Data from Single Photon Emission Computed Tomography (SPECT) studies are blurred by inevitable physical phenomena occurring during data acquisition. These errors may be compensated by means of ...reconstruction algorithms which take into account accurate physical models of the data acquisition procedure. Unfortunately, this approach involves high memory requirements as well as a high computational burden which cannot be afforded by the computer systems of SPECT acquisition devices. In this work the possibility of accessing High Performance Computing and Networking (HPCN) resources through a World Wide Web interface for the advanced reconstruction of SPECT data in a clinical environment was investigated. An iterative algorithm with an accurate model of the variable system response was ported on the Multiple Instruction Multiple Data (MIMD) parallel architecture of a Cray T3D massively parallel computer. The system was accessible even from low cost PC-based workstations through standard TCP/IP networking. A speedup factor of 148 was predicted by the benchmarks run on the Cray T3D. A complete brain study of 30 (64×64) slices was reconstructed from a set of 90 (64×64) projections with ten iterations of the conjugate gradients algorithm in 9 s which corresponds to an actual speed-up factor of 135. The technique was extended to a more accurate 3D modeling of the system response for a true 3D reconstruction of SPECT data; the reconstruction time of the same data set with this more accurate model was 5 min. This work demonstrates the possibility of exploiting remote HPCN resources from hospital sites by means of low cost workstations using standard communication protocols and an user-friendly WWW interface without particular problems for routine use.
Bradykinin (BK) is a vasoactive peptide reputed to play an important role in cardiovascular homeostasis. In this study, we describe the cardiovascular changes (mean blood pressure (BP) and heart rate ...(HR)) induced by the i.v. administration (left jugular vein) of two selective kinin B
2
receptor antagonist, namely icatibant (0.11 µmol/kg as a bolus) and MEN11270 (0.11 µmol/kg as a bolus or 1 µmol/kg infused in 15 or 60 min), in urethane-anaesthetized or conscious rats with an indwelling catheter implanted in the right carotid artery for BP measurements. In conscious rats, icatibant at 0.1 or 0.3 µmol/kg did not change BP but at 0.1 µmol/kg increased HR at 30 min from administration. MEN11270 at 0.1 or 0.3 µmol/kg induced a dose-related increase in BP and a concomitant bradycardia (significant at 0.3 µmol/kg) lasting for 5 or 30 min, respectively. Icatibant at 1 µmol/kg induced a slight (P < 0.05) increase in BP that resolved in 5 min and a biphasic tachycardia (peaks at 30 and 90 min from administration). MEN11270 at 1 µmol/kg induced a triphasic change in HR (tachycardia in the first 5 min, bradycardia at 30 min, and tachycardia at 90 and 120 min) and a biphasic change in BP (hypotension at 15 min and hypertension at 30 min). The i.v. infusion of MEN11270 (1 µmol/kg in 15 or 60 min) produced hypertension, whereas HR was increased only following the 15-min infusion. In urethane-anaesthetized rats, both icatibant and MEN11270 (0.1 µmol/kg as a bolus) increased BP and the onset for this effect was correlated with the time course of the antagonism of BK-induced hypotension, where the effect of MEN11270 was more rapid than that of icatibant. These results indicate that kinin B
2
receptor antagonists can induce acute cardiovascular effects, and the reason for the different haemodynamic profile between icatibant and MEN11270 could be putatively attributed to kinetic characteristics.Key words: icatibant, MEN11270, bradykinin, blood pressure, heart rate.
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Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
1
The effects of intravenous captopril and enalaprilic acid on the increase in pulmonary inflation pressure induced by different bronchoconstrictor agents were evaluated in the anaesthetized ...guinea‐pig.
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Captopril and enalaprilic acid (1.6–200 μg kg−1) enhanced dose‐dependently the bronchoconstriction (BC) induced by substance P. The threshold effective dose was 1.6 μg kg−1 and maximal potentiation over the control response was more than 400% for both agents. Enalaprilic acid was also assayed for serum and lung angiotensin converting enzyme (ACE) inhibition in anaesthetized guinea‐pigs. This drug produced a dose‐dependent inhibition of ACE in both tissues, with ED50 s of 7.6 and 9.4 μg kg−1, respectively: this inhibitory activity was positively correlated to substance P potentiation.
3
Captopril (8–1000 μg kg−1) enhanced dose‐dependently the BC induced by capsaicin. The threshold effective dose was 40 μg kg−1 and maximal potentiation about 90%.
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Captopril (200–1000 μg kg−1) did not affect BC induced by bradykinin. However, this response was markedly enhanced (about 200%) by captopril 200 μg kg−1 in propranolol‐pretreated animals.
5
Captopril and enalaprilic acid (200–1000 μg kg−1) slightly (20–40%) but significantly enhanced the BC induced by 5‐hydroxytryptamine. However, this response was potentiated to the same extent by a dose of prazosin, which produced a degree of hypotension similar to that observed after administration of the ACE inhibitors.
6
In conclusion, ACE inhibitors potentiate the BC induced by substance P and, to a minor extent, that induced by capsaicin in the anaesthetized guinea‐pig. Potentiation of substance P is well correlated with ACE inhibition in guinea‐pig serum and lungs. These experimental results may offer a mechanistic interpretation of cough and bronchial hyperreactivity observed in patients receiving treatment with ACE inhibitors.
3HMEN 11420, a radiolabeled glycosylated peptide antagonist of the tachykinin NK2 receptor, has been investigated in ligand-receptor binding assays using membranes of CHO cells transfected with the ...human tachykinin NK2 receptor. 3HMEN 11420 bound to a single class of high affinity binding sites: its binding was inhibited by natural tachykinins (potency ranking: NKA >> SP > or = NKB), as well as by peptide (MEN 11420 > MEN 10376 >> R 396) and nonpeptide (SR 48968 > GR 159897) selective NK2 receptor antagonists. These data indicate that 3HMEN 11420 is a potent radioligand for the human tachykinin NK2 receptor that may represent a useful tool for studying ligand-receptor interactions at the molecular level.
All patients hospitalized between May 1987 and June 1988 suffering from burns covering over 50 per cent of the body surface area were treated by topical application of a cream containing cerium ...nitrate (0.05 M) and silver sulphadiazine (0.03 M) (CN + SSD). Eleven patients were included in this series, with a mean age of 35 years (range 22-65), a mean total burn size of 78 per cent (range 50-96 per cent) and full skin thickness covering a mean of 48 per cent (range 10-91 per cent). Eight patients survived (73 per cent) (mean age 36 years; mean total burn surface 73 per cent; mean full skin thickness burn surface, 38 per cent). These results are far better than those obtained in our Unit where a survival rate of 34 per cent was obtained in a comparable series of patients treated before 1987. Sixty positive blood cultures were obtained, which included a large variety of organisms with a slight predominance of Staph. aureus, Candida albicans and Ps. aeruginosa. Wound cultures were positive in 72 per cent of swabs and showed a predominance of Ps. aeruginosa (59 per cent of all the strains isolated). Even if CN + SSD appears in this series not to be very efficient in preventing wound colonization and septic complications, it permitted a very high survival rate in the treated patients, taking into account the extreme severity of the injuries. This beneficial effect is probably the consequence of the protective action of the yellow-green eschar formed by CN + SSD.
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1 The pharmacological profile of LR‐B/081, (methyl 2‐4‐butyl‐2‐methyl‐6‐oxo‐5‐2′‐(1H‐tetrazol‐5‐yl)1,1′‐biphenyl‐4‐ylmethyl‐1(6H)‐pyrimidinylmethyl‐3‐thiophenecarboxylate), a novel antagonist at the ...angiotensin II (AII) AT1‐receptor, was studied in vitro and in vivo.
2 In rabbit aortic strips incubated with LR‐B/081 (1–1,000 nm), the concentration‐response curve to AII was displaced to the right in a nonparallel fashion and the maximal contraction was progressively reduced, indicating that the compound is an insurmountable antagonist in this preparation (apparent pKB = 9.50 ± 0.23). However, the interaction of LR‐B/081 with AII receptors was found to be reversible, since the maximal response to AII was restored by coincubation with losartan, a surmountable AII AT1‐antagonist. Contractions elicited by KCl or phenylephrine were not affected by 10 μm LR‐B/ 081.
3 In rat isolated perfused kidney, LR‐B/081 and losartan antagonized the AII‐induced vasoconstriction IC50 (95% confidence limits) = 17(13–24) and 39(32–54) nm, respectively. The LR‐B/081 antagonism was incompletely reversed by excess AII, while losartan was fully displaced. The IC50 values of LR‐B/081 and losartan obtained against vasoconstriction induced by endothelin‐1 and noradrenaline were two orders of magnitude higher.
4 In pithed rats, the intravenous administration of LR‐B/081 (0.2–2 μmol kg−1) dose‐dependently shifted to the right in a nonparallel fashion the dose‐pressor response curve to AII. The maximal pressor response to AII was reduced by LR‐B/081 in a dose‐dependent fashion. The coadministration of losartan induced a progressive recovery of the maximal pressor response to AII, indicating that in vivo the interaction of LR‐B/081 with AII receptors is reversible. LR‐B/081 at 6 μmol kg−1, i.v. also did not affect the vasopressor response induced by noradrenaline in the pithed rat.
5 In conscious normotensive rats, single oral administration of LR‐B/081 at 6 μmol kg−1 markedly inhibited the AII‐induced pressor response; the inhibition lasted more than 24 h.
6 In conscious renal hypertensive rats, intravenous LR‐B/081 appeared as potent as losartan (ED40mmHg (95% confidence limits) = 0.50(0.36–0.70) and 0.86(0.57–1.3) μmol kg−1, respectively). A single intravenous (2 μmol kg−1) or oral (6 μmol kg−1) administration of LR‐B/081 induced a marked fall in blood pressure which lasted for at least 12 h.
7 In conscious spontaneously hypertensive rats, LR‐B/081 at 20 μmol kg−1, p.o., induced a marked and sustained fall in blood pressure. The duration of the antihypertensive effect was longer than 12 h. Heart rate was not modified by LR‐B/081 treatment. Repeated oral administration of 17 μmol kg−1 LR‐B/081 for 16 days did not result in the development of tolerance.
8 These results demonstrate that LR‐B/081 is a potent, selective and orally active antagonist of AII at the AT1‐receptor subtype, which markedly lowers the blood‐pressure in conscious renal and spontaneously hypertensive rats.
The substitution reactions of VCp2(CO) with some selected olefins have been studied. Tetracyanoethylene (tcne) and fumaronitrile (fn), containing electron-withdrawing substituents, promptly react ...with VCp2(CO) with quantitative formation of VCp2(tcne) and VCp2(fn), respectively, while acrylonitrile and diethyl fumarate (defu) gave partial displacement of coordinated carbon monoxide under a CO atmosphere. No CO displacement from VCp2(CO) was observed with cyclooctene and norbornene. The carbonylation of VCp2(defu) (VCp2(defu) + CO ⇄ VCp2(CO) + defu) has been studied gas volumetrically from both sides, and the equilibrium constant for the displacement of coordinated defu by carbon monoxide was estimated to be 55 ± 8 at 298.5 K. Variable-temperature experiments between 298.5 and 327.7 K have shown the enthalpy change to be −2.4 kcal mol-1. The equilibrium constant for the addition of defu to VCp2 (VCp2 + defu ⇄ Cp2(defu)) has been evaluated spectroscopically to be 150 ± 11 at 298.5 K. From the available data, the equilibrium constant for the addition of carbon monoxide to VCp2 (VCp2 + CO ⇄ VCp2(CO)) has been calculated to be K a = (8.2 ± 0.4) × 103: i.e., about 2 orders of magnitude higher than that for the complexation of defu. The present data for the 3d3 system of vanadium(II) (ν̃CO in toluene 1881 cm-1) are compared with those exhibited by the 5d10 system of AuCl(CO) (ν̃CO in toluene 2153 cm-1), whose behavior consistently shows an opposite dependence, as far as the olefin/CO competition is concerned, on the nature of the olefin.
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![Characterization of [3H]MEN...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0006-291X/small "Characterization of [3H]MEN 11420, a novel glycosylated peptide antagonist radioligand of the tachykinin NK2 receptor")
