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Biomedical subjects

C T Yu

Publications and source records attributed to C T Yu.

At least 19 recordsLinked to original sources

Predicting the relative efficacy of verbal, pictorial, and tangible stimuli for assessing preferences of leisure activities.

We measured the relationships between choice stimulus modalities and three basic discriminations (visual, visual matching-to-sample, and auditory-visual) using the Assessment of Basic Learning Abilities test. Participants were 9 adults who had moderate to profound developmental disabilities. Their most and least preferred leisure activities, identified by prior preference assessments, were presented using choice stimuli in three modalities (tangibles, pictures, and verbal descriptions) in an alternating-treatments design. For 8 of the 9 participants, discrimination skills predicted the selections of choice stimuli associated with their preferred activities. The results suggest that choice stimulus modalities in preference assessment of leisure activities need to be matched to the discrimination skills of persons with developmental disabilities.

Adult↗

Visual-visual nonidentity matching assessment: a worthwhile addition to the assessment of basic learning abilities test.

The Assessment of Basic Learning Abilities test (ABLA) is a useful tool for choosing appropriate training tasks for persons with developmental disabilities. This test assesses the ease or difficulty with which persons are able to learn six hierarchically positioned discrimination tasks. A visual-visual nonidentity matching prototype task was examined to assess its (a). relation to the ABLA hierarchy, (b). predictive validity, and (c). test-retest reliability. Results from 23 participants with developmental disabilities suggest that visual-visual nonidentity matching is a worthwhile addition to the ABLA test and is positioned in the ABLA hierarchy above Level 4 (visual-visual identity matching) and below Level 6 (auditory-visual discrimination). The prototype visual-visual nonidentity matching task also demonstrated high predictive validity and test-retest reliability.

Adult↗

Endogenous nitric oxide inhibits neutrophil adherence to lung epithelial cells to modulate interleukin-8 release.

To investigate the effect of neutrophil adherence to epithelial cells on the release of interleukin 8 (IL-8), we measured neutrophil adherence in the presence or absence of IFN-gamma+TNF-alpha+IL-1beta (cytomix) stimulation on cultured A549 epithelial cells. The extent of neutrophil adherence to A549 epithelial cells was measured and the concomitant production of IL-8 and nitrite were assayed. The roles of adhesion molecules and nitrite in modulation of neutrophil adherence were examined by pretreatment with oversaturating ICAM-1 blocking antibody and L-NAME (1 mM), respectively. There was a time-dependent spontaneous and cytomix-induced release of IL-8 from epithelial cells, as well as a time-dependent increase in the magnitude of neutrophil adherence to epithelial cells. Stimulation of epithelial cells with cytomix induced a further increase in neutrophil adherence. Pretreatment with oversaturated ICAM-1 monoclonal antibody inhibited neutrophil adherence with or without cytomix stimulation. The inhibition of neutrophil adherence to epithelial cells with ICAM-1 monoclonal antibody or a semipermeable membrane downregulated the release of IL-8 with or without cytomix stimulation. Stimulation with cytomix decreased nitrite production. Both neutrophil adherence and L-NAME pretreatment significantly inhibited the production of nitrite. The inhibition of neutrophil adherence to epithelial cells with ICAM-1 monoclonal antibody or a semipermeable membrane upregulated nitrite production. Pretreatment with L-NAME failed to modify the spontaneous release of IL-8, but significantly enhanced the response to adherence and cytomix. In conclusion, endogenous nitric oxide may play a role in preventing neutrophil adherence to lung epithelial cells, thus modulating concomitant IL-8 release.

Antibodies, Monoclonal↗

Multiple signals required for cyclic AMP-responsive element binding protein (CREB) binding protein interaction induced by CD3/CD28 costimulation.

The optimal activation of cAMP-responsive element binding protein (CREB), similar to the full activation of T lymphocytes, requires the stimulation of both CD3 and CD28. Using a reporter system to detect interaction of CREB and CREB-binding protein (CBP), in this study we found that CREB binds to CBP only by engagement of both CD3 and CD28. CD3/CD28-promoted CREB-CBP interaction was dependent on p38 mitogen-activated protein kinase (MAPK) and calcium/calmodulin-dependent protein kinase (CaMK) IV in addition to the previously identified extracellular signal-regulated kinase pathway. Extracellular signal-regulated kinase, CaMKIV, and p38 MAPK were also the kinases involved in CREB Ser(133) phosphorylation induced by CD3/CD28. A reconstitution experiment illustrated that optimum CREB-CBP interaction and CREB trans-activation were attained when these three kinase pathways were simultaneously activated in T cells. Our results demonstrate that coordinated activation of different kinases leads to full activation of CREB. Notably, CD28 ligation activated p38 MAPK and CaMKIV, the kinases stimulated by CD3 engagement, suggesting that CD28 acts by increasing the activation extent of p38 MAPK and CaMKIV. These results support the model of a minimum activation threshold for CREB-CBP interaction that can be reached only when both CD3 and CD28 are stimulated.

Animals↗

Upregulation of inducible nitric oxide synthase and cytokine secretion in peripheral blood monocytes from pulmonary tuberculosis patients.

SETTING: Peripheral blood monocytes (PBM) are the main source of alveolar macrophages, which have an upregulation of inducible nitric oxide synthase (iNOS) in pulmonary tuberculosis (TB). TNF-alpha and IL-1 beta are thought to be involved in the immune response to mycobacterial infection. OBJECTIVE: To identify whether iNOS expression and cytokine release of PBM are upregulated and have a connection in TB infection. DESIGN: The expression of iNOS immunoreactivity on PBM from TB patients and normal subjects was measured by loading with anti-macrophage iNOS polyclonal primary antibody analyzed by flow cytometry. Expression of iNOS mRNA in PBM was detected by RT-PCR. The spontaneous generation of nitrite and cytokines (IL-1 beta and TNF-alpha) by cultured monocytes was also determined. RESULTS: Compared to normal subjects, iNOS immuno-reactivity, the capacity for spontaneous nitrite generation and the level of TNF-alpha or IL-1 beta secretion of PBM were significantly higher in TB patients. The amount of nitrite, TNF-alpha and IL-1 beta released from PBM of TB patients was inhibited by NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NOS. The level of iNOS immunoreactivity on PBM was highly correlated with nitrite generation both in all the subjects studied and in TB patients alone. Spontaneous TNF-alpha production showed a stronger correlation with nitrite production than with IL-1 beta. CONCLUSION: The NO and cytokine synthase activities of monocytes appear to be concomitantly upregulated in response to mycobacterial infection. The enhanced NO generation by monocytes in TB patients may play an autoregulatory role in amplifying the synthesis of pro-inflammatory cytokines.

Female↗

Repair of cardiac defects through a shorter right lateral thoracotomy in children.

BACKGROUND: Median sternotomy is a conventional approach for correction of cardiac defects for many years; however, the cosmetic result is poor. Therefore, right lateral thoracotomy was tested as an alternative procedure with a better cosmetic outcome. METHODS: Between October 1994 and February 1999, 683 patients underwent correction of congenital cardiac malformations during a cardiopulmonary bypass through right lateral thoracotomy involving a shorter incision through the third or the fourth intercostal space. All of the patients were children. The average age was 3.26+/-1.67 years (range, 4 months to 7 years). The average weight was 13.59+/-4.37 kg (5 to 40). The patients had various cardiac defects and associated anomalies. RESULTS: Only 2 patients died after operation, 1 from low cardiac output and the other from severe pulmonary infection. The hospital morbidity was lower. The mean cardiopulmonary bypass time was 58.67+/-35.11 minutes (range, 16 to 430 minutes), the mean aortic cross-clamping time was 35.03+/-24.84 minutes (range, 3 to 205 minutes). The postoperative average mechanical ventilation time was 19.23+/-39.11 hours (range, 2 to 391 hours), and the mean postoperative stay was 8.55+/-12.54 days (range, 5 to 293 days). CONCLUSIONS: The right lateral thoracotomy incision is a safe and effective alternative to a median sternotomy for correction of cardiac defects. Advantages of this approach compared with median sternotomy are less injury, maintenance of the continuity and the integrity of the bony thorax, and prevention of the development of "pigeon-chesting." The scar is less visible, hence, the cosmetic result can meet patient expectations. This procedure is consistent with the idea of minimal invasive surgery.

Cardiopulmonary Bypass↗

Erythromycin inhibits beta2-integrins (CD11b/CD18) expression, interleukin-8 release and intracellular oxidative metabolism in neutrophils.

Macrolides have therapeutic benefits on chronic inflammatory airway diseases. Thus, macrolides are supposed to have variable biological effects apart from antimicrobial activity. Neutrophil adherence and influx with oxidants and cytokines production implicates involvement in airway inflammation. To investigate whether erythromycin (EM) affects neutrophil activity in vitro, lipopolysaccharide (LPS)-treated neutrophils were continuously incubated for 4 h in the absence or presence of increasing doses of EM from 1 microg ml(-1) to 100 microg ml(-1) in the last 2 h. Leukocyte adhesion molecules Mac-1 and intracellular H2O2(DCFH) were determined by flowcytometric assay. IL-8 and TNFalpha in supernatant was measured by ELISA method. The expression of Mac-1 and mean intracellular DCF fluorescence intensity (DCFH) of neutrophils significantly increased after stimulation with LPS. Pretreatment with EM significantly decreased LPS induced Mac-1 expression on neutrophils compared with LPS stimulation only. EM alone (100 microg ml(-1)) also decreased Mac-1 expression on neutrophils. EM significantly reduced the LPS-increased DCFH. EM alone (100 microg ml(-1)) also caused a decrease in DCFH. Increasing doses of EM also significantly decreased the IL-8 released by LPS-stimulated neutrophils. In conclusion, EM exerts a direct effect on the neutrophils by downregulating the expression of beta2-integrin on neutrophils, thus leading to a decrease in the intracellular H2O2, as well as the production of IL-8. Our conclusion provides an explanation for the clinical efficacy of erythromycin in neutrophil-mediated airway inflammation.

Anti-Bacterial Agents↗

Nitric oxide modulates interleukin-1beta and tumor necrosis factor-alpha synthesis by alveolar macrophages in pulmonary tuberculosis.

Interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha released from alveolar macrophages (AM) in pulmonary tuberculosis (TB) are important in host defense against mycobacterial infection. Nitric oxide (NO) production is enhanced in AM of TB patients. We examined whether NO was implicated in (IL)-1beta and TNF-alpha synthesis by AM of TB patients. Purified AM were retrieved by bronchoalveolar lavage from 11 TB patients and 10 normal subjects, and were cultured with or without the NO inhibitor N(G)-monomethyl-L-arginine (L-NMMA). The release of IL-1beta and TNF-alpha, and expression of their messenger RNAs (mRNAs), were determined by enzyme-linked immunosorbent assay and Northern blot analysis. The release of IL-1beta and TNF-alpha was greater from AM of TB patients than from AM of normal subjects. L-NMMA inhibited nitrite, IL-1beta, and TNF-alpha production in TB patients. The mRNA expression for IL-1beta and TNF-alpha was upregulated in TB patients and was depressed by L-NMMA. Immunocytochemistry done with a monoclonal antibody against the p65 subunit of nuclear factor (NF)-kappaB showed that NF-kappaB was highly expressed and translocated to the nuclei of AM from TB patients, and was inhibited by L-NMMA. Inhibition of NF-kappaB by pyrrolidine dithiocarbamate attenuated IL-1beta and TNF-alpha synthesis. In conclusion, enhanced NO generation by AM of TB patients plays an autoregulatory role in amplifying the synthesis of proinflammatory cytokines, probably through NF-kappaB activation.

Adult↗

Endotoxemia augments neurogenic plasma exudation in guinea pig lungs.

BACKGROUND: Lipopolysaccharide (LPS) is closely associated with the development of infection-induced deleterious pulmonary reactions. In this study, we investigated the enhancement effects of LPS on tachykinin-mediated plasma exudation in the lungs of guinea pigs. The role of oxidants was also explored. METHODS: Intravenous LPS (100 mu kg-1) or its vehicle was administered 0 to 3 hours prior to bilateral electrical or sham stimulation of the cervical vagus nerves in animals anesthetized with urethane and artificially ventilated. Plasma exudation into the lungs was assessed by measurement of extravasated 125I-albumin which had been intravenously administered before stimulation. RESULTS: The plasma exudation in the lungs increased after bilateral cervical vagal stimulation. LPS alone did not induce significant plasma exudation. The vagally-mediated plasma exudation was enhanced by LPS with the peak effect 1 hour after LPS administration. LPS also enhanced exogenous substance P (10(-8) mol kg-1, i.v.)-induced plasma exudation. The vagally-induced plasma exudation was abolished by a specific neurokinin-1 (NK-1) receptor antagonist, L-732,138. The LPS-induced enhancement response was also attenuated by L-732,138. The vagally-induced plasma exudation was not affected by superoxide dismutase (SOD, 5000 U kg-1, i.p.) pretreatment. However, SOD significantly inhibited the LPS-enhanced neurogenic plasma leakage. The LPS-induced enhancement was not completely abolished by either L-732,138 or SOD pretreatment alone, but by a combination of both. CONCLUSION: LPS augments neurogenic plasma exudation partly through NK-1 receptors to increase vascular permeability and partly via the generation of oxidative metabolites. Tachykinins released from nerve endings may contribute to endotoxin-related pulmonary inflammatory responses.

Animals↗

The value of transbronchial lung biopsy in the diagnosis of peripheral lung tumors according to cell type.

BACKGROUND: Transbronchial lung biopsy (TBLB) is a useful diagnostic tool for peripheral lung tumors. However, the success rate is variable. Our study was designed to investigate the value of TBLB without fluoroscopic guidance in the diagnosis of variable cell types of peripheral lung cancers. METHODS: A retrospective study was conducted to investigate a total of 597 patients who had undergone fiberoptic bronchoscopy for lung mass on chest X-ray in Chang Gung Memorial Hospital from January 1996 to December 1998. The lung masses were proven to be malignant by cytology and histology. RESULTS: Of 358 patients (60.0%) proven with malignancy, 107 patients presented with peripheral lung cancer (17.9%), including 59 with adenocarcinoma, 26 with squamous cell carcinoma, 11 with poorly differentiated carcinoma, 3 with small cell carcinoma, and 8 with metastatic cancers. The diagnostic rate of peripheral lung cancer by TBLB reached 54.2%. The sensitivity rates of detection of non-small cell type by TBLB were adenocarcinoma, 50.9%; squamous cell carcinoma, 61.5%; and poorly differentiated carcinoma, 72.7%, while that of small cell carcinoma was 100%. In contrast, the sensitivity rate of TBLB for metastatic cancers was lower (12.5%) than for primary lung cancers. Repeated TBLB of peripheral lung cancers increased the diagnostic rate from 49.5% to 54.2%. CONCLUSION: TBLB is an effective bronchoscopic sampling technique in the diagnosis of peripheral lung tumors without additional risk. The use of TBLB in the clinical routine should be encouraged.

Biopsy, Needle↗

Value of bronchoalveolar lavage combined with transbronchial lung biopsy in the diagnosis of peripheral lung cancer.

BACKGROUND: Bronchoalveolar lavage (BAL) is a safe and established procedure to evaluate interstitial lung diseases and pulmonary tuberculosis. The diagnostic rate of peripheral lung cancer invisible through bronchoscopy applied by transbronchial lung biopsy (TBLB) is still low. The study was designed to evaluate whether BAL combined with TBLB might improve the positive value in the diagnosis of peripheral lung cancer. METHODS: Thirty-seven of 72 patients who presented with peripheral lung lesions in chest radiography were proven to have a malignancy according to the final reports of cytology, histology, and clinical evidence. Each patient received BAL with or without TBLB. The patterns of chest radiography of the malignancies included 33 of infiltrative type and 4 of massive or nodular type. RESULTS: BAL alone revealed positive malignant cells in 18 of 37 cases (sensitivity 48.6%), and the diagnostic value significantly increased to 73.0% (p < 0.05) with BAL + TBLB. In the infiltrative type of lung cancer, the diagnostic rate of BAL + TBLB (78.8%) was significantly improved compared to that of BAL alone (51.5%, p < 0.05). There was no difference of diagnostic value in those with nodular type. BAL + TBLB can achieve a very high diagnostic rate (100%) in cases of metastatic malignancy (n = 4). Only 2 patients developed bleeding post BAL + TBLB, and it was easily controlled by epinephrine spraying. One patient developed self-limited hemoptysis. CONCLUSION: BAL + TBLB is a safe and valuable procedure to achieve a high sensitivity rate in the diagnosis of peripheral lung cancer, especially of the infiltrative type.

Adult↗

[Effect of solution pH value on the chelation structure of zinc acexamate by electrospray ionization mass spectrometry].

AIM: To study the effect of solution pH value on the chelation structure of zinc acexamate. METHODS: A series of samples at different solution pH values were prepared by 10% HCl or 1 mol.L-1 NH3.H2O. Then API/TOFMS with electrospray ion source was applied to assay the samples. The nitrogen curtain gas and nebulizer gas were adjusted to a constant flow rate of 0.6 microL.min-1 and 2 microL.min-1 respectively. Samples were infused into the electrospray interface using a 500 microL syringe pump at a flow rate of 5 microL.min-1. Mass spectra were acquired in positive ion modes by scanning over the range of m/z 100-1,000. RESULTS: The chelation structure of zinc acexamate is stable at pH 2.54 and it can be easy to form the ion (M + ZnY)+ (Y = CH3CONH(CH2)5COO-) and (2M + Na)+ in this condition. CONCLUSION: The drug is an effective antiulcer agent. It may decrease the acidity of stomach juice, and form a polymer to protect the ulcer.

Aminocaproates↗

Hypodense alveolar macrophages in patients with diabetes mellitus and active pulmonary tuberculosis.

SETTING: Alveolar macrophages (AM), a heterogeneous cell population, play a critical role in eliminating mycobacterial infections in collaboration with lymphocytes. Patients with diabetes mellitus (DM) show increased susceptibility to pulmonary tuberculosis (TB) infection. It is still uncertain whether there is a defect in T cell or AM activation in patients with DM against TB infection. OBJECTIVE: To study the difference in activation status of AM and T cells between patients with TB + DM and TB alone. METHOD: The heterogeneity of AM from 14 patients with TB + DM, 9 with TB alone, 10 normal subjects and 8 DM alone patients, was studied using Percoll density fractionation. The intracellular H2O2 production of AM before and after stimulation with phorbol myristate acetate (PMA) or F-Met-Leu-Phen (FMLP) was assayed by loading cells with 2',7'-dichlorofluorescin (DCFH) and analyzed by flow cytometry. Lymphocytes subsets (CD3, CD4, CD8) and their activation status (CD25) in bronchoalveolar lavage were also measured. RESULTS: The proportion of the least dense AM (< 1,030 g/ml) and the magnitude of DCFH oxidation of AM was higher in TB patients than in normal subjects, regardless of DM. Patients with TB + DM had a significantly lower proportion of the least density AM fraction than TB alone patients, regardless of disease extent. Among TB patients, the proportion of the least dense AM was inversely correlated with the bacterial load on sputum and the disease extent on chest radiograph. Stimulation of AM with PMA or FMLP induced an increase in the hypodense AM subpopulations and enhanced intracellular H2O2 generation in patients with TB + DM and to a similar extent in normal subjects, but not in patients with TB alone. There was no significant difference in CD3 numbers, CD4/CD8 ratio, and CD25+ cells between patients with TB alone and TB + DM. The activation status of AM or T lymphocytes from DM alone patients was not significantly different from those from normal subjects. CONCLUSION: Hypodense subpopulations of AM increase in active TB patients and are related to the disease severity as well as activation status of AM. AM in TB patients complicated with DM was less activated, and may be contributory to the susceptibility to mycobacterial infection.

Adult↗

Increased level of exhaled nitric oxide and up-regulation of inducible nitric oxide synthase in patients with primary lung cancer.

Monocyte-macrophage series have an important role in host surveillance against cancer. The cytotoxic/cytostatic activity of macrophages is, to a great extent, attributed to the up-regulation of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO). Here, in 28 patients with primary lung cancer and 20 control subjects, we measured the concentration of exhaled NO and nitrite in epithelial lining fluid (ELF) using a chemiluminescence NO analyser, and studied NOS expression in alveolar macrophages (AM) and lung tissues by flow cytometry; immunohistochemical analysis was also undertaken. The mean fluorescence intensity (FI) of iNOS expression in AM was significantly increased in patients with lung cancer (tumour side 263.5 +/- 15.2 FI, normal side 232.4 +/- 18.6 FI; n = 28) compared with that in control subjects (27.3 +/- 3.2 FI; n = 20, P< 0.001). The level of exhaled NO from cancer patients (16.9 +/- 0.9 p.p.b.; n = 28) was significantly higher than that in the control group (6.0 +/- 0.5 p.p.b.; n = 20, P < 0.001). The level of nitrite was also significantly higher in ELF from cancer patients (tumour side 271.1 +/- 28.9 nM and normal side 257.4 +/- 19.6 nM vs control subjects 32.9 +/- 4.1 nM; P< 0.001). The intensity of iNOS expression in AM was correlated with the level of exhaled NO (rs = 0.73, n = 76, P< 0.001) and the nitrite released in ELF (rs = 0.56, n = 76, P< 0.001). The nitrite generation of cultured AM from patients with lung cancer was significantly enhanced compared with that of control subjects after culture for 24 h (tumour side 5.75 +/- 0.69 and normal side 5.68 +/- 0.58 microM per 106 cells vs control group 38.3 +/- 3.6 nM per 106 cells; P< 0.001). The distribution of iNOS was identified in AM, tumour-associated macrophages, endothelium, chondrocytes, airway epithelium of both lungs and malignant cells (adenocarcinoma and alveolar cell carcinoma) of cancer patients. cNOS was labelled in alveolar macrophages, endothelial cells and nerve elements from lung tissue. Our results indicate that, in patients with primary lung cancer, the production of NO from alveolar macrophages was increased as a result of the up-regulation of iNOS activity. The increased NO production was not specific to the tumour side and might be attributed to the tumour-associated non-specific immunological and inflammatory processes of the host.

Adult↗

Increased exhaled nitric oxide in active pulmonary tuberculosis due to inducible NO synthase upregulation in alveolar macrophages.

Nitric oxide (NO) plays an important role in resistance to Mycobacterium tuberculosis infection. Our aim was to determine whether inducible NO synthase (iNOS) expression and generation of reactive nitrogen intermediates (RNI) by alveolar macrophages (AM) are increased in patients infected with M. tuberculosis. NO levels in the exhaled air of 19 active pulmonary tuberculosis (TB) and 14 control subjects were measured using a chemiluminescence NO analyser. The expression of iNOS on AM was studied by labelling AM with anti-mac iNOS polyclonal antibody analysed with a flow cytometer. The spontaneous generation of RNI by cultured AM was also measured. Data are presented as mean+/-SEM. The level of NO in exhaled air was higher in patients with active TB (16.2+/-1.2 parts per billion (ppb)) compared to control subjects (6.5+/-0.9 ppb), p<0.0001. Exhaled NO decreased with anti-TB treatment. Compared to control subjects (29.0+/-4.5 fluorescence intensity (FI)), iNOS expression on AM was upregulated in TB patients (86.3+/-12.5 FI) p<0.001 and the capacity for spontaneous generation of nitrite was enhanced. Nitrite production was inhibited by N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of iNOS. The expression of iNOS on AM was related to the concentration of exhaled NO (r=0.66, p<0.001) and the nitrite generation capacity of AM (r(s)=0.77, p<0.001). We conclude that the increase in exhaled nitric oxide observed in patients with active pulmonary tuberculosis is due to an upregulation of inhaled NO synthase expression in alveolar macrophages which have an enhanced capacity for nitric oxide production.

Cells, Cultured↗

Cloning, sequencing, and expression of the rpoD gene encoding the primary sigma factor of Xanthomonas campestris.

A DNA fragment encoding the primary sigma factor from Xanthomonas campestris pv. campestris was cloned and sequenced. The gene (rpoD) encodes a polypeptide of 622 amino acids with a calculated MW of 70,700. The deduced amino acid sequence exhibits extensive sequence homology to the conserved regions of the primary sigma factors from bacteria. The gene product expressed in Escherichia coli, detected by Western blot analysis, had a MW similar to that estimated for the purified protein in SDS-PAGE. The NH2-terminal amino acid sequence determined chemically matched with that deduced from the nucleotide sequence of the rpoD gene. The calculated pI value (9.31) for the X. campestris primary sigma factor is much higher than the values observed for the analogous proteins from other bacteria.

Amino Acid Sequence↗

Inhaled gentamicin reduces airway neutrophil activity and mucus secretion in bronchiectasis.

To investigate whether aerosolized gentamicin (GM) prevents myeloperoxidase (MPO)-mediated airway injury and mucus hypersecretion, a short course of aerosol therapy (3 d) with GM 40 mg or 0.45% saline (saline) twice per day was conducted. Twenty-eight patients with bronchiectasis and mucus hypersecretion after adequate chest care and hydration were enrolled in a randomized, double-blind fashion. MPO levels in sputum collected on arising were determined by fluorometric assay at 655 nm before and after treatment. The sputum MPO level significantly decreased in patients receiving aerosolized GM, from 0.22 +/- 0.04 to 0.14 +/- 0.04 U/g (n = 15), but not in patients with saline inhalation (0.23 +/- 0.03 to 0.17 +/- 0.02 U/g; n = 11). The daily sputum amount significantly decreased from 94.6 +/- 21.6 to 58.1 +/- 17.8 ml (n = 13, p < 0.01) in the GM group, whereas it increased from 78.6 +/- 25.4 ml to 120.5 +/- 33.9 ml (n = 11, p < 0.05) in the saline group. The change in the amount of daily sputum was related to that in the sputum MPO level in the GM group (r = 0.61; p < 0.01). Inhalation of GM, but not saline, significantly (p < 0.05) increased the value of peak expiratory flow (PEF) from 186.4 +/- 25.1 to 216.4 +/- 26.4 L/min and decreased the variability of PEF from 24.6 +/- 5.1 to 6.1 +/- 2.3 %. The nocturnal desaturation and the 6-min walking distances were also significantly improved in the GM group (11.2 +/- 3.8 to 0.6 +/- 0.5 min/h; 324.9 +/- 43.1 to 408.1 +/- 25.9 m; p < 0.05; respectively), but not in the saline group. Subjective improvements in the Borg scale and self-sputum assessment were found in the GM group only. In conclusion, aerosolized GM is effective in improving airway hypersecretion and inflammation in patients with bronchiectasis.

Administration, Inhalation↗