Quinolines attenuate PAF-induced pulmonary pressor responses and edema formation.

In the present study we have investigated the mechanisms of pulmonary edema caused by platelet-activating factor (PAF) in isolated rat lungs as well as in mice in vivo. In blood-free perfused and ventilated rat lungs, PAF increased lung weight by 0.59 +/- 0.18 g. The cyclooxygenase inhibitor aspirin (500 microM) blocked this response by one-third, and the quinolines quinine (330 microM), quinidine (100 microM), and chloroquine (100 microM) by two-thirds. Lipoxygenase inhibition (10 microM AA861) alone or in combination with thromboxane receptor antagonism (10 microM SQ29548) had no effect on PAF-induced weight gain. In combination with aspirin, quinine or quinidine completely prevented PAF-induced weight gain and the concomitant increase of the capillary filtration coefficient (K(f,c)). Pretreatment with quinine in vivo prevented not only PAF-, but also endotoxin-induced edema formation as assessed by Evans Blue extravasation. In addition, in vivo quinine prevented the endotoxin-induced release of tumor neurosis factor (TNF). Furthermore, in perfused lungs quinine reduced the PAF-induced increases in airway and vascular resistance, as well as thromboxane release. These findings demonstrate the following anti-inflammatory properties of quinolines: reduction of thromboxane and TNF formation; reduction of PAF-induced vasoconstriction and bronchoconstriction; and attenuation of PAF- and lipopolysaccharide (LPS)-induced edema formation. We conclude that the PAF- induced edema consists of two separate mechanisms, one dependent on an unknown cyclooxygenase metabolite, the other one sensitive to quinolines.

Simultaneous detection of cell volume and intracellular pH in isolated rat duodenal cells by confocal microscopy and BCECF.

The combination of confocal laser scan microscopy and the pH-sensitive fluorescent dye BCECF allowed us to record simultaneously intracellular pH, cell viability and relative cell volume. pH was measured by using the pH-sensitive excitation wavelength at 488 nm and the pH-independent excitation wavelength at 442 nm to obtain ratio images. Cell volume was traced by measuring fluorescence dye concentration at 442 nm. Isolated villus tip rat duodenal enterocytes were exposed to 20 mM NH4Cl, sodium free, or 1 mM amiloride buffer. Sodium free buffer and amiloride buffer acidified the cells. Cell volume did not change in sodium free buffer, or NH4Cl exposure, but amiloride led to an increase in cell volume of 20%. After acidification of the duodenal cells, amiloride buffer increased cell volume by almost 50%. These studies revealed that cell volume regulation during pH changes in short-living cells could easily be detected by confocal microscopy and BCECF.

Intracellular pH-measurements in rat duodenal mucosa in vitro using confocal laserscan microscopy.

An improved technique was developed to measure intracellular pH-changes in in vitro duodenal mucosa. A confocal laserscan microscope was equipped with a second laser to permit dual wavelength excitation measurements employing BCECF (2'7'-bis-2-carboxyethyl-5-(and-6)carboxyfluorescein), a pH-sensitive fluorescent dye. Intact rat duodenal epithelium was mounted in a microperfusion chamber and loaded with BCECF via submucosal injection. Viability of the epithelial cells could be directly monitored by estimating the nucleus-to-cytoplasm ratio of the fluorescence intensity of BCECF. A calibration procedure using isolated duodenal cells, allowed estimation of the apparent intracellular pH. Initial apparent intracellular pH was 7.32 +/- 0.12, identical to that of isolated duodenocytes. Exposure of the duodenal epithelium to 60 mM NH4Cl led to a steady increase in apparent intracellular pH of 0.46 units within 2 min. Luminal application of 0.01 N HCl led to a steady decrease in apparent intracellular pH of 0.53 pH units within 1 min and was followed by a slow increase to baseline level after acid removal. Thus, confocal laserscan microscopy in combination with BCECF allowed noninvasive monitoring of intracellular pH-changes in single cells of an intact duodenal epithelium.

[Surgical relevance of diagnostic imaging of abdominal tumors--decision making in pancreatic tumor]. / Chirurgische Relevanz bildgebender Diagnostik bei abdominellen Tumoren--Entscheidungswege beim Pankreas.

Imaging of tumors of the pancreas may have a series of significant implications for surgical decision making. First of all verification and localization of a suspected tumor is crucial. Later on, accurate staging of local tumor extent and of distant metastases is necessary for evaluating the indications for surgical intervention. If histologic proof of malignancy of a pancreatic lesion is needed, different imaging techniques can be used for percutaneous biopsy of the tumor. Finally imaging is required in patients with a pancreatic tumor if an obstruction of the common bile duct is treated with palliative intent by endoscopy or transhepatic intervention. A rational and efficient selection from all the imaging techniques currently available requires a clear-cut definition of what is needed for surgical decision making in each individual case. Thereby one has to take into account whether the tumor arises from the exocrine or from the endocrine tissue of the pancreas.