Repeated stress reduces mucociliary clearance in animals with chronic allergic airway inflammation

We evaluated if repeated stress modulates mucociliary clearance and inflammatory responses in airways of guinea pigs (GP) with chronic inflammation. The GP received seven exposures of ovalbumin or saline 0.9%. After 4th inhalation, animals were submitted to repeated forced swim stressor protocol (5×/week/2 weeks). After 7th inhalation, GP were anesthetized. We measured transepithelial potential difference, ciliary beat frequency, mucociliary transport, contact angle, cough transportability and serum cortisol levels. Lungs and adrenals were removed, weighed and analyzed by morphometry. Ovalbumin-exposed animals submitted to repeated stress had a reduction in mucociliary transport, and an increase on serum cortisol, adrenals weight, mucus wettability and adhesivity, positive acid mucus area and IL-4 positive cells in airway compared to non-stressed ovalbumin-exposed animals (p < 0.05). There were no effects on eosinophilic recruitment and IL-13 positive cells. Repeated stress reduces mucociliary clearance due to mucus rheological-property alterations, increasing acid mucus and its wettability and adhesivity. These effects seem to be associated with IL-4 activation.     

Bronchial mucociliary clearance in chronic bronchitics (author's transl)]

Bronchial mucociliary clearance is analysed in 13 clinically stable patients with chronic bronchitis in comparison with 7 normal non smokers by measuring the rate of removal of inhaled monodispersed particles of resin (diameter: 8.1 +/- 3.5 micrometer) tagged with 99mTc. Particles delivered with a high insufflation rate are uniformly deposited on proximal airways. The pattern of distribution is comparable in all the subjects studied. In normal non smokers, the percentage of bronchial radioactivity cleared 1 h after the inhalation was 34 +/- 11.2 percent. The patients may be divided into 2 groups: Group 1 (n = 6) is characterized by a mucociliary clearance similar to the normals while group 2 (n = 7) shows a low mucociliary transport rate (decrease of bronchial radioactivity after 4 h less than 10 percent).     

The effects on mucociliary clearance of prednisone associated with bronchial section

OBJECTIVE:

Infections have been and remain the major cause of morbidity and mortality after lung transplantation. Because mucociliary clearance plays an important role in human defense mechanisms, the influence of drugs on the mucociliary epithelium of patients undergoing lung transplantation must be examined. Prednisone is the most important corticosteroid used after lung transplantation. The aim of this study was to evaluate the effects of bronchial transection and prednisone therapy on mucociliary clearance.

METHODS:

A total of 120 rats were assigned to 4 groups according to surgical procedure or drug therapy: prednisone therapy (1.25 mg/kg/day); bronchial section and anastomosis + prednisone therapy (1.25 mg/kg/day); bronchial section + saline solution (2 ml/day); and saline solution (2 ml/day). After 7, 15, or 30 days, the animals were sacrificed, and the lungs were removed from the thoracic cavity. The in situ mucociliary transport velocity, ciliary beat frequency and in vitro mucus transportability were evaluated.

RESULTS:

Animals undergoing bronchial section surgery and anastomosis had a significant decrease in the ciliary beat frequency and mucociliary transport velocity 7 and 15 days after surgery (p<0.001). These parameters were normalized 30 days after the surgical procedure. Prednisone improved mucous transportability in the animals undergoing bronchial section and anastomosis at 15 and 30 days (p<0.05).

CONCLUSION:

Bronchial section and anastomosis decrease mucociliary clearance in the early postoperative period. Prednisone therapy improves mucus transportability in animals undergoing bronchial section and anastomosis.     

Specific skin tests in subjects with chronic bronchitis exposed to pigeons

We have studied the diagnostic reliability of the specific skin tests done in 30 subjects who presented with chronic bronchitis (CB) as the only clinical manifestation related to exposure to pigeons and in 21 subjects with CB and known risk factors. Additionally, two control groups were included (24 asymptomatic subjects exposed and sensitized to pigeons and 10 subjects not exposed and not sensitized to pigeons). The skin prick tests with pigeon scrum were negative in all the subjects tested. The intradermal skin tests showed an immediate positive reaction in 16 of the 30 CB-affected patients and in six of the control group of exposed asymptomatic subjects (chi square: 3.376) ( P <0.1; nearly significant); after 6 h, a positive reaction was recorded in 14 of the CB-affected patients and in three subjects of the control group (chi square: 5.187) ( P < 0.005). A delayed reaction was seen in 10/30 CB patients and in only three of the 24 subjects of the control group (chi square: 2.218) (nonsignificant). In the group of the 21 CB patients with known risk factors and not sensitized to pigeons, only two patients showed immediate skin reactivity; the remaining readings were negative. Lastly, in the control group of 10 unexposed, nonsensitized subjects, the intradermal skin tests in the different readings were negative. Our results show that although the skin tests with pigeon serum have low sensitivity, they can be a useful supplement in distinguishing cases of CB attributable to chronic pigeon exposure from those cases attributable to another cause, especially in the consideration of immediate and late readings.     

Comparison of forced oscillometry and forced expirations for measuring dose-related responses to inhaled methacholine in asthmatic children

The forced oscillation technique (FOT) is a lung function method which is applicable from the age of 2.5 years onwards, because only passive co-operation is needed. We used the method as described by Làndsér et al. The aim of this study was to compare indices of bronchial responsiveness obtained by FOT (Rrs6, Rrs, dRrs/df, Xrs), with indices derived from maximal and partial expiratory flow-volume curves (MEFV25, PEFV25, FEV1). Bronchial responsiveness was assessed by methacholine inhalation. Threshold dose (TD), i.e. the dose which caused a 2 SD change from baseline lung function, and provocation dose (PD), i.e. the dose which caused a 20% fall in FEV1, a 40% fall in MEFV25 and PEFV25 and a 40% increase in Rrs and Rrs6, were determined. We found that the indices derived from forced oscillometry compared well to those from maximal and partial flow-volume curves. PD20 FEV1 and PD40 Rrs6 were highly correlated (r = 0.84). TD appeared to be as good as PD to measure bronchial responsiveness and is preferred to PD because of the lower dose needed and limited bronchoconstriction obtained.     

Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression.

The chronic fatigue syndrome (CFS) is characterized by severe persistent fatigue and neuropsychiatric symptoms. It has been proposed that the abnormalities in cell-mediated immunity which have been documented in patients with CFS may be attributable to a clinical depression, prevalent in patients with this disorder. Cell-mediated immune status was evaluated in patients with carefully defined CFS and compared with that of matched subjects with major depression (non-melancholic, non-psychotic) as well as healthy control subjects. Patients with CFS demonstrated impaired lymphocyte responses to phytohaemagglutinin (PHA) stimulation, and reduced or absent delayed-type hypersensitivity (DTH) skin responses when compared either with subjects with major depression or with healthy control subjects (P less than 0.05 for each analysis). Although depression is common in patients with CFS, the disturbances of cell-mediated immunity in this disorder differ in prevalence and magnitude from those associated with major depression. These observations strengthen the likelihood of a direct relationship between abnormal cell-mediated immunity and the etiology of CFS.     

The effect of ethanol on fat storage in healthy subjects.

BACKGROUND. Ethanol can account for up to 10 percent of the energy intake of persons who consume moderate amounts of ethanol. Its effect on energy metabolism, however, is not known. METHODS. We studied the effect of ethanol on 24-hour substrate-oxidation rates in eight normal men during two 48-hour sessions in an indirect-calorimetry chamber. In each session, the first 24 hours served as the control period. On the second day of one session, an additional 25 percent of the total energy requirement was added as ethanol (mean [+/- SD], 96 +/- 4 g per day); during the other session, 25 percent of the total energy requirement was replaced by ethanol, which was isocalorically substituted for lipids and carbohydrates. RESULTS. Both the addition of ethanol and the isocaloric substitution of ethanol for other foods reduced 24-hour lipid oxidation. The respective mean (+/- SE) decreases were 49.4 +/- 6.7 and 44.1 +/- 9.3 g per day (i.e., reductions of 36 +/- 3 percent and 31 +/- 7 percent from the oxidation rate during the control day; P less than 0.001 and P less than 0.0025). This effect occurred only during the daytime period (8:30 a.m. to 11:30 p.m.), when ethanol was consumed and metabolized. Neither the addition of ethanol to the diet nor the isocaloric substitution of ethanol for other foods significantly altered the oxidation of carbohydrate or protein. Both regimens including ethanol produced an increase in 24-hour energy expenditure (7 +/- 1 percent with the addition of ethanol, P less than 0.001; 4 +/- 1 percent with the substitution of ethanol for other energy sources, P less than 0.025). CONCLUSIONS. Ethanol, either added to the diet or substituted for other foods, increases 24-hour energy expenditure and decreases lipid oxidation. Habitual consumption of ethanol in excess of energy needs probably favors lipid storage and weight gain.     

The effect on erythropoiesis of serum from healthy and anemic subjects

Summary A subcutaneous injection of 3 ml of serum of patients suffering from acute posthemorrhagic anemia and from pernicious anemia provokes an increase in the number of reticulocytes in healthy rabbits. Not only is there a peripheral reticulocytosis, but there is also an increase in the number of reticulocytes and erythroblasts in the bone marrow.The serum of some patients suffering from iron deficiency anemia possesses the same property, but the effect occurs less regularly than in the groups mentioned previously.Some of the healthy persons has no effect on the number of reticulocytes. Possibly there is an increased production of erythropoetins in some forms of anemia.Presented by Active Member of the AMN SSSR M. D. Tushinskii     

Adenosine triphosphate in exhaled breath condensate of healthy subjects and patients with chronic obstructive pulmonary disease

OBJECTIVES: The effect of hypoxic relapse of chronic obstructive pulmonary disease (COPD) on lung adenosine triphosphate (ATP) concentration was studied measuring ATP in exhaled breath condensate (EBC). SUBJECTS: Thirty COPD patients with severe exacerbation, thirteen healthy non-smokers and thirteen healthy smokers. METHODS: ATP was detected using a luciferin-luciferase assay, dilution of airway droplets in EBC was assessed measuring sample conductivity. RESULTS: ATP concentrations were similar in COPD patients, non-smoking and smoking healthy individuals (141 +/- 44, 115 +/- 21 and 90 +/- 15 pM; p = 0.66). After treatment oxygenation of COPD patients improved (6.85 +/- 1.29 kPa vs 8.20 +/- 1.28 kPa, p <0.001), but EBC ATP concentration was similar to that of admission (p = 0.84). There was no correlation between EBC ATP concentration and airway droplet dilution. CONCLUSION: ATP detected in EBC indicates the presence of ATP in airway lining fluid. Lack of difference in ATP concentration between health and COPD suggests that airway ATP level is under complex control of multiple factors.     

Effect of atropine on tracheal mucociliary clearance and bacterial counts

The purpose of this study was to determine if atropine, which has been shown to alter mucosal function, prolongs the persistence of inhaled bacteria in the trachea. In conscious sheep, bacterial counts in the trachea were determined by quantitative sterile brush cultures obtained before and serially after a controlled inhalation challenge with an aerosolized solution containing P. hemolytica (10(8) CFU X ml-1). The same animals were studied on two days, once without (control day) and once before and during intramuscular administration of 0.2 mg X kg-1 atropine sulfate at hourly intervals for up to 10 h (atropine day). On the control and atropine days, bacterial counts were zero before, and between 5 X 10(5) and 1.6 X 10(7) CFU X ml-1 immediately after inhalation of P. hemolytica. During the first 2 h after challenge, there was a similar semilogarithmic decline in bacterial counts on the control and atropine days despite the fact that mean tracheal mucociliary transport velocity remained unchanged on the control day, and ranged between 32% and 62% of baseline (p less than 0.05) during the 6-10 h post-drug observation period on the atropine day. However, the time to achieve sterility on the control day was less than or equal to 8 h in all animals, and greater than or equal to 8 h on the atropine day. We conclude that atropine prolongs the persistence of viable bacteria in the trachea. This effect of atropine may be related to an impairment of mucociliary clearance or to other alterations in mucosal function.     

The effect of baclofen and diazepam on motor skill acquisition in healthy subjects

Antispastic medication is often used in the clinic together with physiotherapy. However, some of the antispastic drugs, e.g., baclofen and diazepam, may influence the plastic mechanisms that are necessary for motor learning and hence efficient physiotherapy. In the present study, we consequently investigated the influence of baclofen and diazepam on acquisition of a visuomotor skill. The study was designed as a semi-randomized, double-blinded, placebo-controlled, crossover study in 16 healthy human subjects. The motor skill task required the subjects to match a given force trajectory by increasing or decreasing ankle dorsiflexor torque. Subjects trained for a total of 30 min. Transcranial magnetic stimulation of the primary motor cortex leg area was applied to elicit motor evoked potentials in the anterior tibial muscle (TA). Coupling between populations of TA motor units was calculated in the frequency (coherence) domain during isometric dorsiflexion. Subjects receiving placebo showed statistically significant improvement in motor performance (q = 34.1, P = 0.014) accompanied by a statistically significant reduction in intramuscular coherence. Subjects receiving baclofen and diazepam conversely showed no progression in motor performance (P > 0.05), and the training was not accompanied by a decrease in intramuscular coherence. TA motor evoked potentials had significantly lower threshold following the training in the placebo group, whereas this was not the case in the treatment groups. These data indicate that diazepam and baclofen interfere with the acquisition of a motor skill by disrupting some of the neuroplastic changes that are involved in improved motor performance. This suggests that antispastic treatment should be used with caution in subjects receiving concomitant physiotherapy.     

Nonlinear analysis of heart rate variability of healthy subjects and patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of the causes of mortality worldwide with an increasing prevalence. Heart rate variability (HRV) reflects the regulation mechanism of the cardiac activity by the autonomic nervous system. The assessment of HRV by using nonlinear methods is more sensitive for the detection of complexity when compared to linear methods. This study aims to get information about the autonomic dysfunction occurred in patients with COPD by analysing the complexity of HRV. Electrocardiogram signals recorded from healthy subjects, patients with moderate COPD and severe COPD (eight subjects per group) were analysed. The HRV signals were acquired from ECG signals. Signals were reconstructed in the phase space and largest Lyapunov exponent (LLE), correlation dimension, Hurst exponent and approximate entropy (ApEn) values were calculated. It has seen that for the patients with COPD LLE, correlation dimension, Hurst exponent and ApEn values were less than control group. According to this, HRV complexity decreases in the presence of COPD. However, there is no significant difference between COPD groups and the severity of COPD has no effect on the chaoticity of the system. The results revealed that autonomic dysfunction occurred in patients with COPD is associated with reduced HRV complexity.     

The effect of bright light exposure on pupillary fluctuations in healthy subjects

BACKGROUND: Light therapy is thought to be the first choice treatment of winter depression. However, its way of action is poorly understood. In order to find a solid effect of bright artificial light, we studied its possible alerting action through the spontaneous fluctuations of the pupil, considered to be an objective measurement of vigilance. METHODS: Pupillary fluctuations of 10 healthy subjects (mean age: 22+/-1 S.D. years) were measured for 60 s before and 15 min after 0.5 h, 10000-lux light exposure. The cumulative change in pupil size, characterised by the pupillary unrest index (PUI) decreased at each subject, and this decrease was in average 35+/-4.4% S.E.M. The average pupillary diameters were unchanged (101+/-2.2% S.E.M.). This analysis revealed that the slow components of the pupillary fluctuations also decreased considerably. LIMITATIONS: There was no dim light or other placebo control of the light treatment. CONCLUSIONS: Bright light exposure significantly influenced the pupillary fluctuations. We suppose that bright light exposure increases the level of alertness, and this could be a possible way by which bright artificial light exerts a beneficial effect also in affective disorders.     

Assessment of cortisol response with low-dose and high-dose ACTH in patients with chronic fatigue syndrome and healthy comparison subjects

A reduced secretion of cortisol has been proposed as a possible explanation of the symptoms in chronic fatigue syndrome. However, the evidence of hypocortisolism in chronic fatigue syndrome is conflicting. In order to simultaneously assess possible alterations in adrenocortical sensitivity and secretory adrenal reserve, the authors administered both low-dose and high-dose ACTH to a group of 18 chronic fatigue syndrome patients and 18 age- and gender-matched healthy comparison subjects. No response differences for salivary and plasma cortisol were detectable after administration of either low-dose or high-dose ACTH, indicating that primary adrenal insufficiency is unlikely to play a significant role in the etiology of chronic fatigue syndrome.     

The effect of ACTH on the plasma level of non-esterified fatty acids in healthy subjects and in diabetic patients

Summary Following an intramuscular injection of ACTH to a group of healthy subjects a decrease was observed in the level of non-esterified fatty acids of the plasma, replaced by an increase in their concentration, whereas in a group of diabetes patients only a stage of decrease was observed under identical conditions. The most marked decrease in the concentration of non-esterified fatty acids in the plasma was noted in cases with a higher initial level. No quantitative relationship could be established between the decrease in the concentration of non-esterified fatty acids in the plasma was noted in cases with a higher initial level. No quantitative relationship could be established between the decrease in the concentration of non-esterified fatty acids and the increase in the amount of free 11-hydroxycorticosteroids of the plasma following an ACTH injection. The results of observations evidence the dependence of the ACTH administration effect on the initial condition of the organism, and agree with the hypothesis of a direct, extraadrenal mechanism of ACTH action on the level of non-esterified fatty acids of the plasma.(Presented by Academician V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 59, No. 5, pp. 48–51, May, 1965     

96例慢性喘息型支气管炎的治疗体会

喘息型慢性支气管炎是临床内科的一种多发病、常见病,严重威胁着人们的健康.此类患者多有过敏史,临床上以喘息为特征,极易并发阻塞性肺气肿、肺心病,对患者日常生活和工作造成严重影响.本病治疗的目标是缓解咳嗽、喘息和呼吸困难症状[1-2].硝苯地平和氨茶碱都具有较强的平滑肌松弛作用,抑制组织胺等炎性递质的释放,增加膈肌的张力和耐力,从而改善患者的呼吸功能.我院于2002至2007年应用硝苯地平、氨茶碱加低流量持续性吸氧治疗该病96例,收到满意疗效.现报告如下.     

Uricosuric effect of irtemazole in healthy subjects

Summary Following a single dose of 50 mg irtemazole per os, plasma uric acid levels decreased after 1 h and fell to 53.5% of the original value within 6–12 h. Renal uric acid excretion increased up to 66 mg/h 30 min after drug application and reached its maximum of 151 mg/h 30 min later. Uric acid clearance also increased after 30 min and reached its maximum of 56 ml/min after 60 min.The response of the kidney to irtemazole is faster than to benzbromarone or probenecid. Lowering of plasma uric acid has a shorter-lasting effect than benzbromarone or probenecid. At 24 h after the application of 50 mg irtemazole the decrease of the plasma uric acid was between 15.4% and 30.0%, or 24.7% on average. Three days after the application the basic plasma uric acid levels were reached again.