scholarly journals Reproducing prolonged time to peak bisoprolol concentration by PBPK modeling with lysosomal trapping in enterocytes

Author(s):  
Dan‐Na Wu ◽  
Guo Yu ◽  
Guo‐Fu Li
1995 ◽  
Vol 268 (6) ◽  
pp. H2396-H2204 ◽  
Author(s):  
A. M. Shah ◽  
H. S. Silverman ◽  
E. J. Griffiths ◽  
H. A. Spurgeon ◽  
E. G. Lakatta

Previous studies in isolated cardiac myocytes suggest that impaired relaxation during reoxygenation after brief hypoxia results from abnormal Ca(2+)-myofilament interaction. Recent studies indicate that guanosine 3',5'-cyclic monophosphate (cGMP)-elevating interventions selectively enhance myocardial relaxation. We investigated the effect of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) on posthypoxic relaxation in single rat myocytes, with simultaneous measurement of contraction and intracellular Ca2+ (indo 1 fluorescence). In control myocytes (n = 11), reoxygenation after 10 min of hypoxia markedly prolonged time to peak shortening (+36.5 +/- 4.2%) and half-relaxation time (+75.7 +/- 11.3% cf. normoxic values; both P < 0.001) and reduced diastolic length but did not change cytosolic Ca2+. Under normoxic conditions, 50 microM 8-BrcGMP slightly reduced time to peak shortening and half-relaxation time and increased diastolic length but did not alter cytosolic Ca2+. In the presence of 8-BrcGMP, there was no posthypoxic delay in twitch relaxation nor was there a decrease in diastolic length (half-relaxation time -5.8 +/- 3.3% cf. normoxic values; P < 0.05 cf. control group; n = 11). Cytosolic Ca2+ remained unaltered. Thus, 8-BrcGMP fully prevents impaired posthypoxic relaxation in isolated cardiac myocytes, probably by altering Ca(2+)-myofilament interaction.


VASA ◽  
2010 ◽  
Vol 39 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Schubert

The subclavian steal effect indicates atherosclerotic disease of the supraaortic vessels but rarely causes cerebrovascular events in itself. Noninvasive imaging providing detailed anatomic as well as hemodynamic information would therefore be desirable. From a group of 25 consecutive patients referred for MR angiography, four with absent or highly attenuated signal in one of the vertebral arteries on 3D multislab time-of-flight MR angiography were selected to undergo 3D time-resolved contrast-enhanced MR angiography. The time-resolved 3D contrast series (source images and MIPs) were evaluated visually and by graphic analysis of time-intensity curves derived from the respective V1 and V3 segments of both vertebral arteries on the source images. In two cases with high-grade proximal left subclavian stenosis, time-resolved 3D ce-MRA was able to visualise retrograde contrast filling of the left VA. There was a marked delay in time-to-peak between the left and right V1 segments in one case and a shallower slope of enhancement in another. In the other two cases, there was complete or collateralised segmental occlusion of the VAs.


1991 ◽  
Vol 30 (05) ◽  
pp. 183-188
Author(s):  
A. Aydrner ◽  
A. Oto ◽  
E. Oram ◽  
O. Gedik ◽  
C. F. Bekdik ◽  
...  

Left ventricular function including regional wall motion (RWM) was evaluated by 99mTc first-pass and equilibrium gated blood pool ventriculography and glycohemoglobin (HbA1c) blood levels determined by a quantitative column technique in 25 young patients with insulin-dependent diabetes mellitus without clinical evidence of heart disease, and in healthy controls matched for age and sex. Phase analysis revealed abnormal RWM in 19 of 21 diabetic patients. The mean left ventricular global ejection fraction, the mean regional ejection fraction and the mean 1/3 filling fraction were lower and the time to peak ejection, the time to peak filling and the time to peak ejection /cardiac cycle were longer in diabetics than in controls. We found high HbA1c levels in all diabetics. There was no significant difference between patients with and without retinopathy and with and without peripheral neuropathy in terms of left ventricular function and HbA1c levels.


1987 ◽  
Vol 26 (05) ◽  
pp. 206-211 ◽  
Author(s):  
P. Knesewitsch ◽  
N. H. Göldel ◽  
S. Fritsch ◽  
E. Moser

Results of 606 equilibrium radionuclide ventriculographies (ERNV) performed in 348 non-selected patients receiving Adriamycin (ADM) therapy were stored in a data base system. The aim of the study was to assess the influence of a potential cardiotoxic therapy on left ventricular pump function. Increasing ADM doses yielded a significant (p <0.05) decrease of the resting ejection fraction (R-gEF), the peak ejection rate and the peak filling rate. Enddiastolic and endsystolic volumes increased significantly. Stroke volume, heart rate and time to peak filling rate did not change significantly. 368 follow-up studies were performed in 128 patients: 65/128 patients presented a decrease of R-gEF, but only in 45 of these patients R-gEF values fell into the pathologic range. In 44 of these follow-ups, R-gEF remained unchanged. In 19 patients, a R-gEF increase was observed. At the beginning of ADM therapy 14% of the patients had subnormal R-gEF values. With increasing ADM doses pathologic findings increased to 86% in patients with ADM doses higher than 500 mg/m2.


2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
O Zaro Weber ◽  
J Sobesky ◽  
FG Lehnhardt ◽  
V Hesselmann ◽  
M Frackowiak ◽  
...  
Keyword(s):  

2020 ◽  
Vol 16 (6) ◽  
pp. 619-627
Author(s):  
Elisa Cipponeri ◽  
Cesare Blini ◽  
Christian Lamera ◽  
Valentina De Mori ◽  
Giovanni Veronesi ◽  
...  

Background : There is no data available on the best insulin treatment to counteract the effects of glucose excursions due to a moderate alcohol intake associated with portions of slight fat and protein-containing food, as often the case during social happenings or “happy hours”. Introduction: This study analyzes the glycemic control and quality of life in 8 adult type 1 diabetic (T1D) patients on insulin-pump therapy which were invited to consume a traditional Italian aperitif (“Spritz” and chips). Introduction : This study analyzes the glycemic control and quality of life in 8 adult type 1 diabetic (T1D) patients on insulin-pump therapy which were invited to consume a traditional Italian aperitif (“Spritz” and chips). Methods: Patients consumed Spritz aperitif twice: using their habitual bolus, based on carbohydrates (CHO) counting (V1), or with a personalized, advanced bolus (V2) calculated from insulin/Kcal derived from Fats and Proteins (FPU). Post-prandial glucose was continuously monitored; glucose incremental areas (iAUC), glucose peak and time to peak, and estimated change from V1 to V2 from repeated- measures models were computed. Each patient fulfilled validated questionnaires on quality of life, knowledge about diabetes and CHO counting. Results : After the educational program, a reduced iAUC (0-80 min: -306, p=ns; 40-80 min: -400, p=0.07) due to greater (p=0.03) and prolonged double-wave insulin boluses was observed. Blood glucose peak and time to peak were also reduced. Moreover, improvements in the psycho-affective dimension, as well as in the alimentary knowledge were detected. Conclusion: Therefore, a personalized educational program on CHO + FPU counting together with insulin bolus management can improve glycemic control during social consumption of alcohol, with positive reflections on the psycho-affective dimension. Further studies are mandatory to confirm such preliminary results.


2021 ◽  
Author(s):  
Mistaya Langridge ◽  
Ed McBean ◽  
Hossein Bonakdari ◽  
Bahram Gharabaghi

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