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Patterns of fractionation for palliation of bone metastases.

The patterns of fractionation used to treat bone metastases in a single centre in two time periods were determined. Clinical audit was carried out, for two periods of 6 months each, in 1988 and 1993. Data recorded included patient, tumour and treatment variables. Palliation of bone metastases represented 40% and 44% of palliative treatment courses, and 20% and 21% of total treatment courses, respectively, in both time periods. Shorter treatment schedules were used in 1993 compared to 1988, with mean fraction numbers of 6.4 versus 8.5, respectively (P < 0.001). This reduction in fraction numbers occurred for the common primary tumour sites. In 1993, the mean numbers of fractions used were related to the primary tumour site (7.8 fractions for breast, 5.0 for lung, 6.7 for melanoma, 6.4 for other primary sites, P = 0.05), the treatment site (7.3 fractions for weight-bearing bones, 4.0 for non-weight-bearing bones, P < 0.001) and patient address (6.0 fractions for city postcode vs 7.8 for country postcode, P = 0.02). Treating radiation oncologist (5.7-7.8 mean fractions, P = 0.06) and patient age (P = 0.56) were not significant factors for the number of fractions used. It is likely that there were multiple causes for a reduction in the number of fractions used to treat bone metastases, including the results of clinical trials and increasing pressure to optimize the use of scarce resources. However, patients who may have a better prognosis (breast primary) and those with metastases in weight-bearing bones continued to receive longer treatment schedules.

Analysis of Variance↗

Isolation of mitogenic and adjuvant active fractions from various species of Nocardiae.

Delipidated lysozyme digests of Nocardia opaca, N. corallina, and N. rubra have been fractionated by Sephadex filtration. The mitogenic and adjuvant activities of the fractions thus obtained have been investigated. All fractions are mitogenic except the last fraction of N.rubra, but the N. opaca products induce a stronger stimulation of mouse spleen lymphocytes than the corresponding fractions of the two other species. The activity of the first Sephadex fractions of each strain has been compared to other mitogens (concanavalin A, lipopolysaccharide). All fractions are adjuvant, although one of them, the last Sephadex fraction of N. rubra, does not contain peptidoglycan; its activity must thus be attributed to another kind of molecule. Fractionation of the first Sephadex fraction of N. opaca by centrifugation in glacial acetic acid led to a separation of adjuvant and mitogenic activities.

Adjuvants, Immunologic↗

Protein synthesis of muscle fractions from the small intestine in alcohol fed rats.

The effects of chronic ethanol feeding on the amounts and synthesis rates of cytoplasmic, contractile, and stromal protein fractions were investigated in the small intestine of eight pairs of immature and seven pairs of mature rats. Treated rats were fed ethanol as 36% of total energy in a nutritionally adequate liquid diet. Paired controls were fed isovolumetric amounts of the same diet in which ethanol was substituted by isocaloric glucose. After six weeks the total cytoplasmic and contractile protein content in immature rats was reduced by 18% and 31%, respectively (p less than or equal to 0.007). The decline in the stromal protein content (26%) was not statistically significant (p = 0.130). In mature rats the protein contents were also reduced in the cytoplasmic (25%, p = 0.035) and contractile (27%, p = 0.005) protein fractions, though the stromal protein fraction was unaltered (p = 0.913). In immature rats fractional rates of protein synthesis in cytoplasmic and contractile protein fractions of the small intestine were unaltered by chronic ethanol feeding (p less than or equal to 0.853). In mature rats, the synthesis rates of corresponding fractions declined, by 18% and 31%, respectively, but were also not statistically significant (p less than or equal to 0.369). Absolute rates of protein synthesis in immature rats fell by 6% (p = 0.549) in the cytoplasmic and 31% in the contractile protein fraction (p = 0.045). In mature rats, the corresponding reductions were 38% (p = 0.106) and 48% (p = 0.033), respectively. Virtually no radioactivity could be detected in the stromal fraction, signifying very low synthesis rates. Chronic ethanol feeding reduces the amount of protein in the small intestine of the immature and mature rat with the contractile protein fraction showing the greatest decrease. In the absence of statistically significant reductions in fractional synthesis rates a partial adaptation in turnover rates may have occurred.

Animals↗

Doubly labeled water method: in vivo oxygen and hydrogen isotope fractionation.

The accuracy and precision of the doubly labeled water method for measuring energy expenditure are influenced by isotope fractionation during evaporative water loss and CO2 excretion. To characterize in vivo isotope fractionation, we collected and isotopically analyzed physiological fluids and gases. Breath and transcutaneous water vapor were isotopically fractionated. The degree of fractionation indicated that the former was fractionated under equilibrium control at 37 degrees C, and the latter was kinetically fractionated. Sweat and urine were unfractionated. By use of isotopic balance models, the fraction of water lost via fractionating routes was estimated from the isotopic abundances of body water, local drinking water, and dietary solids. Fractionated water loss averaged 23% (SD = 10%) of water turnover, which agreed with our previous estimates based on metabolic rate, but there was a systematic difference between the results based on O2 and hydrogen. Corrections for isotopic fractionation of water lost in breath and (nonsweat) transcutaneous loss should be made when using labeled water to measure water turnover or CO2 production.

Body Water↗

The effect of crude and purified Cerastes vipera venom protein fractions on respiratory chain function in cultured human fibroblasts.

This study was conducted to investigate the effect of crude and venom protein fractions of Cerastes vipera on the major enzymatic components of the respiratory chain in cultured human fibroblasts. Cerastes vipera crude venom was fractionated into seven protein fractions by using 8% preparative native polyacrylamide gel electro-phoresis. The effect of crude venom and purified venom fractions (F1-F7) on respiratory chain function in cultured human fibroblasts was investigated. Confluent fibroblast cultures were incubated with crude venom and venom protein fractions for a fixed period of three hours at 37 degrees C. Crude venom and venom protein fractions 2, 4, 5 and 6 significantly increased the production of lactate as compared to control fibroblasts. The production of pyruvate was markedly decreased in all these cell lines. The ratio of lactate/pyruvate was increased in the cells and in the culture medium by crude venom and venom protein fractions 2, 4, 5 and 6. On the other hand fractions 1,3 and 7 exhibited no effect in relation to lactate and pyruvate production. Similarly the crude venom protein and venom protein fractions 2, 4, 5 and 6 significantly lowered the activity of the major enzymatic component of the respiratory chain in fibroblast mitochondria. In conclusion it is apparent that the crude and venom protein fractions 2, 4, 5 and 6 resulted in a significant lowering of the mitochondrial respiratory chain activity in cultured human fibroblasts.

Animals↗

A new approach to noninvasive evaluation of aortic regurgitant fraction by two-dimensional Doppler echocardiography.

The aortic regurgitant fraction was estimated noninvasively in 20 patients with aortic regurgitation from systolic aortic and pulmonary volume flow determined by duplex Doppler echocardiography. By assuming that an excess of the aortic volume flow (AF) compared with the pulmonary volume flow (PF) is due to aortic regurgitant flow, the aortic regurgitant fraction (RF) was calculated as follows: RF(%) = (AF - PF)/AF X 100. The aortic and pulmonary volume flows were determined as products of systolic integrals of ejection flow velocities and cross-sectional areas of the left and right ventricular outflow tracts, respectively. The Doppler estimate of the regurgitant fraction was compared by semiquantitative grading (1+ to 4+) by cineaortography and with the measurement of regurgitant fraction by catheter technique. The mean Doppler-determined aortic regurgitant fraction was 2.4% for normal subjects, 28.0% for the patients with 1+, 32.6% for the patients with 2+, 53.3% for the patients with 3+, and 62.4% for the patients with 4+. A fair correlation was found between Doppler estimates of regurgitant fraction and semiquantitative cineaortographic grades (r = .80, p less than .01). In the patients without associated mitral regurgitation, a close correlation was observed between Doppler and catheter estimates of regurgitant fraction (r = .96, p less than .01; y = 1.0x - 0.08). In the patients with associated mild mitral regurgitation, however, Doppler estimates of regurgitant fraction substantially underestimated those determined by the conventional catheter technique, which cannot separately quantitate the aortic regurgitant fraction in the presence of mitral regurgitation. These observations indicate that the proposed Doppler technique provides a useful method to evaluate the aortic regurgitant fraction specifically regardless of the presence of associated mitral lesions.

Adolescent↗

Renal artery stenosis and ischemia. Effect on renal blood flow and extraction fraction.

The clearance of [131I]orthoiodohippurate and 99mTc-mercaptoacetyltriglycine provide a measure of effective renal plasma flow, yet these clearances are proportional to renal plasma flow only if the extraction fraction remains constant. To determine the effect of unilateral renal artery stenosis, captopril, renal ischemia, and partial renal vein occlusion on renal blood flow and the extraction fraction of [131I]orthoiodohippurate, 99mTc-mercaptoacetyltriglycine, and [125I]iothalamate, we conducted a series of constant infusion studies in Sprague-Dawley rats. Renal artery flow reduction of approximately 70% decreased the extraction fraction of all three agents (P < or = .05). Captopril had no effect on extraction fraction in controls, but it produced a further decrease in extraction fraction of 99mTc-mercaptoacetyltriglycine and [131I]orthoiodohippurate in rats with renal artery stenosis (P < or = .05). Ischemia resulted in a 16% decrease in flow (P < .01) but a much larger (47% to 65%) decrease in extraction fraction of all three agents (P < .002). Partial renal vein occlusion also decreased the extraction fraction of all three agents (P < or = .05). The changes in extraction fraction imply that the clearances of [131I]orthoiodohippurate and 99mTc-mercaptoacetyltriglycine in disease states may not be proportional to renal plasma flow. Furthermore, in rats with renal artery stenosis it appears that renal blood flow must fall below a critical threshold of approximately 58% before extraction fraction decreases; as renal blood flow is further reduced below this threshold, there is a corresponding reduction in extraction fraction (P < .01).

Animals↗

Single course IMRT plan to deliver 45 Gy to seminal vesicles and 81 Gy to prostate in 45 fractions.

We treat prostate and seminal vesicles (SV) to 45 Gy in 25 fractions (course 1) and boost prostate to 81 Gy in 20 more fractions (course 2) with Intensity Modulated Radiation Therapy (IMRT). This two-course IMRT with 45 fractions delivered a non-uniform dose to SV and required two plans and two QA procedures. We used Linear Quadratic (LQ) model to develop a single course IMRT plan to treat SV to a uniform dose, which has the same biological effective dose (BED) as that of 45 Gy in 25 fractions and prostate to 81 Gy, in 45 fractions. Single course IMRT plans were compared with two-course IMRT plans, retrospectively for 14 patients. With two-course IMRT, prescription to prostate and SV was 45 Gy in 25 fractions and to prostate only was 36 Gy in 20 fractions, at 1.8 Gy/fraction. With 45-fraction single course IMRT plan, prescription to prostate was 81 Gy and to SV was 52 or 56 Gy for a alpha/beta of 1 and 3, respectively. 52 Gy delivered in 45 fractions has the same BED of 72 Gy3 as that of delivering 45 Gy in 25 fractions, and is called Matched Effective Dose (MED). LQ model was used to calculate the BED and MED to SV for alpha/beta values of 1-10. Comparison between two-course and single course IMRT plans was in terms of MUs, dose-max, and dose volume constraints (DVC). DVC were: 95% PTV to be covered by at least 95% of prescription dose; and 70, 50, and 30% of bladder and rectum should not receive more than 40, 60, and 70% of 81 Gy. SV Volumes ranged from 2.9-30 cc. With two-course IMRT plans, mean dose to SV was non-uniform and varied between patients by 48% (54 to 80 Gy). With single-course IMRT plan, mean dose to SV was more uniform and varied between patients by only 9.6% (58.2 to 63.8 Gy), to deliver MED of 56 Gy for alpha/beta - 1. Single course IMRT plan MUs were slightly larger than those for two-course IMRT plans, but within the range seen for two-course plans (549-959 MUs, n=51). Dose max for single-course plans were similar to two-course plans. Doses to PTV, rectum and bladder with single course plans were as per DVC and comparable to two-course plans. Single course IMRT plan reduces IMRT planning and QA time to half.

Adenocarcinoma↗

Characterization of the human chorionic gonadotrophin fractions in pregnancy urine.

The human chorionic gonadotrophin (hCG) preparation (ca. 3000 IU/mg) from pooled pregnancy urine has been fractionated using anion-exchange and gel exclusion chromatography. The various fractions, many of which were heterogeneous, were assayed using radioimmunoassay (RIA) and a testicular radio-receptor assay (RRA). Three fractions were obtained with potencies between 9000 and 20 000 IU/mg); five fractions were characterized by potencies between 1000 and 6000 IU/mg; and four fractions exhibited low potencies (less than 500 IU/mg). A linear relationship between RRA and RIA potency (P) was found to exist for the various fractions: In(PRRA) = 1.14 In(PRIA) - 1.67. The major fractions, which exhibited various potencies, were further characterized by amino acid and carbohydrate analysis. Urine was collected from an individual at various times of gestation, and the hCG fraction was concentrated by benzoic acid and ethanol precipitation. Ion-exchange chromatography of the hCG fraction yielded multiple immunoreactive components throughout pregnancy; thus the observed heterogeneity in the commercial preparation does not appear to result from processing pooled urine from numerous donors. Also, heterogeneity was observed in an individual donor whose urine was not treated with the benzoic acid and alcohol fractionation scheme. It seems indisputable that individual urinary hCG is heterogenous, and this does not appear to reflect isolation artefacts.

Amino Acids↗

Effect of temperature on fatty acid composition in each lipid fraction of Spirometra erinaceieuropaei plerocercoids.

The effects of temperature and host fatty acids on the fatty acid contents of Spirometra erinaceieuropaei plerocercoids were investigated to clarify their role in sparganosis. After 24 hr incubation at 18 C in host snake serum, omega6 series fatty acids, especially arachidonic acid in the phospholipid fraction of the plerocercoids, increased compared with those of plerocercoids incubated at 37 C. The changes in the ratio of polyunsaturated to saturated fatty acids in the phospholipid fraction of plerocercoids incubated in physiological saline for 6 hr at 10 C were almost the same as the changes at 37 C. The ratio of polyunsaturated to saturated fatty acids of the triglyceride fraction showed almost opposite change versus the phospholipid fraction. The percentage of arachidonic acid in the phospholipid fraction of plerocercoids increased during the first 3 hr of incubation and then decreased, regardless of temperature. At 37 C, the percentage of arachidonic acid in the free fatty acid fraction fell for the first 3 hr of incubation and was significantly elevated at the end of the 6-hr incubation. At 10 C, however, arachidonic acid in the free fatty acid fraction decreased for the first hour of incubation, increased at 3 hr of incubation, then decreased again. These results suggest that fatty acids of the plerocercoids are frequently exchanged between fractions. Plerocercoids can mobilize arachidonic acid to the free fatty acid fraction more quickly at lower temperature than at higher temperature. They may utilize mobilized arachidonic acid early in the infection stage to produce prostaglandins. Alternatively, they can incorporate arachidonic acid into the phospholipid fraction again when arachidonic acid is readily available in the environment.

Animals↗

Effects of serum fractions obtained from cancer patients by double-filtration plasmapheresis on tumor growth and metastasis in mice.

We administered serum fractions obtained from cancer patients by double-filtration plasmapheresis (DFPP) to cancer-bearing mice to examine the effects on tumor growth and metastasis. Fraction 1 (whole plasma), fraction 2 (a plasma fraction containing substances with higher particle size), fraction 3 (a plasma fraction containing substances with smaller particle size) and saline were administered intravenously to cancer-bearing mice for 10 days following the inoculation of tumor cells. The tumor growth and metastasis in mice administered fraction 2 was far more rapid than that in the control mice. On the other hand, tumor growth in mice administered fraction 3 was significantly delayed compared with that in mice injected with fraction 2. These results suggest that factors in the higher particle-size fraction of cancer patients' sera promote the growth and the metastasis of tumors in mice, and that DFPP, which remove these factors, is an effective therapy against cancer.

Animals↗

Quantification of skeletal involvement in adults with type I Gaucher's disease: fat fraction measured by Dixon quantitative chemical shift imaging as a valid parameter.

OBJECTIVE: The objective of our study was to determine the merit of the fat fraction of axial bone marrow measured by Dixon quantitative chemical shift imaging (Dixon QCSI) as a clinical parameter to quantitatively assess the extent of skeletal involvement in type 1 Gaucher's disease. MATERIALS AND METHODS: Dixon QCSI was performed in 30 adult patients (age range, 18-69 years; mean, 39 years) with type 1 Gaucher's disease who were untreated. The relationship between the mean value of the fat fraction in vertebrae L3, L4, and L5 and the presence, absence, and severity of clinical bone complications (chronic bone pain, bone crisis, fracture, avascular necrosis, and joint replacement) as well as the conventional MR imaging of bone marrow involvement were studied. Also the relationship of fat fraction to sex, age, and other disease parameters (history of splenectomy, liver and spleen volume, plasma chitotriosidase, hemoglobin level, and platelet count) was evaluated. Our results were compared with the fat fraction of healthy volunteers. RESULTS: The fat fraction measured in patients with Gaucher's disease ranged from 0.08 to 0.40 (mean, 0.20). Bone complications occurred primarily in patients with a fat fraction of less than 0.23. Univariate logistic regression analysis indicated that for every decrease of 0.1 of the fat fraction, the risk of bone complications increased 85% (p < 0.05). The fat fraction was correlated with liver size, but no correlation with other disease parameters was found. In the patient population, the fat fraction was significantly lower than in the healthy population (range, 0.27-0.55; mean, 0.37; p < 0.001). CONCLUSION: The fat fraction of the lumbar spine when measured with Dixon QCSI is associated with the occurrence of bone complications. It may, therefore, be a clinically useful parameter.

Adipose Tissue↗

Rate and extent of digestion of the ethanol-soluble and neutral detergent-insoluble fractions of corn grain.

The objectives of this study were to partition corn grain into three digestible fractions and to measure the rate of disappearance of these fractions in vitro. Seventeen corn grain samples with varied fiber concentrations were extracted with either 80% ethanol or neutral detergent to obtain estimates of the pool size and digestion kinetics of the A, B1, B2, and C fractions. The carbohydrate soluble in 80% ethanol averaged only 2.6+/-.3% of the DM, although 80% ethanol extracted 7.1+/-1.2% of DM of corn grain. The ethanol-soluble fraction of corn grain contained protein, ether-extractable compounds, and a small amount of ash in addition to carbohydrate. Because of this chemical heterogeneity and because of the small size of the ethanol-soluble fraction, it was not possible to determine the digestion rate of this fraction by measuring gas production. The NDF content of the corn grain was 10.6+/-.7% of DM and was highly digestible (94.6+/-1.4%). The digestible NDF contributed 9.5% of the total gas production from corn grain. Because the size, digestibility, and digestion rate of the digestible NDF fraction varied little among corn grain samples, it is not necessary to routinely analyze the digestion kinetics of the digestible NDF fraction of dried corn grain. An average gas production curve of this fraction can be used as a base to subtract from the total gas production curve to generate the gas production curve of the neutral detergent-soluble fraction for dried, ground corn grain samples.

Detergents↗

Fractionation of fiber and crude protein in fresh forages during the spring growth.

The composition of the fiber and CP of alfalfa, bromegrass, and endophyte-free and -infected tall fescue forages was compared during the spring growth from vegetative to reproductive stages. Forages were sampled from April 27 to June 6 in 1994, and from April 27 to June 11 in 1995, with 11 and 12 harvest dates, respectively. Total dietary fiber (TDF) was fractionated into insoluble and soluble fiber (SF). The CP of the forages was fractionated into nonprotein N (A), soluble CP (B1), insoluble CP that was soluble in neutral detergent (B2), CP insoluble in neutral detergent but soluble in acid detergent (B3), and CP insoluble in acid detergent (C). Effects of year, forage species, and harvest dates (day as a covariable) were included in the model. Across harvest dates, alfalfa (A) had lower (P < .01) TDF and higher (P < .01) SF concentrations than grasses (GR) (A: 49.9 and 14.4% and GR: 60.4 and 4.5% [OM basis] for TDF and SF, respectively). Alfalfa had higher (P < .01) CP (20.6% DM) than GR (15.3%). The rate of decrease in CP (% DM) across days was higher (P < .01) for bromegrass (-.4%/d) than for the other forages (-.29%/d). Fraction A (% of CP) was not different (P = .24) among forages (22.5%), but B1 was higher (P < .01) in A (17.1%) than in GR (13.2%). The B2 fraction (% of CP) was higher (P < .01) in A compared with GR (51.6 vs 45.9%, respectively). Alfalfa had lower (P < .01) B3 (3.0% of CP) than bromegrass (18.6%) and tall fescue (13.2%). Fraction C was not different (P = .23) among forages (3.8%). Fractions A, B1, and C (% of CP) did not change (P > .05) across days for all forages. Fraction B2 (% of CP) decreased across days in A (-.21%/d) but was not affected in GR. Fraction B3 (% of CP) increased (P < .05) in A (.1%/d), decreased in endophyte-infected tall fescue (-.20%/d), and did not change (P > .05) in the other forages. Crude protein and fiber composition were affected more by forage species than by maturity. The CP and NDF concentrations were more affected by maturity. Insoluble fractions but not soluble fractions of CP were affected by maturity.

Animal Feed↗

Crude protein fractions in common vetch (Vicia sativa L.) fresh forage during pod filling.

Crude protein (CP) of forages can be separated into fractions of differentiated abilities to provide available amino acids in the lower gut of ruminants. This knowledge is critical to develop feeding systems and to predict animal responses. We have measured during two growing seasons (1996 to 1997 and 1997 to 1998) the CP fractions of common vetch fresh forage with the objective being to assess the influence of maturity on concentration of CP fractions (as a percentage of total CP) and fraction yields. Fraction B2, which represents true protein of intermediate ruminal degradation rate, was the largest single fraction in common vetch forage (about 40% of CP across seasons and maturity stages). Soluble fractions (A plus B1) were less than 50% of total CP while the unavailable fraction C ranged from 4 to 8% of total CP. As a result, the remaining fraction B3 (true protein of very low degradation rate) only represented 2 to 9% of total CP. Concentration and yield of fraction B3 increased (P < 0.05) from flowering to pod-filling. Results showed that undegraded dietary protein represented a small proportion of total CP in common vetch forage. Moving the harvesting stage from flowering to the pod filling phase allowed for greater yield of undegraded dietary protein.

Animal Feed↗

Influence of fraction size on the development of late radiation enteropathy. An experimental study in the rat.

The use of large fraction sizes in radiotherapy may be associated with an increased risk of complications from late responding normal tissues. However, in the intestine, chronic injury may develop either as primary late effect or secondary to disruption of mucosal integrity as so-called consequential injury. Mucosal damage is relatively less sensitive to changes in fraction size than late reacting, slowly proliferating cells. The relationship between fraction size and chronic radiation enteropathy in a given situation may thus depend on which of the two mechanisms that predominates. Most previous studies of the influence of fraction size on radiation injury are confounded by differences in treatment time. The present study was therefore designed to assess subacute and chronic radiation enteropathy after three different fractionation regimens where fraction size was the only experimental variable. A total of 96 male Sprague-Dawley rats were orchiectomized and a functionally intact loop of small intestine was transposed into the left scrotum. These 'scrotal hernias' containing intestine were subsequently exposed to 50.4 Gy localized fractionated irradiation over 18 days with either 2.8 Gy every 24 h, 4.2 Gy every 36 h, or 5.6 Gy every 48 h. Control animals were sham irradiated. The animals were observed for development of intestinal complications (intestinal obstruction or enterocutaneous fistula formation) up to 6 months after irradiation. Histologic damage was assessed in groups of animals at 2 weeks (subacute injury) and 26 weeks (chronic injury), using a previously validated radiation injury score (RIS). RIS increased significantly with increasing fraction size at both observation times. However, the increase was more pronounced at 26 weeks than at 2 weeks. Increased chronic injury was characterized by increased incidence and severity of mucosal ulceration, serosal thickening, vascular sclerosis and intestinal wall fibrosis. We conclude that increasing fraction size increases both subacute and, even more markedly, chronic injury in the intestine. With the fractionation regimens used here, the chronic radiation enteropathy develops as a combined consequential and primary late effect, but the primary mechanism predominates.

Acute Disease↗

Malondialdehyde formation in liver mitochondrial and microsomal fractions of vitamin E- and selenium-deficient rats as a function of alpha-tocopherol level: the effect of treatment in vitro with iron.

Weanling rats were given diets with adequate vitamin E and selenium or deprived of one or the other or both, nutrients. After 28 days, liver mitochondrial and microsomal fractions were prepared and alpha-tocopherol (alpha-T) and selenium measured. alpha-Tocopherol fell by eight-fold in the doubly deficient rats and selenium fell three-fold. Malondialdehyde (MDA) was found to be undetectable by a sensitive HPLC method. The fractions were subjected to peroxidative stress in in vitro using 0.5 mM Fe2+/10 mM ADP, and MDA and alpha-T were measured at intervals during 30 min. The results showed that in the mitochondrial fractions there was a lag time of at least 2 min before peroxidation became significant, during which time most of the alpha-T was consumed. In the microsomal fraction the lag phase was very short prior to the establishment of a linear rate of peroxidation, although little alpha-T was used up. It was concluded that the mitochondrial fraction withstood the peroxidative challenge better than the microsomal fraction even though the initial level of alpha-T in the microsomal fraction was about double that in the mitochondrial fraction. Selenium deficiency had no effect on the length of the lag phase of the fractions which therefore appears to be a characteristic of mitochondrial or microsomal fractions.

Adenosine Diphosphate↗

Radiosurgery and fractionated radiation therapy: comparison of different techniques in an in vivo rat glioma model.

To identify histological changes and effects on survival in rats harboring C6 gliomas, the authors compared radiosurgery to different fractionated radiation therapy regimens including doses of calculated biological equivalence. Rats were randomized to control (54 animals) or treatment groups after implantation of C6 glioma cells into the right frontal brain region. At 14 days, treated rats underwent stereotactic radiosurgery (35 Gy to tumor margin; 22 animals), whole-brain radiation therapy (WBRT) (20 Gy in five fractions; 18 animals), radiosurgery plus WBRT (13 animals), hemibrain radiation therapy (85 Gy in 10 fractions; 16 animals) or single-fraction hemibrain irradiation (35 Gy; 10 animals). When compared to the control group (median survival 22 days), prolonged survival was identified after radiosurgery (p < 0.0001), radiosurgery plus WBRT (p < 0.0001), WBRT alone (p = 0.0002), hemibrain radiation therapy to 85 Gy (p < 0.0001), and 35-Gy hemibrain single-fraction irradiation (p = 0.004). Compared to the control group (mean tumor diameter, 6.8 mm), the tumor size was reduced in all treatment groups except WBRT alone. Reduced tumor cell density was exhibited in rats that underwent radiosurgery (p = 0.006) and radiosurgery plus WBRT (p = 0.009) when compared with rats in the control group, a finding not observed after any fractionated regimen. Increased intratumoral edema was identified after radiosurgery (p = 0.03) and combined treatment (p = 0.05), but not after fractionated radiation therapy or 35-Gy single-fraction hemibrain irradiation. In this animal model, the addition of radiosurgery significantly increased tumor cytotoxicity, potentially at the expense of radiation effects to regional brain. We found no difference in survival benefit or tumor diameter in animals that underwent radiosurgery compared to the calculated biologically equivalent regimen of 10-fraction radiation therapy to 85 Gy. The histological responses after radiosurgery were generally greater than those achieved with biologically equivalent doses of fractionated radiation therapy.

Animals↗