Terpenes of Podocarpus lambertius

Sitosterol and the following terpenic compounds have been isolated from the bark of Podocarpus lambertius: 3β-hydroxytotarol, 4β-carboxynortotarol, and macrophyllic and lambertic acids. The leaves yielded sitosterol, stigmastan-3β,5α-diol-6-one, isopimaric acid, phyllocladene, isophyllocladene, 8,9-abieten-15-ol and 17-isophyllocladenol.     

The cytotoxic norditerpene dilactones of Podocarpus milanjianus and Podocarpus sellowii

The cytotoxic norditerpene dilactones nagilactone F and its new congener nagilactone G have been isolated from the bark constituents of Podocarpus milanjianus and Podocarpus sellowii. The diterpenes totarol, 19-oxototarol and macrophyllic acid were also isolated.     

Mechanisms of TNF-alpha stimulation of amiloride-sensitive sodium transport across alveolar epithelium

Because tumor necrosis factor (TNF)-alpha can upregulate alveolar fluid clearance (AFC) in pneumonia or septic peritonitis, the mechanisms responsible for the TNF-alpha-mediated increase in epithelial fluid transport were studied. In rats, 5 microg of TNF-alpha in the alveolar instillate increased AFC by 67%. This increase was inhibited by amiloride but not by propranolol. We also tested a triple-mutant TNF-alpha that is deficient in the lectinlike tip portion of the molecule responsible for its membrane conductance effect; the mutant also has decreased binding affinity to both TNF-alpha receptors. The triple-mutant TNF-alpha did not increase AFC. Perfusion of human A549 cells, patched in the whole cell mode, with TNF-alpha (120 ng/ml) resulted in a sustained increase in Na(+) currents from 82 +/- 9 to 549 +/- 146 pA (P < 0.005; n = 6). The TNF-alpha-elicited Na(+) current was inhibited by amiloride, and there was no change when A549 cells were perfused with the triple-mutant TNF-alpha or after preincubation with blocking antibodies to the two TNF-alpha receptors before perfusion with TNF-alpha. In conclusion, although TNF- alpha can initiate acute inflammation and edema formation in the lung, TNF-alpha can also increase AFC by an amiloride-sensitive, cAMP-independent mechanism that enhances the resolution of alveolar edema in pathological conditions by either binding to its receptors or activating Na(+) channels by means of its lectinlike domain.     

Alveolar epithelial fluid transport can be simultaneously upregulated by both KGF and beta-agonist therapy.

Although keratinocyte growth factor (KGF) protects against experimental acute lung injury, the mechanisms for the protective effect are incompletely understood. Therefore, the time-dependent effects of KGF on alveolar epithelial fluid transport were studied in rats 48-240 h after intratracheal administration of KGF (5 mg/kg). There was a marked proliferative response to KGF, measured both by in vivo bromodeoxyuridine staining and by staining with an antibody to a type II cell antigen. In controls, alveolar liquid clearance (ALC) was 23 +/- 3%/h. After KGF pretreatment, ALC was significantly increased to 30 +/- 2%/h at 48 h, to 39 +/- 2%/h at 72 h, and to 36 +/- 3%/h at 120 h compared with controls (P < 0.05). By 240 h, ALC had returned to near-control levels (26 +/- 2%/h). The increase in ALC was explained primarily by the proliferation of alveolar type II cells, since there was a good correlation between the number of alveolar type II cells and the increase in ALC (r = 0.92, P = 0.02). The fraction of ALC inhibited by amiloride was similar in control rats (33%) as in 72-h KGF-pretreated rats (38%), indicating that there was probably no major change in the apical pathways for Na uptake in the KGF-pretreated rats at this time point. However, more rapid ALC at 120 h, compared with 48 h after KGF treatment, may be explained by greater maturation of alpha-epithelial Na channel, since its expression was greater at 120 than at 48 h, whereas the number of type II cells was the same at these two time points. beta-Adrenergic stimulation with terbutaline 72 h after KGF pretreatment further increased ALC to 50 +/- 7%/h (P < 0.5). In summary, KGF induced a sustained increase over 120 h in the fluid transport capacity of the alveolar epithelium. This impressive upregulation in fluid transport was further enhanced with beta-adrenergic agonist therapy, thus providing evidence that two different treatments can simultaneously increase the fluid transport capacity of the alveolar epithelium.     

Alveolar and lung liquid clearance in anesthetized rabbits

Alveolar and lung liquid clearance were studied over 8 h in intact anesthetized ventilated rabbits by instillation of either isosmolar Ringer lactate (2 ml/kg) or autologous plasma (2 or 3 ml/kg) into one lower lobe. The half time for lung liquid clearance of the isosmolar Ringer lactate was 3.3 h and that for plasma clearance was 6 h. In the plasma experiments, the alveolar protein concentration after 1 h was 5.2 +/- 0.8 g/dl, which was significantly greater than the initial instilled protein concentration of 4.3 +/- 0.7 g/dl (P less than 0.05). Thus alveolar protein concentration increased by 21 +/- 12% over 1 h, which matched clearance from the entire lung of 19 +/- 11% of the instilled volume. Overall the rate of alveolar and lung liquid clearance in rabbits was significantly faster than in prior studies in dogs and sheep. The fast alveolar liquid clearance rate in rabbits was not due to higher endogenous catecholamine release, because intravenous and alveolar (5 x 10(-5) M) propranolol did not slow the clearance. Also, beta-adrenergic therapy with alveolar terbutaline (10(-5) or 10(-4) M) did not increase the alveolar or lung liquid clearance rates. Phloridzin (10(-3) M) did not slow alveolar liquid clearance. However, amiloride (10(-4) M) inhibited 75% of the basal alveolar liquid clearance in rabbits, thus providing evidence that alveolar liquid clearance in rabbits depends primarily on sodium-dependent transport. This rabbit study provides further evidence for important species differences in the basal rates of alveolar liquid and solute clearance as well as the response to beta-adrenergic agonists and ion transport inhibitors.     

13C NMR spectral analysis of lignans from Araucaria angustifolia

Pinoresinol dimethyl ether, secoisolariciresinol, lariciresinol, isolariciresinol and isolariciresinol-4′-methyl ether were isolated from the knots of dead trees of Araucaria angustifolia. The ¹³C NMR spectra of these compounds, their methyl and acetyl derivatives, and the corresponding one of matairesinol, have been recorded and the signals assigned. On the basis of these assignments, the structure of the new monomethyl ether of isolariciresinol has been established.