The Effect of Sertraline on Hemodynamic Parameters and Nitric Oxide Production in Isolated Rat Hearts Subjected to Ischemia and Reperfusion.

PURPOSE: The aim of the study was to investigate the effect of sertraline on the rat heart during ischemia and reperfusion and to determine its effect on NO production. MATERIALS AND METHODS: The study was performed on isolated rat hearts. Hearts from three groups were perfused with sertraline at three different concentrations and subjected to global ischemia and reperfusion. Hearts from the other three groups were perfused with the same concentrations of sertraline but without the ischemia/reperfusion process. Two control groups were perfused with the Krebs-Henseleit solution only with and without ischemia/reperfusion process. Coronary flow (CF), heart rate (HR), left ventricular developed pressure (LVDP) and maximum rate of rise of left ventricular pressure (dP/dt max) were measured. Perfusate effluent was collected to determine creatine phosphokinase (CPK) and nitrate plus nitrite (NOx) levels. RESULTS: In non-ischemic groups, sertraline at the concentration of 10 µmol/L exerts a strong vasodilatory effect on CF, and after a short positive inotropic effect, it exerts a strong inotropic and chronotropic negative effect on isolated rat hearts and causes a direct damage to cardiomyocytes. At the concentration of 1 µmol/L, sertraline exerts an increasing negative inotropic effect. There were no hemodynamic differences between any of groups of hearts subjected to reperfusion. Sertraline had no effect on the nitric oxide concentration in coronary effluent neither in rat hearts subjected to ischemia/reperfusion nor in non-ischemic conditions. CONCLUSION: Sertraline at dose 10 µmol/L exerts a strong vasodilatory effect on coronary flow, and after a short positive inotropic effect, it exerts a strong negative effect on isolated rat hearts, causing a direct damage to cardiomyocytes. Sertraline had no effect on the nitric oxide concentration in coronary effluent.

The Negative Impact of Selective Activation of Retinoic Acid Receptors on Bone Metabolism and Bone Mechanical Properties in Rats.

BACKGROUND: Drug-induced osteoporosis is a significant health problem, as many drugs have deleterious effects on bone metabolism. Data from several studies concerning the influence of retinol on bone homeostasis are inconsistent. OBJECTIVES: The purpose of this study was to investigate the influence of tazarotene, a selective agonist of the retinoic acid receptor (RAR), on bone metabolism and bone mechanical properties in rats. MATERIAL AND METHODS: Sixteen male Wistar rats were assigned either to the group receiving tazarotene or to the control group. Serum biochemical markers of bone turnover (osteocalcin: OC, tartrate resistant acid phosphatase 5: TRACP5b, and osteoprotegerin: OPG) and the mechanical properties of bones were analyzed. RESULTS: The mean Young's modulus was 24% higher (p < 0.05) in the control group than in the group receiving tazarotene. The stiffness of femur bones was 25% lower (p < 0.05) in rats receiving tazarotene. Flexural yield stress was slightly (2%) decreased in the tazarotene group, but the difference was not statistically significant. In the tazarotene group significantly lower serum concentration of bone turnover markers were obeserved (TRACP5b: 0.86 ± 0.30 ng/mL vs. 2.17 ± 0.67 ng/mL, OC: 7.77 ± 2.28 ng/mL vs. 13.04 ± 3.54 ng/mL and OPG: 0.09 ± 0.04 ng/mL vs. 0.27 ± 0.10) than in the control group. CONCLUSIONS: Tazarotene worsened bone mechanical properties and inhibited bone turnover in rats. These results suggest that tazarotene has a negative impact on bone metabolism and that it exerts osteoporotic activity.

Effect of aging process on liver function in extracorporeal rat liver perfusion.

BACKGROUND/AIMS: Liver function appears to be well maintained in old age. However, the current state of knowledge about liver aging processes is incomplete. In this study, using extracorporeal liver perfusion model, we evaluated the differences between liver function in young and old rats. METHODOLOGY: Livers were harvested from groups of young (2 months) and old (12 months) rats and perfused for 2 hours with a perfusion fluid. After 10, 30, 60, 90 and 120 minutes of perfusion, glucose concentration as well as enzyme levels (alanine aminotransferase, aspartate aminotransferase and lactic dehydrogenase) were measured. On completion of perfusion all bile produced was collected. RESULTS: All measured parameters changed significantly as a function of perfusion time in both groups. Changes in enzyme levels were most evident between 90 and 120 minutes of perfusion. In contrast to old rats, where glucose concentration decreased during all time periods of perfusion, in young rats the glucose concentration increased at the beginning of perfusion. CONCLUSIONS: The results suggest that livers obtained from older rats are damaged to a greater extent and are more susceptible to unfavorable conditions during perfusion than livers obtained from younger rats. Also, single measurement of liver enzymes is not enough for complete liver function assessment.

[Phenotypes of oxidation and acetylation in Alzheimer's disease--preliminary report]. / Fenotyp oksydacji i fenotyp acetylacji w chorobie Alzheimera--doniesienie wstepne.

AIM: The relationship between genetically determined polymorphic oxidation and acetylation and susceptibility to some disease has aroused much interest. The aim of our study was to evaluate whether patients with Alzheimer's disease differ from healthy persons in their ability to oxidize sparteine and acetylate sulphadimidine as model substance. METHOD: Oxidation and acetylation phenotype were estimated in 20 patients with Alzheimer's disease. The control group consisted of 160 healthy volunteers for comparison of oxidation phenotype and 45 healthy subjects for comparison of acetylation phenotype. RESULTS: The phenotyping of oxidation revealed two distinct populations among 20 patients with Alzheimer's disease: 19 persons (95%) were extensive metabolizers (EMs) of sparteine and 1 person (5%) was a poor metabolizer (PMs). In 160 healthy persons, 146 persons (91.2%) were extensive metabolizers of sparteine and 14 persons (8.8%) were poor metabolizers. The difference between the frequency distribution of PMs and EMs in healthy persons and in patients with Alzheimer's disease was not statistically significant. The phenotyping of acetylation showed that among 20 patients with Alzheimer's disease 10 persons (50%) were rapid acetylators and 10 persons (50%) were slow acetylators. In 45 healthy subjects the phenotype of rapid acetylation was observed in 23 persons (5 1%) and slow acetylation in 22 persons (49%). Our study showed a lack of statistically significant differences between the percentage of rapid acetylators (51%) and of slow acetylators (49%) in the control group of healthy volunteers and in the group ofAlzheimer's disease. CONCLUSION: The results of our study may suggest that phenotypes of oxidation and acetylation are not associated with risk of the development of Alzheimer's disease.

Isolated heart perfusion according to Langendorff---still viable in the new millennium.

The isolated perfused mammalian heart preparation was established in 1897 by Oscar Langendorff. The method was developed on the basis of the isolated perfused frog heart established by Elias Cyon at the Carl Ludwig Institute of Physiology in Leipzig, Germany in 1866. Observations made using both methods at the end of the 19th and at the beginning of the 20th century led to important discoveries, forming the basis for our understanding of heart physiology. This included the role of temperature, oxygen and calcium ions for heart contractile function, the origin of cardiac electrical activity in the atrium, the negative chronotropic effect of vagus stimulation and the chemical transmission of impulses in the vagus nerve by acetylcholine. Langendorff himself demonstrated that the heart receives its nutrients and oxygen from blood via the coronary arteries and that cardiac mechanical function is reflected by changes in the coronary circulation. The method underwent many modifications but its general principle remains the same today. Blood, or more commonly crystalloid perfusates, are delivered into the heart through a cannula inserted in the ascending aorta, either at constant pressure or constant flow. Retrograde flow in the aorta closes the leaflets of the aortic valve and as a consequence, the entire perfusate enters the coronary arteries via the ostia at the aortic root. After passing through the coronary circulation the perfusate drains into the right atrium via the coronary sinus. The simplicity of the isolated mammalian heart preparation, the broad spectrum of measurements which can be done using this method, its high reproducibility and relatively low cost make it a very useful tool in modern cardiovascular and pharmacological research, in spite of a few shortcomings. In the last decade the method has brought many important advances in many areas including ischemia-reperfusion injury, cell-based therapy and donor heart preservation for transplant.

[Disorder of liver functions in a schizophrenic patient after long-term risperidone treatment--case report]. / Zaburzenia funkcji watroby w przebiegu dlugotrwalego leczenia risperidonem u chorego na schizofrenie--opis przypadku.

We present a 51-year old man with an 18-year history of chronic paranoid schizophrenia. The last four years he was treated only with risperidone at a dose of 3 mg per day. He was admitted to hospital due to a psychotic decompensation. Jaundice and skin pruritus were also observed at admission. Laboratory tests revealed elevated liver enzymes. Cholestatic and viral hepatitis were excluded. Risperidone was changed to other antipsychotic drugs. After 7 weeks of treatment the patient was discharged with significant improvement of his mental condition. The liver function test results returned to normal values except for the slightly increased total bilirubin level. Regular liver monitoring was suggested. In this case liver dysfunction was possibly correlated with long-term risperidone therapy.