Krzysztof Jonderko

Effect of nifedipine on interdigestive gallbladder volume and postprandial gallbladder emptying in man

The effect of two oral doses (10 and 20 mg) of nifedipine versus placebo on the fasted gallbladder volume and on the meal-induced gallbladder emptying was assessed according to a double-blind study protocol in 12 healthy volunteers. Eight subjects underwent three studies (with placebo and with both nifedipine doses), whereas in two subjects the effect of a 10-mg nifedipine dose, vs placebo and in two others the effect of a 20-mg nifedipine dose vs placebo was examined. The studies were performed on separate days, and the gallbladder volume was measured by means of real-time ultrasonography. Neither placebo nor 20 mg nifedipine per os elicited any significant change in the fasted gallbladder vlume. With 10 mg nifedipine per os a significant increase in the interdigestive gallbladder volume was observed: 22.9±2.9 cm3 before and 26.2±3.2 cm3 after the drug receipt (P<0.005). A trend towards an inhibition of the postprandial gallbladder emptying was observed with 10 mg nifedipineper os without, however, reaching the level of statistical significance. Following 20 mg nifedipineper os, a marked delay in the meal-stimulated gallbladder emptying occurred as reflected by a decrease in the gallbladder ejection fraction from 48.1±4.5% (placebo) to 26.4±5.0% (nifedipine) (P<0.02) at 30 min and from 54.0±3.6% (placebo) to 33.2±4.6% (nifedipine) (P<0.02) at 40 min after the test meal. We conclude that a therapeutic oral dosage of nifedipine has a significant relaxing effect on the human gallbladder.

13C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations

AIM To find the most reproducible quantitative parameter of a standard (13)C-methacetin breath test ((13)C-MBT). METHODS Twenty healthy volunteers (10 female, 10 male) underwent the (13)C-MBT after intake of 75 mg (13)C-methacetin p.o. on three occasions. Short- and medium-term reproducibility was assessed with paired examinations taken at an interval of 2 and 18 d (medians), respectively. RESULTS The reproducibility of the 1-h cumulative (13)C recovery (AUC(0-60)), characterized by a coefficient of variation of 10%, appeared to be considerably better than the reproducibility of the maximum momentary (13)C recovery or the time of reaching it. Remarkably, as opposed to the short gap between consecutive examinations, the capacity of the liver to handle (13)C-methacetin increased slightly but statistically significantly when a repeat dose was administered after two to three weeks. Regarding the AUC(0-60), the magnitude of this fixed bias amounted to 7.5%. Neither the time gap between the repeat examinations nor the gender of the subjects affected the (13)C-MBT reproducibility. CONCLUSION (13)C-MBT is most reproducibly quantified by the cumulative (13)C recovery, but the exactitude thereof may be modestly affected by persistent stimulation of CYP1A2 on repeat examinations.

Real-time ultrasonography as a noninvasive tool for the examination of canine gallbladder emptying: A validation study

An ultrasonographic measurement of the gallbladder volume based on an ellipsoid approximation of the gallbladder shape was validated in vivo in the dog. The mean difference between the ultrasonographically determined and the true gallbladder volumes amounted to 2.0 +/- 1.6 cm3 (mean +/- SD), whereas the regression line computed for the ultrasonographically measured versus true gallbladder volumes was y = 0.892x + 3.0, r = 0.955, p much less than 0.001. The ultrasonographic method enabled a noninvasive, repetitive measurement of either a meal- or caerulein-induced gallbladder emptying in the dog.

Noninvasive evaluation of kinetics of gallbladder emptying and filling in the dog: A real-time ultrasonographic study

Patterns of gallbladder contraction induced by a meal or cerulein were examined by means of real-time ultrasonography in conscious dogs. The postprandial gallbladder emptying was characterized by two parameters of the power-exponential function: the gallbladder half emptying timeT1/2=47.3 ± 4.7 min and the curve shape paremeterS=0.866 ± 0.036. Cerulein infused at stepwise increasing rates of 0.7, 2.2, 7.4, 22.2, and 66.5 pmol/kg/hr, administered each for 10 min, evoked a gallbladder contraction to 87.4 ± 3.8%, 66.7 ± 2.4%, 44.5 ± 1.5%, 25.9 ± 2.1%, and 11.9 ± 2.0% of the basal volume, respectively. The dependence of the gallbladder emptying on the dose of cerulein was described by the equation of linear regressiony −21.33 [ln(dose + 1)] + 95.81 (r=−0.963,P<0.001). Accordingly, the cerulein dose required to evoke a 50% reduction of the gallbladder volume amounted to 7.6 pmol/kg/hr (95% confidence interval: 6.8–8.6 pmol/kg/hr). A plateau at the level of about 44% of the basal gallbladder volume characterized the time-course of the gallbladder emptying between 20 and 60 min of the infusion at a constant rate of 7.4 pmol/kg/hr. On the other hand, the 1-hr infusion of 22.2 pmol/kg/hr evoked a continuous decrease in the gallbladder volume with a nadir of 10.2 ± 0.7% achieved at 60 min. Refilling of the gallbladder, contracted after a 1-hr infusion of cerulein, was complete within 30 and 60 min after the end of infusion for rates of 7.4 pmol/kg/hr and 22.2 pmol/kg/hr, respectively. The time course of the gallbladder filling after cessation of 1-hr infusion of cerulein at 7.4 pmol/kg/hr was described by the equation of linear regression of relative gallbladder volumes vs time:y=1.732x + 48.61 (r=0.739,P < 0.001). Refilling of the gallbladder was faster during the first 30 min (y=2.191x+7.13,r=0.885,P<0.001) and slower between 30 and 60 min (y=1.218x + 74.97,r=0.533,P < 0.001) after the end of a 1-hr infusion of cerulein at a rate of 22.2 pmol/kg/hr.

Impact of combined oral contraceptives containing ethinylestradiol on the liver microsomal metabolism

Abstract Objectives To check whether currently used combined oral contraceptives (COCs) containing ethinylestradiol (EE) affect the liver microsomal metabolism. Methods 13C-methacetin breath test (13C-MBT) – a sensitive non-invasive probe of cytochrome P-450 1A2 activity – was performed in 15 women on day 14, 15, 16, 17 or 18 of intake of their COC (containing EE), and between day 1 and 5 during the withdrawal bleeding, as well as in nine women not using hormonal contraception during the luteal phase of their cycle (between the 17th and the 23rd day), and between day 1 and 5 during menstruation. Results The maximum breath 13C elimination was significantly lower during the phase of intake of contraceptive pills than during withdrawal bleeding: 31.5 ± 2.2 %/h vs. 38.2 ± 1.9 %/h (p = 0.0045), whereas the time to reach it was similar on the two study days: 21.2 ± 1.2 min vs. 21.0 ± 1.1 min. Between the 27th and the 180th min of observation the cumulative breath 13C elimination was statistically significantly lower during intake of the pill than during withdrawal bleeding. No significant menstrual cycle phase-dependent fluctuations in the results of the 13C- methacetin breath test were observed in the control group. Conclusion COCs containing EE markedly inhibit hepatic microsomal function. This phenomenon must be taken into consideration when interpreting results of 13C-MBT.

Effect of peripherally and centrally administered calcitonin on gallbladder emptying in dogs

The effect of calcitonin on meal-stimulated gallbladder emptying (GBE) was examined after intravenous (i.v.) and intracerebroventricular (i.c.v.) administration in six mongrel dogs. The gallbladder contraction was surveyed by means of real-time ultrasonography in conscious dogs. Calcitonin given i.v. elicited an immediate and strong inhibition of postprandial GBE—the integrated 0- to 120-min gallbladder response was 118.1±8.0%·h after placebo, whereas it was 91.8±2.1%·h, 59.4±17.9%·h (P<0.001), and 14.2±20.5%·h (P<0.001) after 3.6, 18.0, and 90.0 pmol·kg−1 calcitonin, respectively. After i.c.v. administration (1.8 and 18.0 pmol·kg−1), only the higher calcitonin dose exerted a moderate inhibitory effect on postprandial GBE. The calcitonin doses required to evoke a 50% inhibition of meal-stimulated GBE were 15- to 10-fold lower after i.v. than i.c.v. application. Peripherally given calcitonin brought about a dose-dependent increase in the interdigestive gallbladder volume—the linear regression of the relative gallbladder volume versus calcitonin dose was y=11.60 [ln(dose+1)]+97.02 (r=0.864,P<0.001). Intravenous application of calcitonin did not affect caerulein-induced GBE. The results obtained imply that: (i) calcitonin exerts an inhibitory influence on meal-induced GBE and that this effect is more pronounced after i.v. than after i.c.v. administration, and (ii) peripherally given calcitonin does not inhibit caerulein-induced gallbladder contraction in the dog.

(13)CO2 breath tests in non-invasive hepatological diagnosis.

In liver diagnostics, a simple, non-invasive test with high sensitivity and specificity is permanently being sought in order to assess the degree of liver damage. In addition to liver biopsy, algorithms using blood parameters or elastometry are used in clinical practice. However, these methods do not provide information about the true liver reserve, so the liver breath test seem to be a promising diagnostic tool. The basis of this test depends on the ability of particular hepatocyte enzyme systems to metabolise a tested substance labelled with a stable carbon isotope. The kinetics of 13CO2 elimination with expiratory air then permits quantitative assessment of the functional liver reserve and the degree of organ damage. In this paper the most commonly used tests, grouped according to the main metabolic pathways, are described. The usefulness of liver breath tests in specific clinical situations, both as a diagnostic and prognostic tool, is presented.

Combined oral contraceptives affect liver mitochondrial activity

Abstract Objectives To examine liver mitochondrial function in women using combined oral contraceptives (COCs) containing ethinylestradiol. Methods A breath test after oral administration of 1 mg/kg 13C-alpha-ketoisocaproic acid (13C-KICA) and 20 mg/kg L-leucine was performed twice: (i) in 15 women on day 14, 15, 16, 17 or 18 of COC intake, and between day 1 and 5 of the withdrawal bleeding; and (ii) in 15 regularly menstruating females not taking hormonal contraceptives: during the luteal phase, between the 18th and the 22nd day of the cycle, and again between day 1 and 5 of the menstruation. Results In women on COCs the maximum 13C elimination in breath air (Dmax) was higher (26.8 ± 1.6%/h) than during withdrawal bleeding (23.5 ± 1.2%/h; p = 0.012). The time to reach the Dmax was similar on the two study days: 33.3 ± 2.4 min during the phase of pill intake vs. 37.0 ± 2.5 min during the pill-free interval. The one-hour cumulative breath 13C elimination was greater after two weeks of COC intake than during the withdrawal bleeding: 17.49 ± 1.03% vs. 15.32 ± 0.85% (p = 0.024). In the control group no menstrual cycle phase-dependent fluctuations in the results of the 13C-KICA breath test were observed. Conclusion The metabolism of 13C-alpha-ketoisocaproic acid augments during the intake of COCs containing ethinylestradiol, reflecting enhanced liver mitochondrial metabolic activity.

Pragmatically on the sense of taste – a short treatise based on culinary art

The sense of taste is essential for proper functioning of the organism. The authors describe, in an accessible way, the complex mechanisms of taste perception. The structure of particular taste receptors, variants of their activation, as well as physical and chemical factors modifying the sensation of taste, are presented. Exquisite culinary examples are given in order to facilitate the reader with the understanding of why, at the level of the cerebral cortex, a virtually infinite number of combinations of taste sensations can be perceived. The discourse is spiced up by reflections of the eminent philosopher of taste, J.A. Brillat-Savarin, who convinces us that food intake should be not only a physiological act, but also a refined pleasure.

Simultaneous assessment of gallbladder emptying in the dog by real-time ultrasonography and strain gauge

Patterns of meal-and cerulein-induced gallbladder emptying (GBE) were compared in four dogs equipped with a force transducer implanted onto the body of the gallbladder, and in four unoperated animals. GBE was examined by real-time ultrasonography in conscious dogs. In two dogs the ultrasonographic measurement of GBE was performed simultaneously with the registration of the strain exerted on the force transducer fixed on the gallbladder body. Implantation of the force transducer onto the gallbladder impaired neither postprandial nor cerulein-induced GBE. The contractile response of the gallbladder exhibited a nonlinear relationship to the gallbladder volume. The reduction of gallbladder volume to 50% of its basal value was accompanied by an increase in strain amounting to about 16% of the maximum response, whereas a pronounced augmentation of the strain was observed with gallbladder volume ranging between 30% and 10% of the basal value. On the other hand, the contractile response of the gallbladder registered by means of a force transducer was linearly related to the angle α contained between two radii passing from the gallbladder center towards the edges of the strain gauge:y=0.852α−30.97 (r=0.959,P<0.001) in the case of i.v. cerulein infusion at stepwisely increasing doses (0.7–2.2–7.4–22.2–66.5 pmol·kg−1h−1), andy=0.640α−17.40 (r=0.869,P<0.001) for a 1-h constant-rate 22.2 pmol·kg−1h−1 cerulein infusion.