The effect of nitroglycerine medication on the arterial oxygen pressure in obstructive lung disease

Nitroglycerine gains increasing interest because of its favourable hemodynamic effects in patients with left heart failure, especially in those with coronary heart disease. The drug-induced vasodilatation and lowering of pulmonary arterial pressure, is followed by a redistribution of lung perfusion which occasionally may be deletarious. It is shown that in patients with obstructive lung disease, a significant drop in arterial oxygen tension may be observed. This could be due to increased perfusion of the lung, without a concommitant augmentation of ventilation, which results in an increase of right to left-shunt.     

Relationship between serum immunoglobulin, inhalation bronchial challenges and skin tests in severe asthmatics

The relationship among inhalation bronchial challenge tests, skin tests, total serum immunoglobulin E, A, M, and G values were investigated. Positive correlation between the results of the inhalation bronchial challenges and IgG and negative correlation between the value of IgG and IgA were found but no other correlations.     

Misoprostol has no favorable effect on bronchial hyperresponsiveness in mild asthmatics

Misoprostol, a synthetic prostaglandin E1 analogue, has been reported to have antibronchoconstricive and antiinflammatory effects in animal studies. We investigated the effect of misoprostol on FEV1 and bronchial hyperresponsiveness (BHR) to histamine in mildly asthmatics. 14 mildly asthmatic patients were given 400 mg/day oral misoprostol. Four patients had to left the study either due to the side effects. The remaining 10 patients (all women and mean age was 33.2 +/- 3.3) underwent the histamine challenge test before and after the treatment with misoprostol. Mean values of FEV1 obtained before and after the treatment were as follows respectively: 2.79 +/- 0.17 L; 2.78 +/- 0.18 L. Mean log PC20 values were as follows respectively: 0.60 +/- 0.23 mg/ml; 0.60 +/- 0.14 mg/ml. There was no difference either in FEV1 and log PC20 values before and after the treatment with misoprostol (p > 0.05). As a result administered misoprostol has no favorable effect on expiratory flow rates and BHR in asthmatic patients.     

Anticoagulative effect of nitric oxide inhalation in ARDS

Some studies have suggested that nitric oxide (NO) may cause platelet dysfunction. We present an ARDS patient who need this treatment, with a transient alteration of platelet function and a significant prolongation of bleeding time.     

Suppressive effect of corticosteroids on the gene expression of interleukin-5 and eosinophil activation in asthmatics

Although cortico steroids are effective anti-inflammatory agents in ameliorating asthma symptoms and bronchial hperreactivity, their mechanism of action is unknown. Interleukin (IL)-5 is known to play a key role in regulating eosinophil proliferation and activation. Therefore, we examined the changes of IL-5 mRNA expressions in PBMC semi-quantitatively with RT-PCR as well as serum ECP levels and MCH-PC20 values in asthmatics before and after being treated with corticosteroids. The results revealed that there were significant decrease in the level of IL-5 mRNA and serum ECP concentration after therapy (P < 0.05) and there was remarkable improvement in the values of MCH-PC20 and FEV1% (P < 0.05). It was also found that the changes of serum ECP levels or MCH-PC20 values were accompanied by a reduction in IL-5 mRNA expression (r = 0.5426 or 0.4857, P < 0.05). These results suggested that the therapeutic effects of corticosteroids in asthma may result from modulation of IL-5 gene expression with consequent inhibition of eosinophil activation.     

Prostaglandin H synthase 1 and 2 immunoreactivities in the bronchial mucosa of asthmatics

Prostaglandin H synthases or cyclooxygenases 1 (PGHS-1) and 2 (PGHS-2) catalyze the conversion of arachidonic acid to prostaglandin endoperoxides, leading to the formation of prostaglandin and thromboxane mediators of inflammation. The expression of these enzymes in the respiratory epithelium has not been determined, although they may be relevant to the pathophysiology of inflammatory disorders such as asthma and chronic bronchitis (CB). We studied PGHS-1 and PGHS-2 immunoreactivity in bronchial biopsies obtained from 22 patients with chronic stable asthma, seven patients with CB, and 12 normal subjects. Both types of PGHS were mainly expressed in the epithelium (basal and ciliated cells), and PGHS-1 and PGHS-2 were found in 21 of 41 and 34 of 41 biopsies, respectively. We did not find any differences in PGHS expression between the patient populations. There were no correlations between any of the clinical parameters studied or the pathologic patterns and the presence and characteristics of the PGHS immunoreactivities. Thus, both PGHS enzymes are expressed in normal human respiratory epithelium and are not quantitatively upregulated in the main bronchi in stable asthma and CB.     

MnO_2掺杂对NiZn铁氧体磁性能的影响

采用传统陶瓷工艺制备了MnO2掺杂Ni0.88Zn0.12Fe1.98O4铁氧体材料。实验发现,较高的烧结温度有助于NiZn铁氧体磁导率的提高,但过高和过低烧结温度都不利于材料品质因数的提高,从降低损耗的角度考虑,最佳烧结温度为1220℃。当NiZn铁氧体中MnO2掺杂量为1.5%时,铁氧体晶粒生长均匀,平均晶粒尺寸适中,能获得最高的品质因数,过低或过高的掺杂量都不利于损耗的降低。铁氧体饱和磁感应强度随MnO2掺杂量的增多先上升,后下降,但总体的变化程度都不大。而矫顽力则随掺杂量的增多持续下降。相关的影响机制在文中作了详细的讨论。     

Demonstration and isolation of the hybrid hemoglobins alpha 2 A beta A beta C and alpha 2 A beta S beta C

The corss-linking reagent p,p'-difluoro-m,m'-dinitrodiphenylsulfone has been used to fix in the tetramer form the various species of hemoglobin present in mixtures of hemoglobin A and hemoglobin C and of hemoglobin S and hemoglobin C. Following reaction, the presence of the hybrid hemoglobins alpha 2 A beta A beta C and alpha 2 A beta S beta C in these hemoglobin mixtures was demonstrated electrophoretically and the hybrids were isolated by ion-exchange chromatography. The identity of the alpha 2 A beta A beta C hybrid was further verified by peptide analysis. The success in cross-linking alpha 2 A beta 2 C, alpha 2 A beta A beta C, and alpha 2 A beta S beta C with p,p'-difluoro-m,m'-dinitrodiphenylsulfone shows that the distance between the alpha chain amino terminals in solution for these hemoglobin species is the same as in normal hemoglobin.     

CeO_2添加剂对Cr_2O_3涂层组织和抗热震性的影响

本文在 Cr2 O3陶瓷材料中添加不同含量的 Ce O2 ,探讨了 Ce O2 对等离子喷涂 Cr2 O3涂层组织和抗热震性的影响。研究结果表明 ,加入 3.0 % Ce O2 可降低涂层中的孔隙率和空洞尺寸 ,减少涂层内应力在孔隙边缘的应力集中 ,从而提高 Cr2 O3涂层的抗热震性。陶瓷涂层的热震失效是由于涂层在循环加热和冷却过程中 ,涂层内产生循环热应力 ,导致涂层发生热疲劳失效     

Additive anticonvulsant effect of flunarizine and sodium valproate on electroshock and chemoshock induced seizures in mice

Calcium influx through the TRP and TRPL light-activated channels triggers a complex regulatory hierarchy resulting in positive and negative feedback regulation of the phototransduction cascade. Recent studies have begun to elucidate the function of TRP and TRPL in vivo, and to examine their relationship to intracellular calcium changes during the light response.     

Additive effect of mifepristone and tamoxifen on apoptotic pathways in MCF-7 human breast cancer cells

MCF-7 cells growing in culture were used to study the mechanism of the antiproliferative activity of the antiprogestin mifepristone, as compared with the antiestrogen 4-hydroxytamoxifen or the combination of both. These steroid antagonists induced a significant time- and dose-dependent cell growth inhibition (cytotoxicity). This inhibition of cell survival was associated with a significant increase in DNA fragmentation (apoptosis), downregulation of bcl2, and induction of TGFbeta1 protein. Abrogation of the mifepristone- and/or 4-hydroxytamoxifen-induced cytotoxicity by TGFbeta1 neutralizing antibody confirms the correlation between induction of active TGFbeta1 and subsequent cell death. The effect of a combination of mifepristone and 4-hydroxytamoxifen on cell growth inhibition, on the increase in DNA fragmentation, bcl2 downregulation, and induction of TGFbeta1 protein was additive and significantly different (P < 0.05) from the effect of monotherapy. A translocation of protein kinase C (PKC) activity from the soluble to the particulate and/or nuclear fraction appeared to be also additive in cells treated with a combination of both 4-hydroxytamoxifen and mifepristone. These results suggest that the mechanism of the additive antiproliferative activity of mifepristone and tamoxifen could be explained at least in part by an additive induction of apoptosis in both estrogen and progesterone receptor positive MCF-7 breast cancer cells. A bcl2 downregulation, the PKC transduction pathway, and TGFbeta1 expression seem to be involved in this additive mechanism of action. Our data further suggest that a combination of an antiprogestin with tamoxifen may be more effective than tamoxifen monotherapy in the management of human breast cancer.     

Additive effect of beraprost on pulmonary vasodilation by inhaled nitric oxide in children with pulmonary hypertension

Using a prospective audit, we have evaluated the efficacy of an integrated autotransfusion regimen which comprised predepositing and intra- and postoperative blood salvage in major orthopaedic surgery. We examined prospectively the records of 1785 patients (1198 females, 5867 males, mean age 62 (range 16-90) yr, preoperative haemoglobin concentration 13.4 (SD 1.4) g dl-1) undergoing total hip arthroplasty (THA, 1229 patients), THA after removal of internal fixation devices (RFD + THA, 18 patients), total knee arthroplasty (TKA, 263 patients), revision surgery of the hip (HR cup + stem revision, 197 patients; cup revision, 53 patients; stem revision, 16 patients) and total knee revision (TKR, nine patients). We estimated that the number of predonations (MSBOS = maximum surgery blood order schedule) was 2 u. for THA, TKA and TKR, and 3 u. for partial or total hip revision and total hip arthroplasty with fixation removal. We found that it was possible to obtain the MSBOS in 1597 patients (89.5%). Homologous red blood cell (HRBC) transfusions were carried out in 131 patients (7.3%). We found that the need to use HRBC was significantly associated with failure to meet the number of MSBOS, female sex, lower preoperative haemoglobin concentration, use of calcium heparin for antithrombosis prophylaxis, more extensive surgery, higher ASA rating and co-existing diseases such as coronary artery disease.     

Polymorphism of the beta2-adrenoceptor and the response to long-term beta2-agonist therapy in asthma

DNA-based diagnosis of haemophilia A has previously been carried out by linkage analysis using two highly informative markers, Hind III RFLP and St14 VNTR, for affected Turkish families. In the present study the number and frequency of the microsatellite alleles at introns 13 and 22 in the factor VIII (FVIII) gene were analysed in order to increase the rate of informative females and accuracy of linkage analysis. Six alleles were observed at both loci. The two most frequent alleles of each locus were the same as the two common alleles found in Anglo-Americans. The comparison of heterozygosity of both microsatellite loci showed that the Turkish population is slightly less polymorphic than Anglo-Americans but more polymorphic than Chinese, Slavs and Uzbekians. The additional use of the two microsatellite repeat polymorphisms with the previously established informative markers has been accepted as the most effective strategy in DNA diagnosis by linkage analysis for the assessment of haemophilia A carriers and affected fetuses in the Turkish population. The modifications adopted in this study for the multiplex PCR analysis of the microsatellite repeat polymorphism eliminated the use of radioactivity and sequencing gels, reducing cost and labour.     

Peripheral plasma determinations of prostaglandin E in asthmatics

Prostaglandins, unsaturated fatty acid derivatives with diversified pharmacologic activity, have recently been implicated in the pathophysiology of reversible airway disease. This study attempted to elucidate baseline prostaglandin E (PGE) plasma levels in asthmatics and the change in these levels after stimulation by a beta-adrenergic agent. Fourteen stable, ambulant patients with reversible airway disease and 28 nonatopic control subjects were studied. All had baseline PGE levels performed. The asthmatics were asked to abstain from all medication for 10 hr prior to evaluation. After baseline evaluation consisting of plasma PGE determination, pulmonary function test, blood pressure, and heart rate, 375 mug of aerosolized terbutaline sulfate was administered to 8 of the asthmatics plus 4 of the nonatopic control subjects; the above measurements were repeated at 15, 30, and 60 min after administration. There was a statistically significant difference in baseline plasma PGE levels between the asthmatics (PGE = 432 +/- 81) and the nonatopic control subjects (PGE = 89 +/- 9) (p less than 0.002). Following terbutaline administration, there was no significant change observed in PGE levels in asthmatic or in control individuals (asthmatics: 0 min, 570, 15 min, 513, 30 min, 514, 60 min, 608; normal subjects: 0 min, 138, 15 min, 137, 30 min, 143, 60 min, 214). In summary, we observed a significant difference in baseline PGE levels between asthmatic and nonatopic control persons. No change, however, was noted in PGE levels after beta-adrenergic receptor stimulation. This observation is consistent with the current hypothesis that beta-adrenergic agents act independently of prostaglandins to increase adenyl cyclase and modify bronchiole smooth muscle tone.     

Antibodies against beta1 and beta2 adrenergic receptors in myasthenia gravis

With ageing the membrane/soluble form ratio of membrane-boundenzymes increases especially in the ileum and that of peptidases changes rather insignificantly in both portions of the rat small intestine. The soluble forms are supposed to take part in assimilation of food substrates penetrating enterocytes in an unsplit form due to an enhanced permeability of the membranes, particularly those of the ileum.     

Effects of prolonged CO2 inhalation on shivering thermogenesis during cold-water immersion

We investigated the effect of prolonged hypercapnia on human thermoregulation during immersion of seven male subjects in a 15 degrees C water bath until their esophageal temperature dropped to 35 degrees C or until 1 h had elapsed. In the control trial, subjects inspired room air, whereas in the other trial the inhaled gas mixture was a 4% CO2:20% O2:76% N2 gas mixture. Oxygen uptake (VO2, liter.min-1), inspired minute ventilation (VI, liter.min-1), esophageal temperature (Tes, degree C), mean unweighted skin temperature (Tsk, degree C), mean heat flux (Q, W.m-2), and electromyographic (EMG, mV) activity of the trapezius muscle were recorded. VO2 and integrated EMG (IEMG) activity were used as the primary indicators of shivering thermogenesis. There was a tendency for elevated VO2, albeit not significant, in the CO2 trial compared to the air trial. We observed no significant differences in the IEMG between the air and CO2 trials. These results suggest that prolonged inhalation of a gas mixture containing 4% CO2 does not have a significant inhibitory effect on shivering thermogenesis and does not enhance the cooling rate of the body core. The absence of any shivering attenuation is most likely due to the small blood PCO2 increase incurred by inhalation of 4% CO2, compensation of hypercapnic-induced respiratory acidosis, and a strong thermal drive from core and peripheral regions. It is unlikely that elevated PICO2 levels contribute significantly to the etiology of hypothermia in divers.     

The effect of inhaled nitric oxide on pulmonary ventilation-perfusion matching following smoke inhalation injury

BACKGROUND: We previously reported that inhaled nitric oxide (NO) improved pulmonary function following smoke inhalation. This study evaluates the physiologic mechanism by which inhaled NO improves pulmonary function in an ovine model. METHODS: Forty-eight hours following wood smoke exposure to produce a moderate inhalation injury, 12 animals were anesthetized and mechanically ventilated (FIO2, 0.40; tidal volume, 15 mL/kg; PEEP, 5 cm H2O) for 3 hours. For the first and third hours, each animal was ventilated without NO: for the second hour, all animals were ventilated with 40 ppm NO. Cardiopulmonary variables and blood gases were measured every 30 minutes. The multiple inert gas elimination technique (MIGET) was performed during the latter 30 minutes of each hour. The data were analyzed by ANOVA. RESULTS: Pulmonary arterial hypertension and hypoxemia following smoke inhalation were significantly attenuated by inhaled NO compared with the values without NO (p < 0.05, ANOVA). Smoke inhalation resulted in a significant increase in blood flow distribution to low VA/Q areas (VA/Q < 0.10) with increased VA/Q dispersion. These changes were only partially attenuated by the use of inhaled NO. The SF6 (sulfur hexafluoride) retention ratio was also decreased by inhaled NO. Peak inspiratory pressures and pulmonary resistance values were not affected by inhaled NO. CONCLUSIONS: Inhaled NO moderately improved VA/Q mismatching following smoke inhalation by causing selective pulmonary vasodilation of ventilated areas in the absence of bronchodilation. This modest effect appears to be limited by the severe inflammatory changes that occur as a consequence of smoke exposure.     

The effect of low-dose inhalation of nitric oxide in patients with pulmonary fibrosis

The aim of this study was to determine whether low-dose inhalation of nitric oxide (NO) improves pulmonary haemodynamics and gas exchange in patients with stable idiopathic pulmonary fibrosis (IPF). The investigation included 10 IPF patients breathing spontaneously. Haemodynamic and blood gas parameters were measured under the following conditions: 1) breathing room air; 2) during inhalation of 2 parts per million (ppm) NO with room air; 3) whilst breathing O2 alone (1 L.min-1); and 4) during combined inhalation of 2 ppm NO and O2 (1 L.min-1). During inhalation of 2 ppm NO with room air the mean pulmonary arterial pressure (Ppa 25 +/- 3 vs 30 +/- 4 mmHg) and the pulmonary vascular resistance (PVR 529 +/- 80 vs 699 +/- 110 dyn.s.cm-5) were significantly (p < 0.01) lower than levels measured whilst breathing room air alone. However the arterial oxygen tension (Pa,O2) did not improve. The combined inhalation of NO and O2 produced not only a significant (p < 0.01) decrease of Ppa (23 +/- 2 vs 28 +/- 3 mmHg) but also, a remarkable improvement (p < 0.05) in Pa,O2 (14.2 +/- 1.2 vs 11.7 +/- 1.0 kPa) (107 +/- 9 vs 88 +/- 7 mmHg)) as compared with the values observed during the inhalation of O2 alone. These findings suggest that the combined use of nitric oxide and oxygen might constitute an alternative therapeutic approach for treating idiopathic pulmonary fibrosis patients with pulmonary hypertension. However, further studies must first be carried out to demonstrate the beneficial effect of oxygen therapy on pulmonary haemodynamics and prognosis in patients with idiopathic pulmonary fibrosis and to rule out the potential toxicity of inhaled nitric oxide, particularly when used in combination with oxygen.