The environmental estrogen bisphenol a inhibits estradiol-induced hippocampal synaptogenesis

Bisphenol A (BPA) is an estrogenic chemical that is widely used in the manufacture of plastics and epoxy resins. Because BPA leaches out of plastic food and drink containers, as well as the BPA-containing plastics used in dental prostheses and sealants, considerable potential exists for human exposure to this compound. In this article we show that treatment of ovariectomized rats with BPA dose-dependently inhibits the estrogen-induced formation of dendritic spine synapses on pyramidal neurons in the CA1 area of the hippocampus. Significant inhibitory effects of BPA were observed at a dose of only 40 microg/kg, below the current U.S. Environmental Protection Agency reference daily limit for human exposure. Because synaptic remodeling has been postulated to contribute to the rapid effects of estrogen on hippocampus-dependent memory, these data suggest that environmental BPA exposure may interfere with the development and expression of normal sex differences in cognitive function, via inhibition of estrogen-dependent hippocampal synapse formation. It may also exacerbate the impairment of hippocampal function observed during normal aging, as endogenous estrogen production declines.     

Determinant role of education in the ethical aspects of resuscitation: a German/Hungarian comparison

Introduction, objectives: Bioethical principles concerning Do Not Attempt Resuscitation (DNAR) orders are connected significantly with education according to our previous investigation. In order to confirm the hypothesis, Hungarian results were compared with the data gained from a highly qualified homogeneous group of German doctors, showing similar cultural traditions. Methods: The questionnaire investigated the factors influencing DNAR orders as functions of intensive medical experience, ideological view and professional education, using a 5-point visual analogue scale. Answers were assigned to categories of autonomy, futility, obtainable quality of life, resource utilization and a category of other factors detailed later. Results: The DNAR decision and termination of resuscitation are to almost the same extent determined by futility (3.29+-0.75; 3.49+-0.71) and obtainable quality of life (3.13+-1.31; 3.47+-1.34). The opinion of head of department was also important (3.24+-1.35; 3.23+-1.36). Patient's autonomy played an important role (3.15+-0.85; 2.36+-1.48) in decision making. In comparison with the Hungarian results, the only significant difference was found in the field of patient's autonomy in both not starting (p<0.0002) and terminating resuscitation (p<0.02) in favour of German doctors respecting it. Discussion: The results support the original hypothesis that consideration of modern bioethical principles, and especially the patient's autonomy are related to the level of the doctor's education. Comparing to Hungarian data there is only a minimal difference in other bioethical points, while the population of German doctors interviewed appreciated the patient's autonomy significantly higher. There should be greater discussion of ethical considerations in cardiopulmonary resuscitation education.     

Simultaneous bilateral percutaneous nephrolithotomy in children

In the paediatric section, two papers relating to the upper urinary tract are presented. The first, from Hungary, describes simultaneous bilateral percutaneous nephrolithotomy in 13 patients, where it was deemed feasible; this is the first such report. Authors from London report on unilateral nephrectomy in patients with nephrogenic hypertension, and found that it was successful in normalising blood pressure in patients with renal hypertension with a normal contralateral kidney. OBJECTIVE: To evaluate the efficacy of removing bilateral kidney stones simultaneously from children, in one session. PATIENTS AND METHODS: Thirteen patients (three girls and 10 boys, 26 kidneys; mean age 8 years, range 3-14) underwent simultaneous bilateral percutaneous nephrolithotomy (PCNL) in the same session, under general anaesthesia, starting with ureteric catheter insertion into both kidneys and using a 26 F adult nephroscope. The mean (range) stone diameter was 2 (1-3.5) cm. Three patients had staghorn stones in one of their kidneys. Ultrasonic disintegration was used; two patients had bilateral and two others unilateral endopylotomy, and one patient had percutaneous suprapubic cystolithotomy in the same session. The mean (range) operative duration was 65 (55-90) min. RESULTS: All patients were rendered stone-free; there was no severe bleeding or any other complication. On one side in one of the patients, a second session was needed because of residual stone. The nephrostomy tubes were removed 3 and 4 days after PCNL and the hospital stay was 6 (1-11) days. CONCLUSION: The advantages of simultaneous bilateral PCNL are reduced psychological stress, one cystoscopy and anaesthesia, less medication and a shorter hospital stay and convalescence, with considerable savings in cost. In experienced hands this method can be used not only in adults but also in children. To our knowledge this is the only report of this technique in children.     

Poly(adenosine diphosphate ribose) polymerase inhibition modulates spinal cord dysfunction after thoracoabdominal aortic ischemia-reperfusion

OBJECTIVE: Spinal cord injury (SCI) remains a source of morbidity after thoracoabdominal aortic reconstruction. These studies were designed to determine whether PJ34, a novel ultrapotent inhibitor of the nuclear enzyme poly(adenosine diphosphate ribose) polymerase (PARP) could modulate neurologic injury after thoracic aortic ischemia reperfusion (TAR) in a murine model of SCI. METHODS: Forty-one anesthetized male mice were subject to thoracic aortic occlusion (11 minutes) through a cervical mediastinotomy followed by 48 hours of reperfusion (TAR) under normothermic conditions. PJ34-treated mice (PJ, n = 12) were given 10 mg/kg PJ34 intraperitoneally 1 hour before ischemia and 1 hour after unclamping. The control group (UN, n = 21) received normal saline intraperitoneally 1 hour before ischemia and 1 hour after unclamping. Sham animals (n = 10) were subject to thoracic aortic exposure with no aortic clamping and similar intraperitoneal normal saline injections. PARP-1-/- (KO, n = 8) mice were subjected to the same conditions as the UN mice. Blinded observers rated murine neurologic status after TAR by using an established rodent paralysis scoring system. Murine spinal cords were subjected to cytokine (GRO-1) protein analysis as a marker of inflammation and immunohistochemical analysis (hematoxylin-eosin and PAR staining). Paralysis scores (PS) and GRO-1 levels were compared with analysis of variance, and survival data were compared with chi 2 . RESULTS: Immediately after TAR, UN and PJ mice had severe neurologic dysfunction (PS = 5.8 +/- 0.1 and 4.6 +/- 0.6, respectively; P > .05), which was significantly worse than the KO mice (PS = 1.0 +/- 0.7, P < .001). After 6, 24, and 48 hours KO mice had no discernable neurologic injury (PS = 0). Six hours after TAR, PJ mice significantly improved (PS = 1.1 +/- 0.73, P < .001) and remained improved at 24 (PS = 0.7 +/- 0.6) and 48 hours (PS = 0.6 +/- 0.6). UN mice did not improve their PS, and Sham mice showed no neurologic abnormality at any time during these experiments. The mortality at 48 hours was 0% for PJ and KO mice, 43% for UN (P = .012), and 0% for Sham. GRO-1 levels were significantly decreased in PJ and KO versus UN mice (UN, 583 +/- 119 vs PJ, 5.8 +/- 0 vs KO, 5.3 +/- 1.4 mg/pg; P < .0001). Immunohistochemistry showed evidence of decreased PAR staining and ventral motor neuron injury in PJ mice. CONCLUSIONS: Genetic deletion of PARP or inhibition of its activity (PJ34) rescued neurologic function in mice subjected to TAR. PARP inhibition might represent a novel therapeutic approach for prevention of SCI after TAR.     

Benign cystic mesothelioma, a rare tumor of the peritoneum

We report the case of a 28-year-old woman, who presented with acute abdominal and pelvic pain, the appearance of appendicitis. Because of her symptoms urgent operation was performed. Appendicetomy was performed, during the operation multiple cystic lesions were discovered on the right ovary and the peritoneal surface of the mesentery. Laparatomy was performed with removal of the visible cystic lesions, which contained mucous fluid. Final histology revealed benign cystic mesothelioma, which is a rare lesion of the peritoneum, occurring mainly in women in reproductive age. The etiology of cystic mesothelioma is still unclear. The short-term prognosis is favourable, but high recurrence rate. Some authors reported effective intraperitoneal chemotherapy, but no clinical study is available about long term outcome. We hope that surgical eradication was effective to prevent recurrence. One year after the operation the patient is complaint and symptom free.     

Aldose reductase inhibition counteracts oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation in tissue sites for diabetes complications

This study evaluated the effects of aldose reductase inhibition on diabetes-induced oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation. In animal experiments, control and streptozotocin-induced diabetic rats were treated with or without the aldose reductase inhibitor (ARI) fidarestat (16 mg . kg(-1) . day(-1)) for 6 weeks starting from induction of diabetes. Sorbitol pathway intermediate, but not glucose, accumulation in sciatic nerve and retina was completely prevented in diabetic rats treated with fidarestat. Sciatic motor nerve conduction velocity, hindlimb digital sensory nerve conduction velocity, and sciatic nerve concentrations of two major nonenzymatic antioxidants, glutathione and ascorbate, were reduced in diabetic versus control rats, and these changes were prevented in diabetic rats treated with fidarestat. Fidarestat prevented the diabetes-induced increase in nitrotyrosine (a marker of peroxynitrite-induced injury) and poly(ADP-ribose) immunoreactivities in sciatic nerve and retina. Fidarestat counteracted increased superoxide formation in aorta and epineurial vessels and in in vitro studies using hyperglycemia-exposed endothelial cells, and the DCF test/flow cytometry confirmed the endothelial origin of this phenomenon. Fidarestat did not cause direct inhibition of PARP activity in a cell-free system containing PARP and NAD(+) but did counteract high-glucose-induced PARP activation in Schwann cells. In conclusion, aldose reductase inhibition counteracts diabetes-induced nitrosative stress and PARP activation in sciatic nerve and retina. These findings reveal the new beneficial properties of fidarestat, thus further justifying the ongoing clinical trials of this specific, potent, and low-toxic ARI.     

Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells

The 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) are widely used and well tolerated cholesterol-lowering drugs. In rare cases, side effects occur in skeletal muscle, including myositis or even rhabdomyolysis. However, the molecular mechanisms are not well understood that lead to these muscle-specific side effects. Here, we show that statins cause apoptosis in differentiated human skeletal muscle cells. The prototypical representative of statins, simvastatin, triggered sustained intracellular Ca(2+) transients, leading to calpain activation. Intracellular chelation of Ca(2+) completely abrogated cell death. Moreover, ryanodine also completely prevented the simvastatin-induced calpain activation. Nevertheless, an activation of the ryanodine receptor by simvastatin could not be observed. Downstream of the calpain activation simvastatin led to a translocation of Bax to mitochondria in a caspase 8-independent manner. Consecutive activation of caspase 9 and 3 execute apoptotic cell death that was in part reversed by the coadministration of mevalonic acid. Conversely, the simvastatin-induced activation of calpain was not prevented by mevalonic acid. These data delineate the signaling cascade that leads to muscle injury caused by statins. Our observations also have implications for improving the safety of this important medication and explain to some extent why physical exercise aggravates skeletal muscle side effects.     

Thiocyanatochromium(III) complexes with pilocarpine and the analytical determination of this alkaloid (author's transl)]

Thiocyanatochromium(III) Complexes with Pilocarpine and the Analytical Determination of this Alkaloid A new reinecke salt-like compound NH₄[Cr(NCS)₄ (pilocarpine)₂] · H₂O was obtained from K₃[Cr(NCS)₆] and pilocarpine in the molten state. The constitution of the complex anion was proven by means of a series of double decomposition reactions with amines and cobalt(III)-amine bases. The structure and the thermal stability of the title compound were studied by means of UV and IR spectroscopy and derivatography. The slightly soluble compounds pilocarpine H[Cr(NCS)₄ (aniline)₂] and pilocarpine · H[Cr(NCS)₄ (morpholine)₂] were used for the oxidimetric and spectrophotometric determination of pilocarpine.