Synthesis and antitumor activity of 5-(5′,6′-benzocoumaro-3′-yl)methylaminouracil hydrobromide and its liposomal medicinal form

The antitumor activity of 5-(5′,6′-benzocoumaro-3′-yl)methylaminouracil (BCMU) and its liposomal medicinal form was studied in comparison to 5-fluorouracil (5-FU), a well-known antitumor drug widely used in oncological practice. The half-lethal dose of BCMU is 14.8 ± 4.2 mg/kg, while the optimum effective dose of the drug is 6 mg/kg. In this dose, BCMU combines low toxicity with significant antitumor activity, which is manifested by increased tumor growth inhibition (TGI) at a 19% increase in the lifetime (LT) of experimental animals. The antitumor activity of the liposomal form of BCMU is quantitatively and qualitatively superior to that of the nonmodified compound and 5-FU, which is manifested by the most pronounced TGI value and by a significant LT increase. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 6, pp. 6–7, June, 2006.     

Neuroimaging in Pineal Tumors

BACKGROUND AND PURPOSE: The authors report radiological findings in 11 tumors in the pineal region, which were histologically diagnosed as germinomas, pineocytomas pineoblastomas, ependymomas, teratomas, and astrocytomas. METHODS: Computed tomography (CT) was performed in seven patients and magnetic resonance imaging (MRI) was performed in all patients. RESULTS: CT showed a solid or solid/cystic mass with variable contrast enhancement. MRI showed a heterogeneous mass, with hypointense signal on T1 and iso/hyperintense signal on T2-weighted images (WI) and gadolinium enhancement. Extension to adjacent structures occurred in five patients and spread through the cerebral spinal fluid (CSF) in two. CONCLUSIONS: Pineal region tumors have no pathognomonic imaging pattern. MRI and CT are complementary in diagnosis and are important to determine localization, extension, and meningeal spread.     

Effect of cordarone on the eye (results of long-term follow-up of the treatment and prevention of arrhythmia)

Thirty-one patients who received a prolonged maintenance therapy with cordarone to treat and prevent cardiac arrhythmias underwent an ophthalmologic examination. The treatment lasted 1.5 to 51 months. The signs of keratopathy were detected in 24 (77.4%) patients using a slit lamp biomicroscopy. There is a relationship between the severity of keratopathy and a daily dose of cordarone: in most cases signs of stage I keratopathy were detectable when the daily dose was up to 200 mg. Keratopathy appears to be reversible after the drug has been discontinued.     

Moderate soft tissue trauma delays new bone formation only in the early phase of fracture healing.

The aim of this study was to investigate the effect of a moderate soft tissue trauma to the course of fracture healing in a standardized animal model. Thirty-eight Wistar rats were randomly divided into a fracture group (F, n = 19) and a group with a fracture and a soft tissue trauma (F + STT, n = 19). The fracture and the soft tissue trauma were created using an impact device with a standardized energy. All fractures were stabilized by two Kirschner wires. Three rats were measured for blood flow and sacrificed at days 1, 3, 7, and 14, and seven rats at day 28, from both groups. A three-point bending test was performed on the healed tibia after 28 days. During the first 24 h there was a reduction in blood flow, which was more pronounced in the F + STT group than in the F group. From histological sections, the shape of the callus formation, as well as the tissue distribution of newly formed bone, fibrous cartilage and fibrous connective tissue were determined. Distinctly more periosteal new bone formed and a larger callus formed at days 3 and 7 in group F compared to group F + STT. However, by days 14 and 28, the ossification and overall callus size no longer showed differences between the two groups. A fast recovery of blood flow and callus formation took place in the F + STT group, which led to similar histological and biomechanical results in fracture healing observed after 28 days between the two groups.     

Ultrasonography in the detection of cervical incompetency

In 80 pregnancies with clinical and ultrasonic signs of cervical incompetency, the length of the cervix and the thickness of the anterior wall of a lower uterine segment have been evaluated ultrasonically. We have also measured the width of the endocervical canal and studied the prolapse of fetal membranes (with fetal parts) into the endocervical canal. We evaluated these same parameters in 80 healthy pregnancies. The length of the cervix, the thickness of the anterior wall of a lower uterine segment, and the width of the endocervical canal were followed longitudinally in the patients from the 10th to the 36th gestation week. No statistically significant differences between age groups were found. In four age groups at risk for cervical incompetency, cervical lengths and wall thickness were significantly different (p less than 0.001) from those in comparable controls. Forty-five percent of the patients in the at-risk group, with cervical cerclage, delivered at 37.3 (range: 32 to 41) weeks and 6.25% of pregnancies ended in abortion when the amniotic membrane herniated into the cervical canal, with or without some part of the fetus.     

Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury. Tumor necrosis factor-alpha (TNFalpha) is protective in LPS-induced preconditioning yet exacerbates neuronal injury in ischemia. Here, we define dual roles of TNFalpha in LPS-induced ischemic tolerance in a murine model of stroke and in primary neuronal cultures in vitro, and show that the cytotoxic effects of TNFalpha are attenuated by LPS preconditioning. We show that LPS preconditioning significantly increases circulating levels of TNFalpha before middle cerebral artery occlusion in mice and show that TNFalpha is required to establish subsequent neuroprotection against ischemia, as mice lacking TNFalpha are not protected from ischemic injury by LPS preconditioning. After stroke, LPS preconditioned mice have a significant reduction in the levels of TNFalpha (approximately threefold) and the proximal TNFalpha signaling molecules, neuronal TNF-receptor 1 (TNFR1), and TNFR-associated death domain (TRADD). Soluble TNFR1 (s-TNFR1) levels were significantly increased after stroke in LPS-preconditioned mice (approximately 2.5-fold), which may neutralize the effect of TNFalpha and reduce TNFalpha-mediated injury in ischemia. Importantly, LPS-preconditioned mice show marked resistance to brain injury caused by intracerebral administration of exogenous TNFalpha after stroke. We establish an in vitro model of LPS preconditioning in primary cortical neuronal cultures and show that LPS preconditioning causes significant protection against injurious TNFalpha in the setting of ischemia. Our studies suggest that TNFalpha is a twin-edged sword in the setting of stroke: TNFalpha upregulation is needed to establish LPS-induced tolerance before ischemia, whereas suppression of TNFalpha signaling during ischemia confers neuroprotection after LPS preconditioning.