The peri‐microvascular edema in hippocampal CA1 area in a rat model of sepsis

Encephalopathy is a common complication of sepsis. However, little is known about the morphological changes that occur in the brain during sepsis. In this study, fecal peritonitis was induced in Wistar rats, which had been monitored for 4 h before their brains were removed and samples from the CA1 area taken. In addition to higher blood pressure with a decreasing pattern and a significant drop in rectal temperature, an increased heart rate and marked respiratory failure were observed. The tissue was investigated and compared with corresponding hippocampal samples taken from sham‐operated and not operated control groups. Significantly more peri‐microvascular edema was found in the hippocampal CA1 area in the septic group. The percentages of the peri‐microvascular edema were 158.57 ± 3.6%, 122.84 ± 1.5% and 120.24 ± 1.9% in the fecal peritonitis group, sham‐operated and not operated control groups, respectively. The results may suggest that the edema observed around the microvessels may participate in the pathogenesis of the septic encephalopathy probably by causing in the microvascular permeability characteristics.     

Response of Orbital and Central Nervous System Metastases of Retinoblastoma Following Treatment with Cyclophosphamide/Doxorubicin

A 3.5-year-old boy with orbital and central nervous system extension of unilateral retinoblastoma received chemotherapy consisting of intravenous cyclophosphamide and doxorubicin and intrathecal methotrexate. Complete shrinkage of orbital tumor, phthisis bulbi,'and disappearance of intracranial metastases occurred following chemotherapy. Response of the intra-cranial tumors reflected the combined effects of cyclophosphamide and doxorubicin; the contribution of each agent could not be assessed. Cerebrospinal fluid tumor cells persisted prior to delivery of craniospinal irradiation, and were detected again 6 weeks after completion of irradiation.     

Rapid characterization of mutagenic aromatic amines in energy-related materials by short column liquid chromatography with electrochemical detection

A liquid Chromatograph equipped with a short (3 cm) reverse phase column and electrochemical detector was used to characterize aromatic amines in shale oil, synthetic oil, and coal gasification streams. Five major peaks were produced from each sample mixture. The composition of the peaks was determined by high performance liquid chromatography with a long (25 cm) reverse phase column and by gas chromatography/mass spectrometry. Amines in the various peaks included aminonaphthalenes, aminobiphenyls, aminofluorenes, and aminophenanthrenes plus aminoanthracenes. The concentration of aminofluorenes, and aminophenanthrenes plus aminoanthracenes correlated with relative mutagenicity of the base fraction from the oils or tars. The levels of 2- and 3-ringed aromatic amines from shale oil and oil from the Great Plains commercial coal gasification plan were 24 and 184 g/g tar, respectively, while the respective mutagenicities were 8 and 214 revertants/g base fraction. This technique has the advantages of high sensitivity and rapid analysis, and could be used to screen for the presence of mutagens in synthetic fuel samples.     

Effect of dipyridamole on fluorodeoxyuridine cytotoxicity in vitro and in cancer patients

Summary Dipyridamole (DP) has previously been studied both in vitro and in vivo in combination with various antimetabolites, including methotrexate and 5-fluorouracil (5FU). We evaluated in vitro and clinically the effects of adding DP to fluorodeoxyuridine (FUDR) in colorectal cancer. Using a human colony-forming assay, we observed that 0.05 M DP increased the cytotoxicity of FUDR by a median of 33.5-fold vs 1.5-fold for 5FU against human colon-cancer cell lines. The mechanism of the DP-enhanced antitumor activity of FUDR is not completely understood but appears to be related to a profound inhibition by DP of thymidine accumulation in and FUDR efflux from colon-cancer cell lines. On the basis of these in vitro results, 28 patients with metastatic colon cancer were entered in a clinical trial of monthly courses of 0.1 mg/kg FUDR daily for 14 days and 75 mg oral DP 5 times daily for 14 days starting on the 3rd day of continuous i.v. FUDR infusion. The pharmacokinetics of DP was studied in three patients; the results showed that 98% of total serum DP was protein-bound and that free DP levels were significantly lower than the concentrations necessary for the expected in vitro DP/FUDR modulation. Treatment was well tolerated, with only 12 patients developing mild to moderate toxicity. Of 27 evaluable patients, 4 achieved a partial response that lasted 2, 3, 5, and 6+ months. This relatively low response rate (15%), which is similar to that achieved with FUDR alone, may be explained by the low steady-state plasma concentrations of free DP achieved in our patients. Other means of DP administration, such as i.v., i.a., and i.p. injection, may be required to achieve free DP concentrations necessary for successful biochemical modulation of FUDR in patients.Supported in part by grants CA17094, CA23074, and CA39629 from the National Institutes of Health, Bethesda, Md 20205, and a grant from the Arizona Chronic Disease Commission. HSG is a recipient of an American Cancer Society Career Development Award     

Enhanced cerebrovascular permeability by Metrazol: significance for brain metastases

Metrazol enhanced the penetration of two proteins (¹²⁵I human serum albumin and horseradish peroxidase), and the anticancer agent, razoxane, into the central nervous system of anaesthetized rats. Penetration was increased throughout the whole brain. With the exception of the bladder, no peripheral tissue was affected. The increase in brain permeability was temporary and reversed within 4 hours; brain levels of drug and protein were increased by up to three times.[/p]