Role of histamine in altering fluid recycling in normal and post-traumatic rabbit peritoneum.

This study aims to investigate if histamine induces electrochemical alterations in the normal and post-traumatic peritoneum. Peritoneal rabbit specimens were obtained before surgery and 10 days post-operatively and were mounted in Ussing chambers. Histamine solutions were added facing the intra-peritoneal and outer-peritoneal surface. Dimetindene maleate-, cetirizine-, and ranitidine-pretreated specimens were used to investigate histamine receptor involvement, whereas amiloride- and ouabain-pretreated specimens were used to investigate ion transportation blockage involvement. Trans-mesothelial resistance (R(TM)) was determined. Histamine-increased R(TM) intra-peritoneally and decreased it outer-peritoneally. A less intense effect was induced in post-traumatic specimens. Dimetindene maleate, cetirizine, amiloride, and ouabain totally inhibited this effect, whereas ranitidine only had a partial effect. Histamine induces electrochemical alterations in the normal and post-operative peritoneum. This effect is mediated by interaction with histamine receptors, hindering the normal process of ion trans-mesothelial transportation.

IGF-1 alters the human parietal pleural electrochemical profile by inhibiting ion trans-cellular transportation after interaction with its receptor.

OBJECTIVE: The effect of IGF-1 in the human pleural permeability and the underlying mechanisms involved were investigated. DESIGN: Specimens from thoracic surgical patients were mounted in Ussing chambers. Solutions containing IGF-1 (1 nM-100 nM) and IGF-1 Receptor Inhibitor (1 µΜ), amiloride 10 µM (Na(+) channel blocker) and ouabain 1 mM (Na(+)-K(+) pump inhibitor) were used in order to investigate receptor and ion transporter involvement respectively. Trans-mesothelial Resistance (R(TM)) across the pleural membrane was determined as a permeability indicator. Immunohistochemistry for IGF-1 receptors was performed. RESULTS: IGF-1 increased R(TM) when added on the interstitial surface for all concentrations (p=.008, 1 nM-100 nM) and decreased it on the mesothelial surface for higher concentrations (p=.046, 100 nM). Amiloride and ouabain inhibited this effect. The IGF-1 Receptor Inhibitor also totally inhibited this effect. Immonuhistochemistry demonstrated the presence of IGF-1 receptors in the pleura. CONCLUSIONS: It is concluded that IGF-1 changes the electrophysiology of the human parietal pleura by hindering the normal ion transportation and therefore the pleural fluid recycling process. This event is achieved after IGF-1 interaction with its receptor which is present in the human pleura.

Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer

OBJECTIVES: The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival. METHODS: We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxiainducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice. RESULTS: A significant difference (p=0.022) in hypoxia-inducible factor 1α expression was observed between nonsmall cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxiainducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher's exact test, p=0.001) when all types of lung cancer were examined, either collectively or separately. CONCLUSIONS: The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.

Nonsteroidal anti-inflammatory drugs alter the human mesothelial pleural permeability via ion cellular transportation by inhibiting prostaglandin synthesis.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in clinical practice as analgesics or anti-inflammatory drugs. Studies have implicated them in participating in permeability throughout various tissues such as the kidneys and lungs. OBJECTIVE: The effect of NSAIDs on the pleural permeability and the underlying mechanisms whereby this effect is mediated were investigated. METHODS: Parietal pleural specimens were obtained from patients subjected to thoracic surgery and were mounted in Ussing chambers. Solutions containing paracetamol, acetylsalicylic acid, diclofenac, lornoxicam, parecoxib and ibuprofen were added in the chambers facing the pleural and the outer-pleural surface. Prostaglandin E(2) was similarly used to investigate prostaglandin synthesis involvement at low and high doses. Amiloride- and ouabain-pretreated specimens were used in order to investigate ion transportation involvement. Transmesothelial resistance (R(TM)) was determined as a permeability indicator. RESULTS: Paracetamol, acetylsalicylic acid, diclofenac, lornoxicam and ibuprofen increased R(TM) on the pleural and outer-pleural surface, inhibited by amiloride and ouabain. Parecoxib had no effect on the R(TM). Prostaglandin decreased R(TM) on the pleural and outer-pleural surface inhibited by amiloride, ouabain and ibuprofen. CONCLUSION: NSAIDs, except parecoxib, induce a rapid decrease of the pleural permeability by inhibiting cellular transportation, an effect that is mediated by prostaglandin synthesis inhibition.

Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer.

OBJECTIVES: The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival. METHODS: We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxiainducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice. RESULTS: A significant difference (p=0.022) in hypoxia-inducible factor 1α expression was observed between nonsmall cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxiainducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher's exact test, p=0.001) when all types of lung cancer were examined, either collectively or separately. CONCLUSIONS: The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.

Pleural electrophysiology alterations in spontaneous pneumothorax patients.

Physiology changes of the pleura in spontaneous pneumothorax (SP) patients are not known with its etiology remaining unclear. The aim of the study was to investigate the pleural electrophysiology profile of SP patients and to compare it with the normal pleural electrophysiology. Specimens from nine patients who underwent surgery for persistent SP were obtained after wedge resection (apical visceral) and apical pleurectomy (apical parietal) alongside with parietal specimens over the 8th-9th rib (caudal parietal). Specimens were mounted in Ussing chambers and trans-mesothelial resistance (R(TM)) was determined as a permeability indicator. Amiloride (Na(+) channel inhibitor) was used as an ion channel transportation inhibitor. R(TM) of apical visceral, apical parietal and caudal parietal pleura of SP patients was increased (P=0.042, 0.025 and 0.001, respectively) when compared to disease-free specimens obtained from lung lesion patients. Amiloride was unable to increase R(TM) in all cases. Histopathology of apical and caudal parietal specimens revealed inflammatory infiltration. In conclusion, pleural electrophysiology is altered in SP patients when compared with the electrophysiology of disease-free specimens. A similar observation was made for caudal pleura suggesting diffuse process that possibly involves inflammation as shown by the histopathology.

Pleural electrophysiology variations according to location in pleural cavity.

The aim of the study was to compare the electrophysiology profile of sheep pleura originated from different locations of the pleural cavity with the respective profile in humans. Sheep specimens obtained from upper and lower lung lobes, 1st-4th and 8th-12th rib, ventral-dorsal diaphragm and mediastinum were mounted between Ussing chambers. Human visceral tissues were obtained from patients subjected to lobectomy. Trans-mesothelial resistance (R(TM)) was determined as an indicator of the tissue permeability, while amiloride and ouabain were used as inhibitors of cellular transportation via ion transporters. Control values R(TM) were low in lower lobe visceral, caudal costal parietal and diaphragmatic pleura. Amiloride increased R(TM) at all locations except upper visceral and mediastinum. Higher R(TM) increases were found in caudal parietal and dorsal diaphragmatic samples. Ouabain increased R(TM) of lower visceral, caudal parietal and diaphragmatic pleura but not of mediastinal specimens. Observations made in sheep tissue were comparable with human visceral, parietal and mediastinal regions. In conclusion, results suggest heterogeneity of trans-mesothelial permeability among different pleural locations in sheep as was the case for humans. Thoracic surgeons should consider physiology function of each part of pleural cavity before pleural tissue manipulation. Observations made in sheep may be used to understand human physiology.

Pulmonary function and circulating adhesion molecules in patients with diabetes mellitus.

BACKGROUND: Lung function in diabetes has been reported in several studies with contradictory results. Diabetes mellitus increases expression of adhesion molecules through hyperglycemia. These molecules play an important role in the pathophysiological dysfunction of the vasculature. OBJECTIVE: To explore the possible relationship between lung function and circulating levels of adhesion molecules in diabetes. METHODS: Sixteen type 1 diabetic patients, 33 type 2 diabetic patients and 22 healthy subjects matched for age and sex were studied. Spirometry measurements were performed and pulmonary diffusion capacity for carbon monoxide (DLco) was measured in sitting and supine positions by the single-breath method corrected by alveolar volume (VA). Glycosylated hemoglobin, retinopathy and nephropathy were included as parameters of metabolic control and diabetic complications. Circulating levels of soluble E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were determined in all subjects. RESULTS: Diabetic subjects showed lower variation in DLco and DLco/VA by changing posture from sitting to supine position (P=0.043 and P<0.001, respectively), and showed reduced total lung capacity (P<0.001) and forced expiratory volume in 1 s/forced vital capacity (P=0.009) compared with healthy control subjects. Serum concentrations of E-selectin were elevated in diabetic patients (P<0.001). There was no difference in serum VCAM-1 concentrations between diabetic and control subjects. On stepwise regression analysis, E-selectin concentrations were the most important contributing factor to the variation in DLco/VA. CONCLUSIONS: Diabetic patients show lower pulmonary volumes and variation in DLco by changing posture from sitting to supine position, and they also show increased levels of E-selectin. A possible explanation is impaired pulmonary microvasculature, because adhesion molecules seem to be sensitive markers of endothelial activation and damage seen in diabetes.

Diabetes mellitus vs. Raynaud disease: different lung vascular bed disorders.

BACKGROUND: In type II diabetes mellitus there are few data concerning pulmonary function abnormalities. In normal subjects and in patients with primary Raynaud phenomenon, cold pressor test induces a decrease in carbon monoxide single-breath diffusing capacity (DL,co) but not in secondary Raynaud phenomenon. Our objective was to assess evaluation of lung diffusion capacity postural changes in diabetes mellitus and in secondary Raynaud phenomenon, two diseases with different pulmonary capillaries functional disorders. METHODS: Twenty-five patients with type II diabetes mellitus (mean age 52.24 years), 17 patients with secondary Raynaud phenomenon (mean age 47.06 years), non-smokers without pulmonary or heart disease, and 26 healthy matched subjects (mean age 47.50 years) underwent lung diffusion capacity measurements by single-breath method also corrected by alveolar volume (DL,co) in sitting and supine positions. RESULTS: Patients with diabetes mellitus exhibited lower values of DL,co and DL,co/VA measurements in comparison with subjects with Raynaud phenomenon and control group (p <0.01). Additionally, they had a significant decrease in DL,co in supine compared to sitting position (83.88 +/- 16.53 vs. 89.68 +/- 18.03, p = 0.023). To the contrary, supine position in secondary Raynaud phenomenon and in control group after cold pressor test showed a significant increase in DL,co/VA (120.93 vs. 109.78 in Raynaud and 114.36 vs. 99.47 in control group, p <0.001). CONCLUSIONS: Postural changes of lung diffusion capacity could be used as a simple, non-invasive method to detect vascular disease resulting from different pathophysiologic mechanisms such as diabetes mellitus and Raynaud phenomenon.