To evaluate the role of endothelin (ET) receptors in ET-1-induced pulmonary vasoreactivity, we studied the effects of ET-receptor agonists and antagonists in isolated perfused rat lungs. ET-1 (1-10 nM) caused concentration-dependent pulmonary vasoconstriction and gross pulmonary edema at a concentration of 10 nM. The combination of the selective ETA antagonist BQ-123 and the selective ETB antagonist BQ-788 inhibited ET-1-induced pulmonary vasoconstriction more effectively than BQ-123 alone, whereas BQ-788 alone enhanced the constriction. ET-1-induced hydrostatic pulmonary edema was prevented by the combination of BQ-123 and BQ-788 but not by either BQ-123 or BQ-788 alone. After the addition of 125 ng of exogenous ET-1, the perfusate levels of ET-1 were significantly higher in BQ-788-treated lungs than in either the vehicle control or BQ-123-treated lungs. The selective ETB agonist IRL-1620 also caused pulmonary vasoconstriction and edema, both of which were completely inhibited by BQ-788. ET-1-induced transient vasodilation was abolished by BQ-788 but was unaffected by BQ-123. These results suggest that in the isolated perfused rat lung, ET-1-induced vasoconstriction is mediated by both ETA and ETB receptors, whereas ET-1-induced transient vasodilation is mediated exclusively by the ETB receptor. Blockade of ETB receptors may result in enhanced ET-1 activity (via the ETA receptor) through inhibition of the ETB-mediated clearance of ET-1. Thus combined ETA and ETB blockade is required for the complete inhibition of ET-1-induced vasoconstriction in the rat pulmonary circulation.

The modulating effects of dietary feeding of two xanthophylls, astaxanthin (AX) and canthaxanthin (CX) during the postinitiation phase on colon carcinogenesis initiated with azoxymethane (AOM) were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks and then they were fed the diets containing AX or CX at concentrations of 100 and 500 p.p.m. for 34 weeks. The others contained the groups of rats treated with AX or CX alone and untreated. At the end of the study (week 37), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM and followed by AX or CX containing diet at a high dose (500 p.p.m.) were significantly smaller than those of rats given AOM alone (P < 0.001). In addition, AX or CX feeding significantly inhibited the development of aberrant crypt foci induced by AOM. Dietary exposure to AX or CX also decreased cell proliferation activity as revealed by measuring 5'-bromodeoxyuridine-labeling index as crypt cells, colonic mucosal ornithine decarboxylase activity and blood polyamine levels. These results indicate that AX and CX are possible chemopreventers for carcinogenesis of colon in addition to urinary bladder and oral cavity and such effects may be partly due to suppression of cell proliferation.

The results from this study provide further evidence for the role of circulating fibrocytes in fibrotic lung diseases.

The effect of a xanthine oxidase inhibitor, 1′‐acetoxychavicol acetate (ACA), on 4‐nitroquinoline 1‐oxide (4‐NQO)‐induced oral carcinogenesis was investigated in male F344 rats. All rats except those in the ACA‐alone and untreated groups were given 4‐NQO (20 ppm) in the drinking water for 8 weeks to induce oral cancer. Starting 1 week before the 4‐NQO exposure, animals were fed diet containing 100 ppm or 500 ppm ACA for 10 weeks, followed by the basal diet without ACA for 22 weeks. Other groups were fed the diet containing ACA at 100 ppm or 500 ppm for 22 weeks, starting 1 week after the cessation of 4‐NQO exposure. The remaining groups consisted of rats given 500 ppm ACA alone or untreated rats. At the termination of the experiment (32 weeks), the incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated in terms of 5‐bromodeoxyuridine (BrdU)‐labeling index and by morphometric analysis of silver‐stained nucleolar organizer regions’ protein (AgNORs) were compared among the groups. Feeding of ACA at the two doses during initiation or postinitiation significantly decreased the development of tongue carcinoma (93–100% reduction, P< 0.001) and preneoplasia (43–50% reduction for hyperplasia and 34–48% reduction for dysplasia, P<0.05). There were no such lesions in rats fed ACA alone or those in the untreated control group. The number of AgNORs per cell nucleus was significantly decreased by feeding of ACA at a high dose (500 ppm) (29% inhibition, P<0.05). The BrdU‐labeling index was also reduced by dietary administration of ACA (23–32% inhibition, P<0.01). In addition, ACA feeding reduced tongue polyamine levels (35–40% inhibition, P<0.05). These results indicate that ACA inhibited rat oral carcinogenesis, and such inhibition might be related to suppression of cell proliferation in the oral mucosa by the xanthine oxidase inhibitor.

By high-pressure Brillouin spectroscopy, sound velocities for all directions and three elastic constants of cubic ice VII have been determined up to 8 GPa at room temperature, with in situ identification of the orientation of the ice VII single crystal grown in a diamond-anvil cell. We have found the unusual result that the Cauchy relation (C» = C44) holds at every pressure for ice VII. This result suggests that the interactions between the atoms can be described by central forces. By a force-constant analysis of elastic constants, we show that the self-clathrate structure of two diamond-type sublattices can induce effectively central forces, and discuss their broad stability fields in the ice VII phase. PACS numbers: 78.35.+ c, 62.50.+ p, 62.65. +k, 64.70.KbThe behavior of H20 ice at high pressure is of fundamental importance in condensed matter and planetary science. An interesting variety of ice polymorphism exists under different conditions of pressure and temperature [1]. At room temperature, compression of liquid water leads to a tetragonal ice VI phase at pressures above 1.05 GPa and further to a cubic ice VII phase above 2. 1 GPa. However, above this pressure the phase diagram simplifies down to only two VII and VIII phases. In these higher-pressure phases, high density is achieved by forming "self-clathrate" structures [1 -4]. The structure of ice VII can be built up, as shown in Fig. 1, from two interpenetrated but unconnected diamond-type (ice I,) sublattices of oxygen atoms, where the oxygen atoms form a body-centered cubic (bcc) lattice and the protons are disordered within Pauling s ice rules (ice VIII is the protonordered form of ice VII). A further feature of ice VII that is related to the unconnected sublattices is that only four of the eight nearest-neighbor oxygen atoms are hydrogen bonded to the central oxygen atom.For pressure-induced H20 ice at pressures above 1.05 GPa and 300 K, Polian and Grimsditch [5,6] measured the Brillouin spectra only at a scattering geometry of 180 and observed the pressure dependence of nv in ices VI and VII up to 67 GPa without identification of the crystal orientation, where nv is the product of the refractive index and the sound velocity, respectively [see Eq. (3)]. From the pressure dependence of nv, they observed the VI VII phase transition at about P = 2. 1 GPa, and moreover claimed the possible existence of a symmetric ice X phase above 44 GPa. Around this region, however, Pruzan, Chervin, and Canny [7] have found no evidence of ice X in the Raman spectra, and Hemley et al. [8] have indicated from a synchrotronx-ray diffraction investigation that the bcc oxygen sublattice of ice VII persists to 128 GPa. Therefore, ice VII has a broad stability field at room temperature.Elastic properties determined by high-pressure Brillouin scattering [9] shed new light on the characteristic behavior of polymorphic varieties of ice, and provide some insight into the forces of interaction. The sound velocity for the probed acoustic phonon, which can be determined from the me...