1-Thioangelicin: crystal structure, computer-aided studies and photobiological activity

1-Thioangelicin is a furocoumarin analog synthesized to investigate the role of the substitution of sulfur for oxygen in the parent compound angelicin. The compound was examined by X-ray diffraction, and its interaction with DNA, both in the dark and by UVA irradiation, studied by means of linear flow dichroism, chromatography and (1)H NMR. Further insight into the steric and electronic features of 1-thioangelicin has been reached through theoretical calculations, including molecular mechanics optimization, docking studies and frontier molecular orbital investigations. The experimental data indicate that thioangelicin is able to intercalate in the DNA helix and subsequent irradiation yields a cis-syn adduct, in agreement with theoretical calculations within the lower/higher singly occupied molecular orbital formalism. Antiproliferative activity has been assessed on Balb/c 3T3 cultured cells.     

Gender and age differences in chief complaints of acute myocardial infarction (Worcester Heart Attack Study)

We examined gender and age differences for chief symptom complaints in a population-based sample of 881 women (43%) and 1,192 men (57%) hospitalized for acute myocardial infarction (AMI). Women, in particular older women, were less likely than men to have a chief complaint of chest pain associated with AMI. Overall, a large proportion of women and men whose AMI was ultimately diagnosed did not present with chest pain as their chief complaint.     

Fetal brain injury

Improvements in MRI techniques widen the indications for fetal brain imaging and fetal brain injury represents the third indication of fetal brain magnetic resonance imaging (MRI) after the evaluation of suspected central nervous system (CNS) malformations and ventricular dilatation. Optimal MR imaging technique is necessary in order to collect as much data as possible about the fetal brain. Diffusion images can be used routinely in addition to the standard protocol of fetal brain MRI that consists of T1 and T2 weighted images of the fetal brain. Monovoxel proton magnetic resonance spectroscopy can also be performed in utero, but this technique is still more part of research protocol than of routine clinical protocol. Fetal brain injury includes hypoxia-ischemia, congenital infections (especially toxoplasmosis and cytomegalovirus infections), brain damage due to malformation such as vascular brain malformation and heart malformation, pregnancies at risk of fetal brain damage, and even inherited metabolic diseases, especially mitochondrial diseases. MRI findings in fetal brain injury consist of acute or chronic lesions that can be seen alone or in combination. Acute response of the fetal brain is less commonly seen than the chronic response compared to the brain response encountered in the postnatal period.     

Malignant hypertension and cerebral haemorrhage in Seckel syndrome

Seckel syndrome is an autosomal recessive condition with severe short stature and facial and neurological anomalies. Intracranial haemorrhage, due to rupture of a cerebral aneurysm, is a very rare complication of this syndrome. Malignant hypertension may play an important role in the aetiology of the aneurysm and early detection is essential in order to prevent organ damage. Conclusion:we report a new case of Seckel syndrome associated with malignant hypertension and cerebral haemorrhage.Abbreviations BA basilar artery - MCA middle cerebral artery - PICA posterior internal cerebral artery - PICU paediatric intensive care unit - SS Seckel syndrome     

Encapsulating sclerosing peritonitis: report of 2 cases

SEP is an increasingly seen complication of CAPD; we have the occasion to see again this condition because two patients came under our observation. We have remarked the unknown etiology and pathogenesis, the difficult diagnosis and therapy, and the often poor prognosis.     

Photosensitization of DNA strand breaks by three phenothiazine derivatives

The interaction and the photosensitizing activity of three phenothiazine derivatives, fluphenazine hydrochloride (FP), thioridazine hydrochloride (TR), and perphenazine (PP), toward DNA were studied. Evidences obtained from various spectroscopic studies such as fluorimetric and linear dichroism measurements indicate that these derivatives bind to the DNA at least in two ways: intercalation and external stacking on the DNA helix, depending on their relative concentrations. Irradiation of supercoiled plasmid DNA in the presence of these phenothiazines leads to single strand breaks. The DNA photocleavage appears to be due to externally bound molecules rather than to those intercalated. The highest photocleavage activity was observed with PP and TR whereas FP was less efficient. The efficiency of the photocleavage in aerated and deaerated solutions does not change thus indicating that an involvement of singlet oxygen can be excluded. Primer extension analysis of plasmid DNA irradiated in the presence of phenothiazines indicates that photocleavage of DNA occurs predominantly at Gua and Cyt residues. Laser flash experiments carried out in the presence of 2'-deoxyguanosine 5'-monophosphate reveal an efficient electron transfer between the nucleotide and the radical cations produced by photoionization of the phenothiazines. In the presence of DNA, an electron transfer process takes place within the laser pulse from the lowest singlet state of phenothiazines to the DNA bases; the time-resolved measurements showed that the back-electron transfer is a negligible decay pathway for the charged species.     

6-methylapigenin and hesperidin: new valeriana flavonoids with activity on the CNS

Valerian is an ancient tranquillizing drug obtained from the underground organs of several Valeriana species. Its active principles were assumed to be terpenoids in the form of valepotriates and/or as components of the essential oil. However, unknown active compounds were not discarded and synergic effects were suspected.We have recently isolated 6-methylapigenin (MA) from Valeriana wallichii and proved that it is a benzodiazepine binding site (BDZ-bs) ligand [Planta Med. 68 (2002) 934].The present paper is the first report of the presence of 2S(-)-hesperidin in valeriana and describes that it has sedative and sleep-enhancing properties. MA, in turn, was found to have anxiolytic properties and was able to potentiate the sleep-enhancing properties of hesperidin (HN).MA and HN are new members of the growing family of natural flavonoids with activity on the CNS, and their properties suggest that they are promising drug leads in the field.     

Interstitial boost and altered fractionation as novel approaches to dose escalation in the radiotherapy of glioblastoma multiforme

INTRODUCTION: The practice of image-based three dimensional treatment planning and conformal radiotherapy techniques give the opportunity to elaborate optimal treatment forms for primary brain tumours. PURPOSE: The authors examined the effect of two novel dose escalation methods on glioblastoma patients. METHODS: In nine cases they treated T1 tumours with single HDR-AL boost of 10-12 Gy dose following the conventional fractionated 60 Gy external beam radiotherapy. In fifteen patients with T2-4 tumours an intensified, hypofractionated regimen with 2.25-2.5 Gy daily and 60 Gy total dose was applied. All the treatments were carried out with image-based conformal methods. RESULTS: Majority of patients endured treatments without neurological deterioration. Transient neurotoxiticy was noticed in one and two cases, respectively. The median survival times (MST) were found to be 17 months (range: 9-25) and 12 months (range: 6-38) in the two groups, respectively. With respect to all patients, the MST was 13 months, while this value in the conventional treatment is generally considered to be 9-10 months. All the three patients who survived more than 18 months was treated with temozolamide chemotherapy as well. CONCLUSION: Based on own experience and current knowledge of authors, it seems reasonable to apply higher biological dose focal radiotherapy and chemotherapy in case of glioblastoma patients with better prognosis. To define the optimal treatment regimens randomised clinical trials should be executed.