Primary aldosteronism (PA) is associated with objectively measured lower physical fitness and blunted response of the renin-angiotensin-aldosterone system to exercise. The purpose of this pilot study was to objectively measure exercise response of the renin-angiotensin-aldosterone system and cardiopulmonary fitness changes after laparoscopic adrenalectomy (ADE) in patients with unilateral PA. We examined a total of 14 patients with confirmed PA before and after ADE, by means of spiroergometry and hormonal evaluation. As expected, after adrenalectomy basal aldosterone (Aldo) levels before exercise decreased significantly, with a concomitant increase in plasma renin (PR). The increase in Aldo (285.9±171.3 to 434.1± 278.2 ng/l; p=0.02) and blunted increase in PR (7.1±0.4 to 8.9±10.4 pg/ml; NS) post-exercise before ADE became significant after ADE Aldo post-ADE (46.8±18.8 to 106.5± 68.1 ng/l; p<0.0001) and PR post-ADE (20.1±14.5 to 33.9± 30.7 pg/ml; p=0.014). After adrenalectomy, the patients had a non-significant increase in peak workload and VO2peak. We found normalization of the renin-angiotensin-aldosterone system response to exercise with little changes in cardiopulmonary fitness six months after ADE., V. Tuka, M. Matoulek, J. Rosa, O. Petrák, O. Mikeš, Z. Krátká, B. Štrauch, R. Holaj, T. Zelinka, J. Widimský., and Seznam literatury
The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate addiction and drug withdrawal may affect circad ian rhythmicity of various hormones or the sleep/activity pattern of many experimental subjects; however, limited research has been done on the long -term effects of sustained opiate administration on the intrinsic rhythmicity in the suprachiasmatic nucleus and pineal gland. Here we compared the effects of repeated daily treatment of rats with morphine or methadone and subsequent naloxone-precipitated withdrawal on the expression of the Per1, Per2, and Avp mRNAs in the suprachiasmatic nucleus and on arylalky lamine N-acetyltransferase activity in the pineal gland. We revealed that 10-day administration and withdrawal of both these drugs failed to affect clock genes and Avp expression in the SCN. Our results indicate that opioid-induced changes in behavioral a nd physiological rhythms originate in brain structures downstream of the suprachiasmatic nucleus regulatory output pathway. Furthermore, we observed that acute withdrawal from methadone markedly extended the period of high night AA -NAT activity in the pine al gland. This suggests that withdrawal from methadone, a widely used drug for the treatment of opioid dependence, may have stronger impact on melatonin synthesis than withdrawal from morphine., D. Pačesová, J. Novotný, Z. Bendová., and Obsahuje bibliografii
The treatment of hypercholesterolemia with bile acid (BA)
sequestrants results in upregulation of BA synthesis through the
classical pathway initiated by cholesterol 7α-hydroxylase (CYP7A1). To characterize the detailed dynamics of serum lipid and BA concentrations and the BA synthesis rate in response to treatment with BA sequestrants and to determine whether the -203A/C promoter polymorphism of the CYP7A1 encoding gene (CYP7A1) affects such a response, this pilot study was carried out in healthy men (8
h omozygous for the -203A allele and 8 homozygous for the -203C allele of CYP7A1). The subjects were treated for 28 days with colesevelam
and blood was drawn for analysis before and on days 1, 3, 7, 14 and 28 of treatment. The response of lipids, BA, fibroblast growth factor-19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) to colesevelam did not differ between carriers of -203A and -203C alleles; their data were then aggregated for further analysis. Colesevelam treatment caused immediate suppression of FGF19 concentration and a fivefold increase in CYP7A1 activity, as assessed from C4 concentration, followed by a 17% decrease in LDL-cholesterol. Although total plasma BA concentrations were not affected, the ratio of cholic acid/total BA rose from 0.25±0.10 to 0.44±0.16 during treatment at the expense of decreases in chenodeoxycholic and deoxycholic acid.
Methylphenidate hydrochloride (MPH/Ritalin) is a stimulant used for off-label management of cancer-related fatigue and sedation; however, its use in pain treatment is still relatively rare. This study 1) compares the antinociceptive effect of MPH and its combination with morphine (MOR) in adult male Wistar rats after a single administration of MPH, MOR or their combination, and 2) compares the analgesic effects of opioids and Ritalin co
mbined therapy with opioid monotherapy in patients with cancer pain. To
objectively assess physical activity during a three-week monitoring period, patients were equipped with Actiwatch Score Actigraph. Patients performed daily evaluations of pain intensity and frequency, and the extent to which pain interfered with their daily life. Our research with rats supports the evidence that MPH in lower doses has the ability to enhance the analgesic properties of morphine when the two drugs are used in combination. Results from the patient arm of our study found that short
-term treatment had no significant effect on intensity or frequency of
pain, however it decreased the overall burden of pain; the combined treatment of opioid and Ritalin also showed anti-sedation effects and resulted in mild improvement in one of our patient’s quality of life.
Heartbeat reversal patterns have been monitored in the body of diapausing pupae of M. sexta 2 h before and 3 h after the injections of [Arg7]-corazonin, using noninvasive thermographic and optocardiographic methods. Large dosages (10-6 M final concentrations of corazonin in the body) caused almost immediate, adrenaline-like enhancement of the anterograde heartbeat. During the relatively short, acute phase of the tachycardia induced by corazonin, the systolic anterograde contractions of the heart increased in average from 10.5 to 24 pulses per min, culminating at 2.5 min after the injections. Duration of the acute period of tachycardia was only 7 to 20 min, which was followed by a period of slightly elevated, residual anterograde heartbeat which persisted occasionally for 1 to 3 h. Smaller dosages of corazonin (10-7M concentrations in the body) occasionally also produced a less intensive cardiotropic effect, while the more diluted samples were completely inactive. In pupae of the beetle T. molitor, injections of corazonin (10-6 M in the body) had no effect on the rate of in vivo heartbeat at all. Pharmacological analysis of the effects of corazonin in M. sexta indicated that the cardiostimulating effects of corazonin did not conform with the expected action of a peptidic neurohormone. A possibility that these effects might be artifacts produced by the low molecular breakdown products of corazonin has been discussed.
The aim of our work was to compare the effect of D-galactosamine (GalN) on primary cultures of lean and steatotic rat hepatocytes isolated from intact and fatty liver, respectively. GalN caused more severe injury to steatotic hepatocytes than to lean cells as documented by lactate dehydrogenase leakage. Necrotic mode of cell death strongly prevails over apoptosis since we did not observe any significant increase in activities of caspase 3, 8 and 9 in any group of hepatocytes treated with GalN. Reactive oxygen species (ROS) formation and lipid peroxidation were elevated in a dose-dependent manner by GalN and were significantly more pronounced in fatty hepatocytes. A decrease in the percentage of hepatocytes with energized mitochondria was observed from 30 mM and 10 mM GalN in lean and steatotic hepatocytes, respectively. Our results undoubtedly indicate that steatotic hepatocytes exert higher sensitivity to the toxic effect of GalN. This sensitivity may be caused by more intensive GalN-induced ROS production and lipid peroxidation and by higher susceptibility of mitochondria to loss of mitochondrial membrane potential in steatotic hepatocytes. In our experimental arrangement, apoptosis does not seem to participate considerably on hepatotoxic action of GalN in either group of hepatocytes., O. Kučera, H. Lotková, O. Sobotka Z. Červinková., and Obsahuje bibliografii
We studied the effect of flooding on a carabid community inhabiting grassland in a large river valley (W Poland). We used pitfall-traps to catch beetles from April to November 1999–2001. Some of the samples collected were preceded by floods during the collecting period, which enabled us to evaluate the effects of flooding on species composition and abundance. We collected 17,722 individuals belonging to 108 species. The number of species and individuals per sample differed between plots and showed a nonlinear decrease over time, from spring to autumn. Carabids were more abundant in samples collected after floods than in the control samples. In contrast, the expected cumulative number of species as a function of the number of individuals collected was lower in samples collected after floods than in the control samples. In the case of the most abundant species the species-specific responses in terms of the numbers caught after flooding differed, with those of (e.g. Agonum micans) increasing and those of (Amara plebeja, Epaphius secalis) decreasing. This study shows that floods filter the community with the result that some species increase in abundance but the overall species richness decreases. Therefore natural floods are important in shaping the structure of communities of epigeic carabids on floodplains., Pawel Sienkiewicz, Michal Zmihorski., and Obsahuje seznam literatury
a1_Renal transplantation is associated with a large number of risk factors that can have an influe nce on early renal graft function (ERGF). One of these factors could be the increasing number of obese kidney donors. The mechanisms of reduced ERGF in obese kidney donors are still poorly understood. To that end, w e compared ERGF in recipients with body mass index (BMI), perivascular fat and plasma inflammation markers of live kidney donors. We hypothesi zed that the BMI of donors would negatively correlate with an average increase of glomerular filtration rate (GFR ) and that it would also be associated wi th increased perivascular and plasma inflammation markers in the first seven days after transplantation. Between January 2013 and December 2014, some 58 living kidney transplantation pairs were included in the study. Donor and recipient demographic data, preoperative BMI, blood C -reactive protein (CRP) and adiponectin levels, perivascular adipose tissue (PAT) samples and recipient blood creatinine levels were analy zed. The median CRP of donors was 0.68 mg/l (max: 8.66 mg/l, min: 0.33 mg/l), the median of M1 macrophages (CD14+CD16+) in one gram of PAT was 5940 (max: 41 100, min: 248) and the median of adiponectin was 411 930 pg/ml (max: 14 217 000, min: 167 300) in plasma. We did not find any association between early renal graft function and the percentage o f M1 macrophages in donor perirenal adipose tissue (p=0.83, r=0.03, n=58), adiponectin (p=0.65, r=0.06, n=58) or CRP (p=0.16, r=0.2, n=58) in plasma. The obesity level of donors, expressed as BMI, did not correlate with early renal graft function in the first seven days after transplantation. The associations between ERGF and plasma and perivascular fat inflammation markers were not significant., a2_We confirmed a negative correlation between the BMI of recipients and an average increase of GFR in the first sev en days after transplantation (p<0.02, r= -0.325, N=58). We confirmed a negative correlation of adiponectin plasma concentration to the BMI of donors., F. Thieme, L. Janousek, J. Fronek, A. Kralova, S. Cejkova, I. Kralova Lesna, R. Poledne., and Obsahuje bibliografii