Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 1: 6-Methyl Derivatives

A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl substituent have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. While many of the compounds show activity comparable to FAA in vitro, this essentially disappears in vivo, possibly due to degradation before the compounds can reach the tumour site.     

Magnetic resonance imaging reveals no ventriculomegaly in polydrug abusers

Previous studies of cerebral structure in substance abusers yielded controversial results, largely due to issues of subject selection and/or limitations of experimental techniques. The purpose of the present study was to assess whether the ventricle-to-brain ratio (VBR), determined volumetrically by magnetic resonance imaging (MRI), differed in polysubstance abusers (n = 10), as compared with age-matched controls (n = 10). Subjects were male volunteers 21–39 years of age. The values of VBR in the polydrug abuse group were not larger than those in control group, nor was there any tendency toward relative ventriculomegaly in the substance abusers. Therefore, the present findings provide no evidence that polysubstance abuse produces abnormalities of gross brain structure in relatively young and physically healthy men.     

Excision of a Clival and Upper Cervical Pheochromocytoma by an Extended Maxillotomy Approach: A Case Report

By use of an extended maxillotomy approach, greater surgical access is provided to the midline skull base in comparison with lateral approaches. We describe this technique used to debulk a tumor extending from the sphenoid sinus across the craniocervical junction to the second cervical vertebrae.     

Detection of haematoporphyrin derivative and haematoporphyrin excited states in cell environments

The photosensitiser currently used in the photodynamic therapy of cancer is haematoporphyrin derivative. Pulsed laser studies of this material and also of the "parent" molecule haematoporphyrin in polyoma-transformed fibroblast cells have now been studied. We report, for the first time, the observation of the triplet absorption of these sensitisers in cells. The corresponding triplet-triplet spectra are red shifted compared to aqueous buffer, lambda(max) 420 nm shifts to 460 nm. We also report our failure to observe singlet oxygen from the cells even though the triplet state can be seen to interact with the oxygen and even though singlet oxygen can be readily detected with the same sensitisers bound to serum albumin.     

Should results of ultrasound Doppler studies be reported in units of frequency or velocity?

There is a current tendency to report the results of ultrasound Doppler studies in units of velocity instead of Doppler frequency. This is probably motivated by the intuitive feeling that blood flow studies should naturally be reported in cm/s and the notion that "velocity" is a normalizing factor for Doppler ultrasound studies. In order to determine velocity, the Doppler angle theta or angle formed by the ultrasound beam and flow velocity vector, must be known. It is not possible, using currently available systems, to obtain an accurate estimate of this angle. The physics related to the Doppler equation are reviewed in this paper along with examples to illustrate the origin and magnitude of errors that could arise when reporting in units of velocity. Guidelines are provided for thinking about and reporting results of Doppler studies in units of velocity. An understanding of the Doppler equation and its use in clinical studies are promoted in this paper to enhance the diagnostic usefulness of Doppler ultrasound studies and to reduce serious errors which could lead to faulty information dictating patient management.     

Chlorinated hydrocarbon levels in human serum: Effects of fasting and feeding

Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4–5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p < 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), andp,p-dichlorodiphenyldichloroethylene (p,p-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, andp,p-DDE concentrations were corrected by total serum lipids, results from fasting and nonfasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.     

The wheat variety used in the diet of laying hens influences colonization with the intestinal spirochaete Brachyspira intermedia.

This study investigated whether feeding different wheat varieties to laying hens could influence colonization with the intestinal spirochaete Brachyspira intermedia. Fifty ISA-Brown laying hens were divided into two groups. One group were fed a laying-hen diet formulated with wheat variety Westonia, and one were fed the diet incorporating variety Stilleto. Each group was divided into 15 hens experimentally infected with B. intermedia and 10 uninfected controls. The 30 infected hens were housed in individual cages in one room, and the controls were similarly housed in another room. Following administration of cultures of B. intermedia strain HB60 by crop-tube over 3 days, cloacal swabs were taken for spirochaete culture every 3 to 4 days. The water content of caecal faeces, and egg production and body weight were measured weekly. The hens were killed after 4 weeks, the caeca cultured for spirochaetes and the viscosity of the ileal contents measured. A total of 48/120 (40%) of the excreta samples from infected hens fed Westonia contained B. intermedia, compared with 21/120 (17.5%) for Stiletto (P = 0.0002). The ileal viscosity of hens fed Westonia also was higher (P = 0.048), but viscosity was not clearly related to the non-starch polysaccharide (NSP) content of the wheats. Westonia had a slightly higher total NSP content than Stiletto, but the ratio of soluble to insoluble NSP was lower. Infected hens developed wetter excreta, but neither infection nor diet altered egg production. In conclusion, the wheat variety can influence colonization with B. intermedia, apparently through diet-related alterations in the intestinal microenvironment.     

Hepatic DNA adduct dosimetry in rats fed tamoxifen: a comparison of methods

Liver homogenates from rats fed tamoxifen (TAM) in the diet were shared among four different laboratories. TAM-DNA adducts were assayed by high pressure liquid chromatography-electrospray tandem mass spectrometry (HPLC-ES-MS/MS), TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), and (32)P-postlabeling with either thin layer ((32)P-P-TLC) or liquid chromatography ((32)P-P-HPLC) separation. In the first study, rats were fed a diet containing 500 p.p.m. TAM for 2 months, and the values for measurements of the (E)-alpha-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-N(2)-TAM) adduct in replicate rat livers varied by 3.5-fold when quantified using 'in house' TAM-DNA standards, or other approaches where appropriate. In the second study, rats were fed 0, 50, 250 or 500 p.p.m. TAM for 2 months, and TAM-DNA values were quantified using both 'in house' approaches as well as a newly synthesized [N-methyl-(3)H]TAM-DNA standard that was shared among all the participating groups. In the second study, the total TAM-DNA adduct values varied by 2-fold, while values for the dG-N(2)-TAM varied by 2.5-fold. Ratios of dG-N(2)-TAM:(E)-alpha-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-N(2)-N-desmethyl-TAM) in the second study were approximately 1:1 over the range of doses examined. The study demonstrated a remarkably good agreement for TAM-DNA adduct measurements among the diverse methods employed.     

Initiation and pattern of angiogenesis in wound healing in the rat

The object of this study was to examine the initiation and pattern of capillary growth associated with wound healing. Collagen sponges were implanted subcutaneously in the hind limbs of adult male rats to stimulate the formation of granulation tissue. Blood vessels of the hind limbs of euthanized rats were perfused with Mercox (an acrylic monomer) via the abdominal aorta at selected periods of time following sponge implantation. When the perfusate was completely cured, the sponge and parajacent tissues were excised and subsequently macerated by alternating immersion in 40% KOH and distilled water. Cast replicas of the vascular lumina were coated with gold and imaged by scanning electron microscopy. At 6 hr, punctate depressions at the periphery of the replicas of vein and venule lumina were noted. The depressions represented sites of leukocyte margination. By 24 hr, the depressions increased numerically, indicating a great increase in the sites of leukocyte margination. The number of these depressions decreased by 48 hr. Concomitantly, the depressions representing endothelial cell nuclei became more pronounced, indicating nuclear hypertrophy of these cells. In addition, capillary bud formation was initiated. At 72 hr, capillary buds were quite apparent and arose solely from venules. Between 7 and 14 days, replicas of capillary lumina were longer and formed an elaborate network, presumably by end-to-end, side-to-side, and end-to-side anastomoses. The network was formed circumferential to the sponge and then capillary sprouts entered the sponge's interstitial spaces.