The state of DNA methylation in the promoter and exon 1 regions of the human gene for the interleukin-2 receptor {alpha} chain (IL-2R{alpha}) in various cell types

The gene for the human interleukin-2 receptor     

The angiotensin II type 1-receptor blocker candesartan increases cerebral blood flow, reduces infarct size, and improves neurologic outcome after transient cerebral ischemia in rats.

The goal of the present study was to test the impact of administration time of the angiotensin II type 1-receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm3) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 +/- 8), infarct size in candesartan-treated groups was smaller (59 +/- 5, 68 +/- 10, 28 +/- 3, and 15 +/- 3, respectively; P<0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 +/- 0.18, 1.80 +/- 0.13), other treatment regimens resulted in improved neuroscores (1.33 +/- 0.16, 1.11 +/- 0.11, 0.73 +/- 0.15; P<0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 +/- 0.09 mL x g(-1) x min(-1) and 44% +/- 7% of baseline compared with 0.49 +/- 0.06 mL x g(-1) x min(-1) and 37% +/- 6%, microspheres and laser-Doppler flowmetry; P<0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.     

A new Apa LI restriction fragment length polymorphism in the low density lipoprotein receptor gene

The existence of a new Apa LI restriction fragment length polymorphism in the third intron of the low density lipoprotein (LDL) receptor gene was described. As a gene probe we used a newly constructed derivative of pLDLR 3 which did not contain the highly repetitive Alu-sequences in exon 18. This new gene probe detected all exon sequences containing restriction fragments, and enabled us to demonstrate all described polymorphisms, which might be useful for genetic linkage studies. Based on analysis of 72 unrelated normo- and hypercholesterolaemic persons, the frequency of the allele A2, which showed the additional cutting site, was determined to be 0.05. With the simplified gene probe, pLDLR delta, we also studied other polymorphisms. A clear linkage disequilibrium between the Pvu II and Msp I polymorphisms was detected. This, and the previously described linkage disequilibrium of the two Msp I polymorphisms, demonstrate that the LDL receptor gene is apparently less heterogeneous than expected from the number of described polymorphisms.     

New Conversions and Functionalization Possibilities in Pyrimido[4,5-e][1,2,4]triazine-6,8-diones

Pharmaceutical Chemistry Journal -     

Normal synthesis and expression of endothelial IIb/IIIa in Glanzmann's thrombasthenia

Glanzmann's thrombasthenia is a bleeding disorder, inherited in an autosomal recessive way and characterized by an absence or deficiency of the platelet glycoprotein (GP) IIb/IIIa complex. Recently, we and others demonstrated that cultured human umbilical vein endothelial cells synthesized a membrane protein complex similar to the platelet GP IIb/IIIa complex. In this article, we demonstrate that endothelial cells isolated from the umbilical vein of a newborn with Glanzmann's thrombasthenia, as compared with normal endothelial cells, show no difference in their ability to synthesize and express this GP IIb/IIIa complex. Our results indicate that Glanzmann's thrombasthenia is not accompanied by an "endotheliopathy."     

Neuroendocrine Changes in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage

Background

Neuroendocrine changes have been reported after ischemic stroke, subarachnoid hemorrhage, and brain trauma. As there are no corresponding data in patients with intracerebral hemorrhage (ICH) we analyzed various neuroendocrine parameters to investigate possible alterations in hormone profiles of patients with ICH.

Methods

Twenty patients with ICH were prospectively enrolled in the study. Patients were a priori parted into two groups: Ten non-ventilated patients treated on the stroke-unit (hemorrhage volumes <20 ml, “small ICH”), and 10 ventilated patients treated on the neurocritical care unit (hematoma volumes >20 ml with possible additional ventricular involvement (“large ICH”). Neuroendocrine parameters were compared between both groups referring to reference values. The following parameters were obtained over a period of 9 days in 20 patients with spontaneous supratentorial ICH: thyrotropin, free thiiodothyronine and thyroxine, human growth hormone, insulin-like growth factor 1, luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, adrenocorticotropic hormone, and cortisol.

Results

Small ICH patients were in a median 71 (54–88) years old and had a mean ICH volume of 9.5 ± 6.5 ml, whereas large ICH patients were 65 (47–80) years old and showed a mean volume of 56 ± 30.2 ml. None of the patients revealed pathological alterations for thyrotropin, free thiiodothyronine, thyroxine, human growth hormone, insulin-like growth factor 1, and testosterone. There was only a mild decrease of adrenocorticotropic hormone and cortisol on day 3 in large ICH patients. Small ICH patients showed pathologically elevated levels of luteinizing and follicle-stimulating hormone throughout the observation period. Large ICH patients showed a marked increase of prolactin that developed during the course.

Conclusions

Overall, neuroendocrine changes in ICH patients are not as profound as reported for ischemic stroke or subarachnoid hemorrhage. The clinical significance of increased LH and FSH levels in small ICH is unclear, whereas elevation of prolactin in large ICH was anticipated. Future randomized controlled trials should also focus on neuroendocrine parameters to clarify the impact of possible hormonal alterations on functional outcome.