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71.
1 Adenosine 5'-triphosphate (ATP) is an enteric neurotransmitter which acts at purine receptors on intestinal nerve and muscle. This study set out to shed light on the receptor mechanisms by which exogenous and endogenous ATP influences intestinal peristalsis. 2 Peristalsis in isolated segments of the guinea-pig small intestine was triggered by a perfusion-induced rise of the intraluminal pressure. Motor changes were quantified by alterations of the peristaltic pressure threshold (PPT) at which propulsive muscle contractions were elicited. 3 ATP (>/= 3 microM) increased PPT and abolished peristalsis at concentrations of 100-300 microM. Adenosine 5'-O-2-thiodiphosphate (ADPbetaS, 3-100 microM) was more potent, whereas alpha,beta-methylene ATP (alpha,beta-meATP, 3-100 microM) was less potent, than ATP in depressing peristalsis. 4 8-Phenyltheophylline (10 microM) attenuated the anti-peristaltic effect of 10 and 30 microM ATP but not that of higher ATP concentrations. Apamin (0.5 microM) counteracted the ability of ATP, ADPbetaS and alpha,beta-meATP to enhance PPT. Suramin (300 microM) and pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 150 microM) antagonized the inhibitory effect of alpha,beta-meATP on peristalsis but did not alter the effect of ATP and ADPbetaS. 5 PPADS (50-150 microM) reduced PPT by as much as 50%. This stimulant effect on peristalsis was prevented by suramin (300 microM) but left unaltered by apamin (0.5 microM) and NG-nitro-L-arginine methyl ester (300 microM). 6 These data show that exogenous and endogenous ATP inhibits intestinal peristalsis via different apamin-sensitive purinoceptor mechanisms. Exogenous ATP depresses peristalsis mostly via suramin- and PPADS-insensitive P2 receptors, whereas endogenous purines act via P2 receptors sensitive to both suramin and PPADS. 相似文献
72.
Meibohm B Hochhaus G Möllmann H Barth J Wagner M Krieg M Stöckmann R Derendorf H 《Journal of pharmacokinetics and biopharmaceutics》1999,27(2):127-147
The suppression of endogenous cortisol release is one of the major systemic side effects of inhaled corticosteroids in the treatment of asthma. The circadian rhythm of the endogenous cortisol release and the resulting plasma concentrations as well as the release suppression during corticosteroid therapy could previously be described with an integrated PK/PD model. Based on this model, a PK/PD approach was developed to quantify and predict the cumulative cortisol suppression (CCS) as a surrogate marker for the systemic activity of inhaled corticosteroid therapy. The presented method was applied to predict CCS after single doses and during short-term multiple dosing of the inhaled corticosteroids flunisolide (FLU), fluticasone propionate (FP), and triamcinolone acetonide (TCA), and after oral methylprednisolone as systemic reference therapy. Drug-specific PK and PD parameters were obtained from previous single-dose studies and extrapolated to the multiple-dose situation. For single dosing, a similar CCS within the range of 16-21% was predicted for FP 250 micrograms, FLU 500 micrograms, and TCA 1000 micrograms. For multiple dosing, a respective CCS of 28-33% was calculated for FLU 500 micrograms bid, FP 250 micrograms, bid, and TCA 1000 micrograms bid. Higher cortisol suppression compared to these single and multiple dosing regimens of the inhaled corticosteroids was predicted after oral doses of only 1 mg and 2 mg methylprednisolone, respectively. The predictive power of the approach was evaluated by comparing the PK/PD-based simulations with data reported previously in clinical studies. The predicted CCS values were in good correlation with the clinically observed results. Hence, the presented PK/PD approach allows valid predictions of CCS for single and short-term multiple dosing of inhaled corticosteroids and facilitates comparisons between different dosing regimens and steroids. 相似文献
73.
P. Mialon L. Barthélémy 《Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid》1993,20(2):181-189
The effect of a previous exposure to hyperbaric oxygen (HBO) on the synthesis capacity of prostaglandin (PG) and thromboxane (TX) was investigated in the brain of male rats. Three groups of rats were used:
- Neurotoxic HBO (n = 11): The rats were exposed to sixfold the atmospheric pressure (101.3 kPa), i.e., 6 absolute atmospheres (ATA), of pure O2 up to the first convulsion (6 ATA O2);
- Mild hyperoxia (n = 10): The rats were exposed to compressed air at the same absolute pressure and for a similar time than that of the neurotoxic HBO group (here PO2 is 1.26 ATA);
- Normoxia at atmospheric pressure (PO2 is 0.21 ATA) for control.
74.
J Froelich K H Barth R J Lutz S V Lossef D Lindisch 《Journal of vascular and interventional radiology : JVIR》1992,3(4):713-718
Performance of 11 commercially available 4- and 5-F aortic flush catheters was evaluated with respect to the extent of upstream injection, catheter motion, and downstream homogeneity of a 10-, 15-, and 20-mL/sec bolus of 76% meglumine sodium diatrizoate at room temperature. Tests were made in a pulsatile aortic flow model containing circulating fluid isoviscous to blood. The injection process was recorded on videotape. Homogeneity of the contrast material bolus was determined spectrophotometrically from samples collected from the center and each of the four quadrants of the vessel lumen. Upstream contrast material injection between 1.5 and 7 cm in length emerged from all catheters; it was lowest with one of the "tennis racket" designs from one and a new spiral end-loop design (Halo) from another manufacturer. All catheters, except the most rigid and largest-caliber catheter (5.8 F) showed considerable shaft motion at the higher injection rates. Downstream contrast material mixing homogeneity was always best at the highest injection rate but altogether was better for the Halo catheter than for any other catheter tested. It is concluded that all tested 4- and 5-F aortic flush catheters show some undesirable features, but certain design modifications improve performance and comparative testing is helpful to distinguish such features. 相似文献
75.
Silent cerebral ischemia detected by diffusion-weighted MRI after carotid endarterectomy 总被引:6,自引:0,他引:6
Barth A Remonda L Lövblad KO Schroth G Seiler RW 《Stroke; a journal of cerebral circulation》2000,31(8):1824-1828
BACKGROUND AND PURPOSE: Small emboli arising from a friable plaque during carotid endarterectomy (CEA) constitute an important risk of perioperative ischemic complications. To evaluate the incidence and significance of silent cerebral ischemic lesions of embolic origin after CEA, we prospectively examined a series of surgical patients with high-grade carotid stenosis by using diffusion-weighted MRI (DWI). We also tried to correlate postoperative ischemic lesions with the occurrence of sonographic cerebral embolic signals, the presence of plaque ulcerations, and the use of intraoperative shunting. METHODS: Of a consecutive series of 53 patients undergoing elective CEA for high-grade carotid stenosis, 48 patients with unchanged postoperative neurological status were prospectively studied with DWI of the brain the day before and the day after the operation. The magnetic resonance images were analyzed by 2 neuroradiologists blinded to the clinical result of the operation. Any new hyperintense signal was interpreted as a postoperative ischemic lesion. RESULTS: Forty-six (95.8%) of 48 patients had unchanged postoperative brain DWI. In 2 patients (4.2%), a new single asymptomatic hyperintense signal was observed on the side of the operation. Both lesions were small and presumably of embolic origin. They were not related to sonographic embolic signals, plaque ulcerations, or intraoperative shunting. CONCLUSIONS: These results suggest that the incidence of silent ischemic brain lesions of embolic origin after CEA is low and does not correlate with the occurrence of intraoperative sonographic microemboli. They confirm that CEA is a safe procedure that carries a low risk of postoperative cerebral events. 相似文献
76.
Yang W Barth RF Bartus RT Rotaru JH Moeschberger ML Ferketich AK Nawrocky MM Coderre JA Goodman JH 《Neurosurgery》2000,47(1):189-97; discussion 197-8
77.
Zusammenfassung Befindlichkeitsstörungen ohne pathologischen Befund stellen einen nicht unerheblichen Anteil des internen Krankengutes dar. Ein zunehmender Teil der Patienten führt diese Beschwerden auf Einflüsse aus dem Bereich der Arbeitswelt oder Umwelt zurück. Mangels vorliegender Pathologie neigt die Schulmedizin dazu, diese Syndrome eher dem psychiatrischen Formenkreis zuzuordnen oder psychologische Konzepte in die Kausalitätsüberlegungen einzubeziehen. Medien wie Alternativmedizin unterstützen in diesem Themenbereich meist nicht die Konzepte der faktenorientierten Schulmedizin, sie halten Organschäden durch Belastungen mit Umweltnoxen für durchaus möglich, selbst wenn diese in zulässiger Höhe liegen. Postuliert wird häufig eine gesteigerte Individualempfindlichkeit. Beispiele solcher modern interpretierter Syndrome sind das Sick Building Syndrome, das chronische Erschöpfungssyndrom oder die idiopathische Umweltunverträglichkeit. Infolge der Unspezifität dieser Beschwerden ähnelt sich die Symptomatik, wenngleich diesen Syndromen durchaus unterschiedliche Konzepte zugrunde gelegt werden. Deshalb ist die Überlegung, es handle sich immer um das selbe Krankheitsbild, unberechtigt. Eine breite differenzialdiagnostische Palette ist gefordert, da es sich meist um Ausschlussdiagnosen handelt. Zur realitätsnahen Beurteilung sind fallweise auch Verfahren des Biomonitorings oder Ambientmonitorings heranzuziehen.
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78.
MJ Stevens PD Stricker J Saalfeld PC Brenner R Kooner GFA O'Neill PJ Duval RS Jagavkar P Cross J Martland 《Journal of Medical Imaging and Radiation Oncology》2003,47(2):152-160
Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability. 相似文献
79.
80.
Abril N; Luque-Romero FL; Prieto-Alamo MJ; Rafferty JA; Margison GP; Pueyo C 《Carcinogenesis》1997,18(10):1883-1888
Here we confirm and extend our previous studies demonstrating that the
mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is
markedly enhanced (not prevented) in bacteria expressing the O6-
alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli
ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt
ATase sensitizes the bacteria to the lethal effects of these carcinogens,
suggesting that one or more of the potentially mutagenic lesions induced by
DBE and DBM in the presence of Ogt has additional lethal capacity. We
further demonstrate that the sensitization to both lethality and
mutagenesis by DBE and DBM is a property shared by other DNA
alkyltransferases. This objective was accomplished by quantifying the
induction of mutations and lethal events in ogt- ada- E. coli expressing an
exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian
recombinant ATases enhanced the lethal and mutagenic actions of DBE and
suppressed the lack of sensitivity of the vector- transformed bacteria to
DBM. In most cases the order of effectiveness of the ATases ranked: murine
> human > Ogt > rat. Further comparisons included the full-length
Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the
O6-methylguanine binding domain of the protein. The full-length Ada ATase
was effective in enhancing the lethality but not the mutagenicity induced
by DBE and DBM. The T-ada ATase provided less sensitization than Ada to
lethality by DBE, but of the three bacterial ATases T-ada yielded the
highest sensitization to mutagenesis by this compound. T-ada and Ada ATases
were in general less effective than the mammalian versions, with the
exception of the rat recombinant ATase. The effectiveness of the different
mammalian and bacterial ATases in promoting the deleterious actions of
dibromoalkanes was compared with the effectiveness of these proteins in
suppressing the lethal and mutagenic effects induced by
N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and
mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase,
since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt-
ada- cells showed no effect, in spite of the reported potential of
bioactive dihaloethane- derived species to alkylate Trx.
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