Pulmonary Disease Division, Department of Medicine,
State University of New York/Downstate Health Sciences Center; and
Department of Veterans Affairs Medical Center, Brooklyn, New York
11209
We ...investigated the effect of altered
extracellular pH, mitochondrial function, and ATP content on
development of apoptosis in human pulmonary artery endothelial
cells after treatment with staurosporine (STS). STS produced a
concentration- and time-dependent increase in caspase-3 activity in pH
7.4 medium that reached a peak at 6 h. The increase in caspase
activity was associated with significant DNA fragmentation. Fluorescent
imaging of treated monolayers in pH 7.4 medium with
Hoechst-33342-propidium iodide demonstrated a large percentage of
apoptotic cells (~40%) with no evidence of necrosis. Caspase
activity, DNA fragmentation, and percentage of apoptotic cells were
reduced after STS treatment in acidic media (pH 7.0 and 6.6). The
Ca 2+ chelator
1,2-bis(2-aminophenoxy)ethane- N,N,N',N' -tetraacetic acid-AM
inhibited STS-induced apoptosis, whereas the rise in intracellular Ca 2+ concentration in STS-treated cells in pH 7.4 medium
was reduced in pH 7.0 medium. These results suggest that one mechanism
for inhibitory effects of acidosis may be a pH-induced alteration in
Ca 2+ signaling. Treatment with STS in the presence of
oligomycin (10 µM), an inhibitor of the mitochondrial
F 0 F 1 -ATPase, in glucose-free media abolished
caspase activation and DNA fragmentation in association with severe ATP
depletion (~2% of control cells). Imaging demonstrated a change in
the mode of cell death from apoptosis to necrosis under these
conditions. This change was linked to the level of ATP depletion,
because STS treatment in the absence of glucose or the presence of
oligomycin in media with glucose still leads to apoptosis in
the presence of only moderate ATP depletion. These results demonstrate
that pH, mitochondrial function, and ATP supply are important variables
that regulate STS-induced apoptosis in human pulmonary artery
endothelial cells.
caspases; extracellular pH; mitochondria
A growing body of evidence suggests that a variety of upper respiratory symptoms (URS) are associated with gastro-oesophageal reflux (GORD). The aim of this study was to determine the prevalence of ...endoscopic erosive, and non-erosive, oesophagitis among patients complaining of persistent URS, in the absence of typical GORD symptoms, and to compare them with a comparison group of similar age. A group of 110 patients aged 18-75, presenting with persistent URS with no suspicion of GORD symptoms, underwent upper flexible endoscopy, with biopsy sampling for histology, and was compared with a group of 117 patients of similar age undergoing endoscopy for reasons other than GORD. Patients affected with upper airway disorders, such as posterior laryngitis, chronic sinusitis and vocal fold nodules, had a significantly higher prevalence of oesophagitis of varying degrees (31 per cent) compared to the comparison population (15.4 per cent) (p < 0.01). These data suggest that in many patients with chronic URS occult gastro-oesophageal diseases are present.
Rabeprazole has been demonstrated to be a potent antisecretory agent and has been shown to be clinically effective in the treatment of acid-related diseases.
It was to determine the efficacy of ...rabeprazole at 20 and 40 mg in addition to amoxicillin and clarithromycin in the treatment of active Helicobacter pylori-positive duodenal ulcers compared with omeprazole 40 mg.
One hundred and twenty-seven patients were randomised into three treatment groups: 40 patients were treated with rabeprazole 40 mg daily, 42 patients with rabeprazole 20 mg daily and 45 patients with omeprazole 40 mg daily for 10 days. All patients received amoxicillin 1 g twice a day and clarithromycin 500 mg twice a day for 5 days. All patients were re-assessed at least 4 weeks after the end of the treatment.
According to the intention-to-treat (ITT) protocol, ulcer healing was observed in 90% of patients in the rabeprazole 40 group, in 85.7% in the rabeprazole 20 group and in 93.3% in the omeprazole 40 group. We observed H. pylori eradication in 90% ITT in the rabeprazole 40 group, in 80.9% ITT in the rabeprazole 20 group and in 88.8% ITT in the omeprazole 40 group. Statistical analysis did not show significant differences among the three groups.
A 10-day rabeprazole 20 mg regimen represents an efficacious and safe regimen for H. pylori eradication and ulcer healing.
We investigated the effect of altered extracellular pH, mitochondrial function, and ATP content on development of apoptosis in human pulmonary artery endothelial cells after treatment with ...staurosporine (STS). STS produced a concentration- and time-dependent increase in caspase-3 activity in pH 7.4 medium that reached a peak at 6 h. The increase in caspase activity was associated with significant DNA fragmentation. Fluorescent imaging of treated monolayers in pH 7.4 medium with Hoechst-33342-propidium iodide demonstrated a large percentage of apoptotic cells (~40%) with no evidence of necrosis. Caspase activity, DNA fragmentation, and percentage of apoptotic cells were reduced after STS treatment in acidic media (pH 7.0 and 6.6). The Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM inhibited STS-induced apoptosis, whereas the rise in intracellular Ca2+ concentration in STS-treated cells in pH 7.4 medium was reduced in pH 7.0 medium. These results suggest that one mechanism for inhibitory effects of acidosis may be a pH-induced alteration in Ca2+ signaling. Treatment with STS in the presence of oligomycin (10 microM), an inhibitor of the mitochondrial F0F1-ATPase, in glucose-free media abolished caspase activation and DNA fragmentation in association with severe ATP depletion (~2% of control cells). Imaging demonstrated a change in the mode of cell death from apoptosis to necrosis under these conditions. This change was linked to the level of ATP depletion, because STS treatment in the absence of glucose or the presence of oligomycin in media with glucose still leads to apoptosis in the presence of only moderate ATP depletion. These results demonstrate that pH, mitochondrial function, and ATP supply are important variables that regulate STS-induced apoptosis in human pulmonary artery endothelial cells.
In the present study we have assayed antioxidant enzymatic systems in erythrocytes from subjects with chronic cerebrovascular disease to correlate their involvement in red cell deformability. A ...significant decrease of glutathione peroxidase, reductase, catalase and superoxide dismutase activities has been found in human red blood cells from patients with chronic cerebrovascular disease when compared to the control group. The decrease in antioxidant enzymatic systems found in these patients was accompanied by reduced cellular resistance to hydrogen peroxide. An altered balance between the partially reduced forms of oxygen metabolism and the antioxidant enzymatic systems could play a crucial role in the haemorheological alteration frequently occurring in subjects affected by chronic cerebrovascular disease.
Background: Lung transplantation involves vagal nerve interruption resulting in sensory airway denervation and impairment of the cough
reflex. Following lung transplantation, it is unclear whether ...functional recovery of the cough reflex occurs over time. Our
objective was to evaluate the afferent limb of the cough reflex in lung transplant recipients.
Methods: The assessment of cough reflex involved upper airway anesthesia, conscious sedation, and fiberoptic bronchoscopy; the biopsy
forceps and a 5% dextrose solution were applied through the bronchoscope to the airway mucosa at the main carina, proximal
and distal to the anastomosis. A cross-sectional group of seven subjects underwent a single assessment, while eight subjects
in a longitudinal group underwent assessment at 1.5 and 12 months. Cough frequency was determined by counting the number of
audible coughs and abdominal muscle contractions measured with a surface electromyogram recorder. The airway anastomosis from
deceased subjects in the longitudinal group was examined for nerves.
Results: All seven subjects from the cross-sectional group demonstrated a similar cough frequency after mechanical and chemical irritation
of all airway sites. All subjects in the longitudinal group who were evaluated at 1.5 weeks had a cough response at all sites
except distal to the anastomosis. Twelve months after transplantation, cough was present at all sites. Immunohistochemical
staining for protein gene product 9.5, low-affinity neurotrophin, and vanilloid receptors demonstrated nerves in subepithelial
regions proximal and distal to the airway anastomosis.
Conclusion: In human lung transplant recipients, recovery of the cough reflex was noted 12 months after lung transplantation.
cough
denervation
innervation
lung transplantation
neurobiology
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