showed 119% increase in weight. In control physiological solution, the obstructed bladder strips did not show significant difference in electrically-evoked tension or carbachol contractures, but showed significantly lower potassium contractures compared with normal bladder strips. 4-DAMP at 10 to 100 nM significantly reduced the electrically evoked tension responses by about the same degree in normal and obstructed bladders, without affecting the potassium contractures. It significantly increased the EC50 values for carbachol contractures in normal bladder, and to a significantly lesser extent in obstructed bladder. Schild plots using the Hill transformed EC50 values showed that the pA2 value for 4-DAMP was not significantly different in normal and obstructed bladders. CONCLUSIONS: Significantly smaller potassium contracture in the obstructed bladder indicates that depolarizability of the detrusor muscle membrane, and consequently the activity of voltage-gated Ca2+ channels may be reduced in the detrusor after partial outlet obstruction. Lack of a significant difference in the effect of 4-DAMP on the electrically evoked tension responses and in the pA2 values for 4-DAMP assessed by carbachol contractures, in normal and obstructed bladder strips, indicates that m3 muscarinic receptors still play a predominant role in causing detrusor contractility in the obstructed bladder, as in the normal bladder.

Animals↗

PubMed1998

A wearable tremor-suppression orthosis.

The Viscous Beam is a wearable tremor-suppression orthosis that applies viscous resistance to motion of the wrist in flexion and extension. The orthosis reduces tremor amplitude and is small enough to be worn under the sleeve of a shirt. Hand and forearm cuffs couple the damper to the user. The cuffs permit full thumb and finger motion, wrist flexion and extension, and forearm pronation and supination. Damping is provided by a constrained-layer-damping (CLD) system, distinct in that it can damp large rotary deflections through a small bending radius. A bending-plate transmission linearly converts wrist extension/flexion to rectilinear translation within the damper. Bending deformation of two plates held a fixed distance apart within the transmission results in relative displacement along the lengths of the plates. A viscous fluid incorporated between the plates provides shear damping. Silicone fluids with viscosities as high as 10 million centistokes (cS) and shear layers as thin as 0.76 mm have been tested. With these parameter values, damping constants as high as 2.0x10(-3) N-m/(degrees/s) have been measured. This testing was conducted with strain rates as high as 4,580 degrees/s. The elastic stiffness of this beam was measured to be 4.1x10(-2) N-m/degrees.

Activities of Daily Living↗

PubMed2002

The role of M2 muscarinic receptor subtypes mediating contraction of the circular and longitudinal smooth muscle of the pig proximal urethra.

PURPOSE: We investigated the characterization of muscarinic receptor subtypes in the female pig urethra. MATERIALS AND METHODS: The affinities of muscarinic antagonists against carbachol responses were calculated in normal and cyclic adenosine monophosphate (cAMP) elevated tissues (contraction with KCl and relaxation with isoprenaline) using longitudinal and transverse strips of urethra. RESULTS: In displacement experiments with 1-quinuclidinyl [phenyl-4-3H] benzilate inhibitory constant (pKi) values of 4-diphenylacetoxyl-N-methyl-piperidine methiodide (DAMP) M3 selective antagonist) and methoctramine (M2 antagonist) indicated the presence of the M2 receptor. In functional studies contraction responses to carbachol were greater in longitudinal than in circular muscle. After cAMP elevation the contraction response increased in circular muscles to the level close to that of longitudinal muscles but did not change significantly in cAMP elevated longitudinal muscle. On normal circular tissues 4-DAMP had high mean affinity (mean apparent pKB value 9.3) but with a Schild slope of less than unity (0.76). Methoctramine competitively antagonized carbachol responses (mean affinity [pA2] value 6.9). On normal longitudinal tissues 4-DAMP and methoctramine competitively antagonized carbachol responses (mean pA2 9.0 and 6.2, respectively). After cAMP elevation in circular tissues mean pA2 values for 4-DAMP (8.7) were significantly lower (p = 0.0015), and those for methoctramine (7.3) were significantly higher (p = 0.0193) than in normal tissues. In longitudinal tissues the mean pA2 value for methoctramine (6.9) was significantly greater than in normal tissues (p <0.0001) but the value for 4-DAMP (8.8) did not alter. CONCLUSIONS: Pig urethra appears to have predominantly M2 muscarinic receptors. Contraction of the normal urethra appears to be predominantly mediated by M2 and M3 receptors in circular muscle but by M3 receptors in longitudinal muscle. After cAMP elevation a contribution to contraction of M2 receptors appeared to be demonstrated in the 2 tissues but the involvement of M2 receptors appeared greater in circular muscle.

Animals↗

PubMed1989

Effect in vivo of endogenous sexual hormones upon the liver mitochondrial function compared in male and female diabetic rats.

Chronic diabetes induced by the injection of streptozotocin in male and female albino adult rats provoked significant alteration of liver mitochondrial function 30 or 35 days after administration of the drug. Thus, we obtained mean values of respiratory control (RC) and state 3 (S3) with 3-hydroxybutyrate as substrate 40 or 50% lower than those of non-diabetic animals. With other substrates (malate-glutamate, succinate) the decrease of RC and S3 in the diabetic animals was 20% or 30% of the normal mean values. The osmotic damped oscillations of mitochondria were measured as another parameter of the organella function. It was assayed with valinomycin as K+ ionophore and succinate as substrate. In diabetic rats of both sexes we found a significant increase of the mean damping factor of these oscillatory variations compared with normal values. The above-mentioned results indicate a lesser elasticity and an impaired K+ transport of mitochondria across the inner membrane in diabetic animals. Both reported parameters, respiration and oscillatory variations of liver mitochondria, were measured in normal non-diabetic rats and in the groups of diabetic rats referred to as follows: 1) intact (male and female), 2) gonadectomized (male and female), 3) oophorectomized with restitution of 17 beta-estradiol. Ovariectomized diabetic rats showed a significant increase in the values of the RC and S3 of liver mitochondria compared with intact female diabetic animals. The withdrawal of the ovarian hormone in female diabetic rats significantly decreased the values of the damping factors of the oscillatory mechanism and they were similar to the normal. The restitution of 17 beta-estradiol to oophorectomized diabetic rats resulted in a decrease of liver mitochondrial respiration. The damping factor of liver mitochondria of the oophorectomized diabetic rats treated with the estrogen showed values significantly higher than those of female diabetic animals without the hormone and similar to the values of the intact diabetic female rats. Castration of male rats did not produce any effect upon the liver mitochondrial RC and S3 or upon the mean damping factor of the oscillatory variation either. Then the castration of male diabetic rats did not modify the mitochondrial function. In contrast, the oophorectomy of diabetic animals produced amelioration of mitochondrial respiration and oscillatory behavior. The conclusion is drawn that in female rats the circulating 17 beta-estradiol produced a pernicious effect upon liver mitochondrial function in the experimental diabetic state.

Animals↗

PubMed1979

Dynamic characteristics of the thorax connected with the heart action.

We determined the indices of local vibrations (resonance frequency, damping coefficient, stiffness constant, extinction time) and transfer function H(s) . 10(-6) for three somatotypes and three respiratory positions on 88 points of the thorax. The examinees were males (age 21 years). We found the resonance frequencies of 36.86--54.75 cps, damping coefficient (delta) 0.121--0.217. This means the damping is less than critical (delta = 1). We applied shocks (a force of 2 N) with a reflex hammer on 88 points of the thorax. The force diminished from the exciting place (say ictus) to the recording place (accelerometer on the sternum) from 2 to 0.2 N. The athletic type has the highest resonance frequency and stiffness constant; the leptosomic type has the highest damping; the longest extinction time belongs to the pyknic type. The pyknic type has also the highest value of the transfer function. The respiratory position (quiet respiration, Valsalva and Müller experiment) influences the values of the indices of local vibrations and of the transfer function. The influence is evident especially on the intercostal points: the transfer of the oscillations is alleviated at a higher stiffness of the thorax (Valsalva; the value of H(S) . 10(-6) rises from 7.00 to 9.39 sec2), it deteriorates at a small stiffness of the thorax (in Müller's experiment falls to 2.78 sec2). With the fall in the intrathoracic pressure the damping in the intercostal points decreases. On the basis of experiments the conclusion was made that a short testing of the thorax of an examinee will give the dynamic characteristics of the thorax (indices of local vibrations and transfer functions) of the individual. This procedure will alleviate the quantitative use of noninvasive mechanical methods in the assessment of the cardiovascular function.

Adult↗

PubMed1994

[Relationship between apo-protein in renal disease patients with diagnosis and TCM syndrome differentiation].

UNLABELLED: The relationship between the level of apo-protein in 132 renal disease patients with diagnosis and TCM Syndrome Differentiation was analysed. The serum apo-protein level of 132 patients group and 135 healthy adults group were monitored with radioimmunodiffusion assay. The patients were divided into three groups. Spleen Qi and Kidney Qi Deficiency (SQKQD), both Qi and Yin Deficiency (QYD), and the Liver Yin and Kidney Yin Deficiency (LYKYD) group. All patients were divided into with-Dampness and without-Dampness group according to their clinical symptoms and signs. Comparison was also made between different groups. RESULTS: Renal diseases including nephrotic syndrome, chronic nephritis, chronic renal failure and patients with SQKQD, QYD, LYKYD, the levels of apo-B and apo-B/apo-A-I were higher than that of normal (P < 0.01) in various degree, while the level of apo-A-I, was not changed or lower than the normal. In TCM Syndrome differentiation, apo-B and apo-B/apo-A-I in the SQKQD group were higher than those in QYD and LYKYD group (P < 0.05). Moreover, these two values in cases with Dampness were much higher than those without Dampness (P < 0.01). Therefore, it is important to treat this secondary abnormality of lipid metabolism for reducing the further deterioration of renal diseases. When primary renal disease was treated, elimination and removal the dampness might reduce the further damage of hyperlipidemia in renal diseases.

Adult↗

PubMed1994

The short-term compressive properties of adult human articular cartilage.

An apparatus and test method were developed to determine the elastic stiffness and damping coefficient of human cartilage in compression. An underdamped, counterbalanced beam applied a sudden compressive force to a full-thickness cylindrical specimen of articular cartilage. The initial oscillatory response decayed to steady state creep after approximately 10 cycles of oscillation. The results were consistent with a Voigt phenomenological model with linear stiffness and damping terms. Standard dynamics analysis of the transient oscillatory response enabled the elastic stiffness to be determined from the frequency and the damping coefficient to be derived from the logarithmic decrement of the decay of the oscillations. The relationship between the mechanical properties and structure of cartilage was determined by treating specimens with two specific proteolytic enzymes. Digestion and removal of proteoglycans alone with cathepsin D caused the damping coefficient to decrease with no change in elastic stiffness. The action of leukocyte elastase on collagen caused a decrease in both damping coefficient and elastic stiffness. It was concluded that the collagen fibrils in cartilage largely control the elastic response while the viscous response is controlled largely by the hydrated proteoglycans. The effects of cartilage thickness was also examined and found to be inversely proportional to the elastic stiffness. It is suggested that this method could be used to uncouple elastic and viscous properties of other viscoelastic materials.

Adult↗

PubMed1993

Immunoaffinity clean-up combined with 32P-postlabelling analysis of 1,N6-ethenoadenine and 3,N4-ethenocytosine in DNA.

Immunoaffinity gels able to bind 1,N6-ethenodeoxyadenosine 3'-monophosphate (3'-epsilon dAMP) and 3,N4-ethenodeoxycytidine 3'-monophosphate (3'-epsilon dCMP) were prepared. These gels retained their specific binding capacity for 3'-epsilon dAMP or 3'-epsilon dCMP in the presence of a large excess (> 2 mg per column) of unmodified 3'-deoxynucleotide monophosphates. 3'-epsilon dAMP and 3'-epsilon dCMP were 32P-postlabelled in the presence of [gamma-32P]ATP and T4 polynucleotide kinase to give either 3',5'-[5'-32P]-bisphosphates or 5'-[32P]monophosphates. 3',5'-[5'-32P]Bisphosphates were recovered from the labelling mixture by immunoprecipitation and quantitated by Cerenkov counting (method A). The detection limit of this procedure was 1 fmol with an efficiency of 80% for both ethenonucleotides. Alternatively, 5'-[32P]epsilon dAMP and 5'-[32P]epsilon dCMP were analysed by two-dimensional TLC on PEI cellulose and autoradiography (method B). The detection limit of method B was 50 amol of ethenonucleotide. Methods A and B are complementary and can quantify the formation and repair of 3'-epsilon dAMP and 3'-epsilon dCMP in DNA from rats exposed to a low level of vinyl chloride.

Adenine↗

PubMed2000

Risk factors for exacerbations and hospital admissions in asthma of early childhood.

Hospital admissions and readmissions for asthma in early childhood remain causes for concern. The purpose of this study was to identify predisposing risk factors related to asthma exacerbations and precursors of hospital admissions in young children. Subjects were patients with doctor-diagnosed asthma from a clinical registration study, aged 0-4 years, and followed up for 2 years. Data from histories and laboratory tests for atopic status at initial presentation, and the patient's condition at visits over the 2-year follow-up period were evaluated. Exacerbation was defined as increases in cough and/or wheeze and/or breathlessness, increase in beta(2)-agonist use, and a clinical need for a short course of oral corticosteroids. Age groups 0-1 year and 2-4 years, based on age at initial presentation, were analyzed separately. In the age group 0-1 year, 71/113 (63%) patients had at least one exacerbation, and 20 experienced recurrent exacerbations (>/=3). Predisposing risk factors for exacerbation were damp housing (odds ratio (OR) 7.6 (2. 0-28.6)) and colds (OR 3.6 (1.4-9.6)), and for recurrent exacerbations sensitization to inhalant allergens (Phadiatop(R)) (OR 8.1 (1.6-40.5)) and damp housing (OR 3.8 (1.1-12.8)). Hospital admissions were significantly associated with number of exacerbations. In the age group 2-4 years, 58/144 (40%) patients had at least one exacerbation, and 21 experienced recurrent exacerbations (>/=2). Predisposing risk factors for exacerbation were mean age at initial presentation (OR 0.92 (0.88-0.97)) and level of total IgE (OR 2.3 (1.4-3.9)), whereas for recurrent exacerbations no predictor variables were found. Hospital admissions were significantly associated with damp housing. Results from this study may facilitate recognition of young asthmatic patients at risk of (recurrent) exacerbations, and help to identify those in whom early intervention with anti-inflammatory therapy may be necessary. We also emphasize the importance of preventive measures in decreasing damp housing.

Anti-Inflammatory Agents↗

PubMed1982

A method of analyzing density-dependent vital rates with an application to the Gainj of Papua New Guinea.

A method of estimating age-specific coefficients of density-dependent variation in fertility and mortality is developed; the method is applicable to longitudinal data on population size and the number of births and deaths classified by age. Given a sufficiently large data set, it is possible to estimate both the sensitivity of each age class to density-dependent damping and the density effect of each age class on every age class in the population. Application of the method to government census data on the Gainj, a small tribal population from highland Papua New Guinea, shows that fertility is density-independent, but that mortality is at least partially density-dependent. This finding suggests that the size of the population is regulated by mortality rather than fertility. Individuals aged less than five years and greater than 50 years are particularly sensitive to density-dependent survival damping; individuals of adolescent and early reproductive age are not themselves damped, but appear to be responsible for the observed damping.

Adolescent↗

PubMed1976

Time delay in simple chemostat models.

The models of Monod and Williams, for the growth of unicellular organisms in chemostats, give strongly damped transients in the biomass and cell number when the flow rate of the chemostat is changed. A simple trick is used to incorporate time delay in these models while still allowing a conventional stability analysis. For long enough time delays the equilibrium point is unstable and limit cycles can be compared. Results obtained using Williams' model, with weakly damped transients as a result of using moderately long time delay, are compared with his data in which cell numbers show weak damping but biomass shows strong damping.

Cells, Cultured↗

PubMed1987

Catheter ablation: relationship of defibrillator waveform to the production of postshock ventricular tachyarrhythmias and myocardial damage.

The myocardial damage and arrhythmogenicity of percutaneous transcatheter shocks utilizing two different defibrillator waveforms (truncated exponential and damped sinusoidal) were compared. Ten dogs (33.7 +/- 3.6 kg) were studied. Five received left ventricular damped sinusoidal R-synchronous shocks during sinus rhythm and the other five received truncated exponential waveform shocks. Each dog received four energies (60, 120, 180, and 240 joules) randomly assigned to four left ventricular sites. The immediate postshock rhythms were recorded. Ventricular tachycardia occurred after 90% of the damped sinusoidal shocks compared to only 25% of the truncated exponential shocks (p less than 0.005). The animals were sacrificed 14 days later. Infarct size as determined by planimetry was not significantly different for the two waveforms. Thus intracavitary shocks utilizing a truncated exponential waveform are less arrhythmogenic than damped sinusoidal waveform shocks but produce similar morphologic changes and therefore may offer a significant safety advantage for catheter ablation procedures.

Animals↗

PubMed2007

Electrostatic energy in the effective fragment potential method: theory and application to benzene dimer.

Evaluation of the electrostatic energy within the effective fragment potential (EFP) method is presented. The performance of two variants of the distributed multipole analysis (DMA) together with two different models for estimating the charge penetration energies was studied using six homonuclear dimers. The importance of damping the higher order multipole terms, i.e. charge dipole, was also investigated. Damping corrections recover more than 70% of the charge penetration energy in all dimers, whereas higher order damping introduces only minor improvement. Electrostatic energies calculated by the numerical DMA are less accurate than those calculated by the analytic DMA. Analysis of bonding in the benzene dimer shows that EFP with inclusion of the electrostatic damping term performs very well compared to the high-level coupled cluster singles, doubles, and perturbative triples method. The largest error of 0.4 kcal/mol occurs for the sandwich dimer configuration. This error is about half the size of the corresponding error in second order perturbation theory. Thus, EFP in the current implementation is an accurate and computationally inexpensive method for calculating interaction energies in weakly bonded molecular complexes.

Algorithms↗

PubMed2007

Density functional theory augmented with an empirical dispersion term. Interaction energies and geometries of 80 noncovalent complexes compared with ab initio quantum mechanics calculations.

Standard density functional theory (DFT) is augmented with a damped empirical dispersion term. The damping function is optimized on a small, well balanced set of 22 van der Waals (vdW) complexes and verified on a validation set of 58 vdW complexes. Both sets contain biologically relevant molecules such as nucleic acid bases. Results are in remarkable agreement with reference high-level wave function data based on the CCSD(T) method. The geometries obtained by full gradient optimization are in very good agreement with the best available theoretical reference. In terms of the standard deviation and average errors, results including the empirical dispersion term are clearly superior to all pure density functionals investigated-B-LYP, B3-LYP, PBE, TPSS, TPSSh, and BH-LYP-and even surpass the MP2/cc-pVTZ method. The combination of empirical dispersion with the TPSS functional performs remarkably well. The most critical part of the empirical dispersion approach is the damping function. The damping parameters should be optimized for each density functional/basis set combination separately. To keep the method simple, we optimized mainly a single factor, s(R), scaling globally the vdW radii. For good results, a basis set of at least triple-zeta quality is required and diffuse functions are recommended, since the basis set superposition error seriously deteriorates the results. On average, the dispersion contribution to the interaction energy missing in the DFT functionals examined here is about 15 and 100% for the hydrogen-bonded and stacked complexes considered, respectively.

Hydrogen Bonding↗

PubMed1998

Two opposite signal transducing mechanisms regulate a G-protein-coupled guanylyl cyclase.

Membrane-bound guanylyl cyclase (GC) is regulated by muscarinic receptors (mAChRs). Carbamylcholine (CC) induces a "dual" biological response on GC activity. Thus, an activation is observed at 0.1 nM and a maximal response at 1 nM CC. However, at higher agonist concentration (> 100 nM), there is an agonist-dependent inhibition of GC. This CC dual response is affected by 4-DAMP and HDD (M3 antagonists), which produce a right-shift of the CC curve; the maximal CC dose response with 4-DAMP is more potent than that with HDD. Moreover, AFDX-DS (an M2 antagonist) increases basal activity and decreases the agonist-dependent inhibition. Neither the CC response nor the CC maximal dose responses are affected by pirenzepine (PZ, M1 antagonist). The agonist-dependent stimulation of GC activity is inhibited by 4-DAMP showing a -log IC50 = 8.4 +/- 0.4, while AFDX116 DS poorly inhibits such activity with a -log IC50 = 5.0 +/- 0.2. The agonist-independent (basal) GC activity also was inhibited by 4-DAMP, in a dose-dependent manner, with an IC50 = 8.5 +/- 0.2. Nonetheless, other muscarinic antagonists (PZ and HDD) were not able to inhibit this basal GC. Pertussis toxin treatment produces a complete blockade of the agonist-dependent inhibition of GC with a full expression of the agonist-dependent activation of membrane-bound GC. These results indicate that membrane-bound GC is regulated by muscarinic agents through two opposite signaling pathways; one involves the activation of GC via an M3 mAchR coupled to a PTX-insensitive G protein, while the GC inhibition is mediated through a PTX-sensitive Gi/o protein possibly coupled to an M2 mAChR.

Animals↗

PubMed1995

Adverse effects of the indoor environment on respiratory health in primary school children.

Exposure to various factors from the indoor environment on respiratory health of 470 Dutch primary school children was studied. We investigated which of the factors, such as home dampness, passive smoking, unvented kitchen geysers, or pets, affected children's respiratory health the most, and whether airway sensitivity to these indoors exposures differed between boys and girls. Information on respiratory morbidity and characteristics of the housing was obtained by a written questionnaire, completed by the parents of the children. Lung function of the children was measured at school, by forced oscillation technique (FOT) and spirometry. In boys, all investigated lung function parameters were significantly affected by exposure to passive smoking during the child's entire life. Although mostly nonsignificant, all of the reported asthma-like symptoms were related especially to maternal smoking, with a trend of a dose-response relationship. Furthermore, damp stains (P < 0.05) and mold growth (ns) were associated with chronic cough and with small but significant impairments in part of the lung function parameters. No consistent patterns were observed with unvented kitchen geysers and pets. Although passive smoking (cumulative dose) in girls was also associated with lung function impairments, the effects were smaller than those in boys and not all significant. Associations between the asthma-like symptoms and the dose of maternal and paternal smoking also were less consistent. Furthermore, no associations were found with the dampness indicators and with pets, but unvented kitchen geysers were significantly related to impairments in some of the impedance indices. This study shows detrimental effects of several indoor factors on the prevalence of chronic respiratory symptoms and lung function in children, which are most pronounced for passive smoking, and somewhat less pronounced for dampness and the presence of unvented kitchen geysers. Airway sensitivity to these exposures appeared to be higher in boys than in girls.

Air Pollution, Indoor↗