Molecular detection of cosaviruses in a patient with acute flaccid paralysis and in sewage samples in Germany.

Cosaviruses (CoSV) were first identified in stool samples collected from non-polio acute flaccid paralysis (AFP) cases and their healthy contacts in Pakistan in 2003. The clinical importance of CoSV remains unclear as data on epidemiology are scarce and no routine diagnostic testing is done. In this study, we characterized human CoSV (HCoSV) in a child with non-polio AFP and in sewage samples collected in Berlin, Germany. Using unbiased high-throughput sequencing and specific PCR, we characterized a HCoSV-D in stool samples of a three-year-old child hospitalized in Germany with non-polio AFP and travel history to Pakistan. The shedding pattern and absence of other relevant pathogens suggests that HCoSV-D may have been involved in the genesis of AFP. The HCoSV-RNA concentration was high, with 2.57 × 106 copies per mL fecal/suspension, decreasing in follow-up samples. To investigate the possibility of local circulation of HCoSV, we screened Berlin sewage samples collected between 2013 and 2018. Molecular testing of sewage samples has shown the presence of CoSV in several parts of the world, but until now not in Germany. Of our sewage samples, 54.3 % were positive for CoSV, with up to three viral species identified in samples. Phylogenetically, the German sequences clustered intermixed with sequences obtained globally. Together, these findings emphasize the need for further clinical, epidemiological, environmental, pathogenicity and phylogenetic studies of HCoSV.

Historical development of root analogue implants: a review of published papers.

The timetable for placing a dental implant can be crucial in the reduction of resorption of the socket after an extraction. The association of immediate implantation with an implant that copies the anatomy of the extracted root seems to add benefits in limiting the hard and soft tissue changes that may occur. The purpose of this paper is to provide an overview of the historical development of all types of root analogue implants from their beginning to the present day. To our knowledge the first individualised ones were described in 1969. Later, the use of titanium instead of the polymers that were used to start with offered better bony integration, and showed that the selection of materials was a key factor in their success. Root analogue implants made from zirconia were also described when attempts were being made to improve aesthetics in the anterior regions. The more recent introduction of digital technology such as DICOM has allowed the fabrication of these implants in less time, and the combination with digital diagnostic options such as cone-beam computed tomography facilitated the fabrication of some types of implants before extraction that could be inserted immediately into the alveolar socket with optimal and safe 3-dimensional positioning. Currently digital planning allows the clinician to design the ideal implant and abutment, which reduces the need for tissue grafting in the surgical phase and gingival conditioning in the prosthetic phase.

Impacts of a leptin SNP on growth performance and carcass characters in finishing steers studied over time.

A total of 2,948 steers (mean initial BW = 568.9 ± 49.4 kg) were used to evaluate the effect of the LEP R25C SNP genotype on feed intake, growth performance, and carcass characteristics over time. Steers were grouped into 5 blocks, each consisting of 10 pens initially, and then at approximately 24 d prior to the assigned slaughter date, cattle in each pen were randomly selected either to remain in the pen they were in (group A) or to be assigned to a new pen (group B). Steers were allocated to 5 blocks and 6 harvest weeks (-3, -2, 0, 2, 3, and 4 wk) relative to the projected end point. Steers were weighed and ultrasound scanned at 60 and 1 d prior to harvest. Leptin genotype affected ( ≤ 0.011) 12th-rib fat and i.m. fat percentage (IMF) for each slaughter group at both 60 and 1 d prior to slaughter, although rib eye area (REA) was not affected ( = 0.773) by leptin genotype 60 d prior to slaughter in any group. Time affected ( < 0.001) live BW as well as 12th-rib fat, REA, and IMF measured 60 and 1 d prior to each slaughter time. Dry matter intake was also higher ( = 0.003) for cattle of the animals homozygous for the T allele (TT) genotype compared to those with the animals homozygous for the C allele (CC) genotype (9.59 vs. 9.29 ± 0.075 kg). The LEP R25C genotype affected key traits related to carcass fatness; specifically, compared to cattle of the CC genotype, cattle of the TT genotype had a higher ( = 0.016) calculated empty body fat (29.1 vs. 28.8 ± 0.133%) and higher ( = 0.020 calculated yield grade (2.62 vs. 2.52 ± 0.035). Additionally, like for live measures, TT cattle tended ( = 0.093) to have a higher 12th-rib fat (13.2 vs. 12.8 ± 0.26 mm). However, the LEP R25C genotype did not affect KPH ( = 0.854) or marbling score ( = 0.240), nor did it affect any USDA quality measure ( ≥ 0.350). The leptin genotype also affected ( = 0.048) HCW, which was highest for steers of the TT genotype (400.9 vs. 403.5 ± 3.41kg). Results indicate that the leptin R25C genotype and time impacted most traits associated with fatness.

Impact of a leptin single nucleotide polymorphism and ractopamine hydrochloride on growth and carcass characteristics in finishing steers.

A total of 2,958 steers (mean initial BW = 549.6 ± 3.88 kg) were used to test for the interactive effects, of leptin R25C genotypes (CC, CT, or TT) and feeding of ractopamine hydrochloride (RH) on growth performance and carcass traits. Before application of the drug, steers were blocked by arrival at the feed yard, genotyped for the leptin SNP, allotted to genotype-specific pens, and assigned randomly within genotype and block to 0 or 28 d of dietary RH. All pens within a block were slaughtered on the same day. Final BW of steers fed RH was 9.1 kg heavier (P < 0.001), and RH-fed steers had greater (P < 0.001) ADG and greater (P = 0.001) HCW than steers not fed RH. Feeding RH did not (P = 0.723) affect DMI but it did increase (P = 0.001) with increased frequency of the T allele (8.62, 8.70, and 8.82 kg/d for CC, CT, and TT, respectively). Consistent with the effect of leptin on DMI, increased frequency of the T allele also positively affected 12th rib fat (P = 0.001) and empty body fat (P = 0.001). Regardless of RH-feeding duration, TT steers produced a greater (P = 0.001) percentage of USDA yield grade (YG) 4 or higher carcasses (6.46 vs. 2.98%) and a lesser (P = 0.023) percentage of YG 1 carcasses (16.0 vs. 21.9%) than CC steers. In addition, RH-fed steers produced a lesser (P = 0.034) percentage of USDA YG 4 or higher carcasses (3.70 vs. 5.31%) and a lesser percentage (P = 0.019) of USDA Choice or higher carcasses (57.5 vs. 62.5%) than steers fed the control diet. Results indicated that leptin R25C genotype impacted most traits associated with fatness, whereas feeding RH for 28 d affected HCW and ADG positively but impacted marbling and USDA quality grades negatively.

Impact of a leptin single nucleotide polymorphism and zilpaterol hydrochloride on growth and carcass characteristics in finishing steers.

A total of 4,178 steers (mean initial BW = 403.9 ± 16.04 kg) were used to test the interactive effects, if any, of leptin R25C genotypes (CC, CT, or TT) and zilpaterol hydrochloride (ZH) feeding duration on growth performance and carcass traits. Steers were blocked by arrival at the feed yard, genotyped for the leptin SNP, allotted to genotype-specific pens (90 steers/pen), and assigned randomly within genotype and block to 0 or 21 d of dietary ZH. All pens within a block were slaughtered on the same day (132.1 ± 10.9 d on feed). Final BW of steers fed ZH was 6.0 kg heavier (P = 0.008), and ZH-fed steers had greater (P = 0.003) ADG than steers not fed ZH. Feeding ZH decreased DMI in steers with increased frequency of the T allele (9.67, 9.53, and 9.28 kg/d for CC, CT, and TT, respectively), but DMI increased with the frequency of the T allele (9.68, 9.90, and 10.1 kg for CC, CT, and TT, respectively) when ZH was not fed (leptin genotype × ZH, P = 0.011). At the conclusion of the study, ultrasonic fat was greatest for TT steers (11.4 ± 0.28 mm) and least (P = 0.003) for CC steers (11.0 ± 0.25 mm). Regardless of ZH-feeding duration, TT steers produced a greater (P = 0.006) percentage of USDA yield grade (YG) 4 or higher carcasses (5.4 vs. 2.7%) and a lesser (P = 0.006) percentage of YG 1 carcasses (17.7 vs. 26.8%) than CC steers. In addition, ZH-fed steers produced a greater (P < 0.001) percentage of USDA YG 1 carcasses (25.9 vs. 16.2%) and a lesser (P < 0.001) percentage of YG 4 or higher carcasses (1.6 vs. 6.0%) than steers fed the control diet. Marbling scores and the percentage of carcasses grading USDA Choice and Prime were greater in TT than CC steers when fed diets devoid of ZH, but both marbling and quality grades did not differ among leptin genotypes when fed ZH for 21 d (leptin genotype × ZH, P ≤ 0.03). The amount of HCW gain tended to be less (P = 0.095) for steers of the TT genotype (12.7 kg) than either CC (16.3 kg) or CT (17.0 kg) genotypes. Results indicated that leptin R25C genotype impacted most traits associated with fatness whereas feeding ZH for 21 d affected HCW and ADG positively but impacted feed intake, marbling, and USDA quality grades negatively.

Effect of ractopamine HCl supplementation on fecal shedding of Escherichia coli O157:H7 and Salmonella in feedlot cattle.

The effects of the beta-agonist ractopamine, recently approved for use in feedlot cattle to improve carcass quality and performance, on fecal shedding Escherichia coli O157:H7 and Salmonella in feedlot cattle was examined. In the first study, 20 feedlot steers and heifers were randomly assigned to receive ractopamine or no ractopamine (control) by way of oral bolus for 28 days. Fecal samples were collected daily, and shedding of E. coli O157:H7 determined. When examined during the entire 28-day experimental period, ractopamine decreased (P = 0.0006) the percentage of cattle shedding E. coli O157:H7 (58% vs. 42% for control and ractopamine treatments, respectively). A second study was conducted in a commercial feedlot facility in the southwestern United States. Eighteen pens of cross-bred beef heifers (approximately 100 head/pen and 9 pens/treatment) were randomly assigned to receive either 0 (control) or 200 mg ractopamine/head x d(-1). Fresh fecal samples (30/pen) were collected off the pen floor before ractopamine supplementation and again after approximately 28 days of ractopamine supplementation (within a few days of slaughter); the samples were cultured for E. coli O157:H7 and Salmonella. The percentage of animals shedding E. coli O157:H7 was decreased when data were pooled across replicates (P = 0.05) in ractopamine-treated cattle compared with controls. The percentage of animals shedding Salmonella tended to be higher (P = 0.08) with the ractopamine treatment when data were pooled across replicates. Although further research is required to confirm these results, the potential food safety implications of this research are intriguing.

Fecal prevalence of Escherichia coli O157, Salmonella, Listeria, and Bacteriophage Infecting E. coli O157:H7 in feedlot cattle in the Southern Plains region of the United States.

Escherichia coli O157:H7, Salmonella, and Listeria are foodborne pathogens of critical importance that often colonize cattle. E. coli O157:H7 can be specifically killed by lytic bacteriophage, and lytic bacteriophage treatment has been suggested as a pre-harvest intervention strategy to reduce foodborne pathogens in cattle. To date, no systematic approach to determine the incidence of E. coli O157:H7-infecting lytic bacteriophage has been published. Therefore, the current study was designed to determine (1) the incidence of E. coli O157, Salmonella spp., and Listeria and (2) the incidence of E. coli O157:H7-infecting bacteriophage in the feces of feedlot steers in commercial feedlots in the United States. Fecal samples (n=60) were collected from four feedlots in two Southern Great Plains states (total (n=240 fecal samples). Salmonella and E. coli O157:H7 were found in 3.8% and 11.7% of the fecal samples, respectively. Bacteriophage targeting E. coli O157:H7 were found in all four feedlots, in 15% of the individual fecal samples, and in 55% of the cattle pens. Our results indicate that such bacteriophage are widespread in feedlot cattle, suggesting that further research into the ecological role of bacteriophage in the gastrointestinal tract is needed.

Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study.

OBJECTIVE: The primary objective of this study was to determine whether the National Cholesterol Education Program Step II (NCEP-II) diet or supplementation with docosahexaenoic acid (DHA) with the diet, affects endothelial function in children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). As secondary endpoints, the influence of diet and DHA supplementation on lipid profiles as well as biomarkers for oxidative stress and inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, were all evaluated. METHODS: In a double-blind, placebo-controlled, randomized, crossover study design, 20 children (ages 9-19 years) with FH (n = 12) and FCH (n = 8) received nutritional counseling based on the National Cholesterol Education Program Step II (NCEP-II) and food guide pyramid dietary guidelines for 6 weeks. They were then randomly assigned to supplementation with docosahexaenoic acid (DHA 1.2 g/d) or placebo for 6 weeks, followed by a washout phase of 6 weeks and crossover phase of 6 weeks while continuing the NCEP-II diet. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was determined by high-resolution ultrasound. Plasma levels of total cholesterol, triglycerides and lipoprotein classes (LDL, HDL, VLDL) were measured by ultracentrifugation and enzymatic methods, plasma F2 isoprostanes by gas chromatography/mass spectrometry, urinary 8-OH-2' deoxyguanosine by liquid chromatography, high sensitivity C-reactive protein by immunonephelometry and ADMA by liquid chromatography. RESULTS: FMD increased significantly after DHA supplementation compared to baseline (p < 0.001), diet alone (p < 0.002), placebo (p < 0.012) and washout (p < 0.001) phases of the study without affecting biomarkers for oxidative stress, inflammation or ADMA. DHA supplementation was associated with increased levels of total cholesterol (p < 0.01), LDL- and HDL cholesterol concentrations (p < 0.001) compared to the NCEP-II diet. CONCLUSION: This study demonstrates that DHA supplementation restores endothelial-dependent FMD in hyperlipidemic children. The endothelium may thus be a therapeutic target for DHA. This is consistent with a hypothesis of increasing NO bioavailability, with the potential for preventing the progression of early coronary heart disease in high-risk children.

A formalism for independent checking of Gamma Knife dose calculations.

For stereotactic radiosurgery using the Leksell Gamma Knife system, it is important to perform a pre-treatment verification of the maximum dose calculated with the Leksell GammaPlan (DLGP) stereotactic radiosurgery system. This verification can be incorporated as part of a routine quality assurance (QA) procedure to minimize the chance of a hazardous overdose. To implement this procedure, a formalism has been developed to calculate the dose DCAL(X,Y,Z,dav,t) using the following parameters: average target depth (dav), coordinates (X,Y,Z) of the maximum dose location or any other dose point(s) to be verified, 3-dimensional (3-dim) beam profiles or off-centerratios (OCR) of the four helmets, helmet size i, output factor Oi, plug factor Pi, each shot j coordinates (x,y,z)i,j, and shot treatment time (ti,j). The average depth of the target dav was obtained either from MRI/CT images or ruler measurements of the Gamma Knife Bubble Head Frame. DCAL and DLGP were then compared to evaluate the accuracy of this independent calculation. The proposed calculation for an independent check of DLGP has been demonstrated to be accurate and reliable, and thus serves as a QA tool for Gamma Knife stereotactic radiosurgery.

Comparison of radiobiologic modeling for one- and two-isocenter dose distributions applied to ellipsoidal radiosurgery targets.

PURPOSE: RTOG protocol 90-05 determined the maximum acutely tolerated dose of single-fraction radiosurgery in patients receiving prior fractionated large volume cranial irradiation. Data from 90-05 have suggested that patients treated with a gamma unit, compared to linac-based therapy, have a tumor control advantage and lower rates of severe complications. This study was performed to investigate the radiobiologic effect of using one vs. two isocenters in single-fraction radiosurgery of ellipsoidal targets. METHODS AND MATERIALS: For a series of ellipsoidal targets that varied by volume and radiosensitivity, single and two-isocenter treatment plans were generated to approximate those typically employed for gamma unit and linac radiosurgery. Tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) were generated automatically by the treatment planning system based on established parameter values. RESULTS: The modeling data showed that multiple-isocenter plans resulted in improved TCP with equivalent or lesser NTCP, particularly for larger, radioresistant targets. Multiple-isocenter plans reduce the amount of normal tissue that receives high dose. Also, areas within the tumor receive significantly higher doses than the prescription dose, which contributes to increased tumor cell inactivation. CONCLUSION: For ellipsoidal targets, radiobiologic modeling data are consistent with the clinical findings of the RTOG 90-05 trial, as they predict improved outcome with a multiple-isocenter plan relative to a single-isocenter plan. The benefit is most apparent with increasing target volume and decreasing tumor radiosensitivity.

Dependence of linac output on the switch rate of an intensity-modulated tomotherapy collimator.

The electro-mechanical, multivane intensity modulated collimator ("MIMiC") slit collimator with 40 vanes has been applied in the delivery of inversely planned sequential tomotherapy to over 4,000 patients. The collimator is binary in that each vane switches between fully open or closed status. Resulting beamlet patterns provide the intensity distributions imparting dose to the patient. The bouncing and damping of vanes at the two ends of their travel cause transient dose perturbations near and at the borders of the treatment field. These perturbations are not explicitly modeled by the planning system. Clinical beamlet profiles and output factors may then differ from those in the planning system and as a function of the vane switch period. A mechanical model of vane switching was developed to describe this dependency. Dose output and distribution of seven simple vane patterns with different switch times were measured with ionization chambers and radiographic films in polystyrene and anthropomorphic phantoms. Linac output dependence on switch time relative to vane open time was determined for four intensity modulated radiotherapy (IMRT) patients from measurements of an ionization chamber embedded in a cylindrical polystyrene phantom. Results demonstrate output dependence on switch time and, accordingly, on the servo mechanism for monitor units, arc length, dose rate, and gantry speed. In conclusion, the output dependence borders on clinical significance-improvements to collimator, dose calculation, commissioning, and quality assurance (QA) are suggested.

Soluble epoxide hydrolase regulates hydrolysis of vasoactive epoxyeicosatrienoic acids.

The cytochrome P450-derived epoxyeicosatrienoic acids (EETs) have potent effects on renal vascular reactivity and tubular sodium and water transport; however, the role of these eicosanoids in the pathogenesis of hypertension is controversial. The current study examined the hydrolysis of the EETs to the corresponding dihydroxyeicosatrienoic acids (DHETs) as a mechanism for regulation of EET activity and blood pressure. EET hydrolysis was increased 5- to 54-fold in renal cortical S9 fractions from the spontaneously hypertensive rat (SHR) relative to the normotensive Wistar-Kyoto (WKY) rat. This increase was most significant for the 14,15-EET regioisomer, and there was a clear preference for hydrolysis of 14, 15-EET over the 8,9- and 11,12-EETs. Increased EET hydrolysis was consistent with increased expression of soluble epoxide hydrolase (sEH) in the SHR renal microsomes and cytosol relative to the WKY samples. The urinary excretion of 14,15-DHET was 2.6-fold higher in the SHR than in the WKY rat, confirming increased EET hydrolysis in the SHR in vivo. Blood pressure was decreased 22+/-4 mm Hg (P:<0.01) 6 hours after treatment of SHRs with the selective sEH inhibitor N:, N:'-dicyclohexylurea; this treatment had no effect on blood pressure in the WKY rat. These studies identify sEH as a novel therapeutic target for control of blood pressure. The identification of a potent and selective inhibitor of EET hydrolysis will be invaluable in separating the vascular effects of the EET and DHET eicosanoids.

Dietary docosahexaenoic acid affects stearic acid desaturation in spontaneously hypertensive rats.

Docosahexaenoic acid (DHA, 22:6n-3) is an n-3 polyunsaturated fatty acid which attenuates the development of hypertension in spontaneously hypertensive rats (SHR). The effects of DHA on delta-9-desaturase activity in hepatic microsomes and fatty acid composition were examined in young SHR. Two groups of SHR were fed either a DHA-enriched diet or a control diet for 6 wk. Desaturase activity and fatty acid composition were determined in hepatic microsomes following the dietary treatments. Delta-9-desaturase activity was decreased by 53% in DHA-fed SHR and was accompanied by an increase in 16:0 and a reduction in 16:1n-7 content in hepatic microsomes. The DHA diet also increased the levels of eicosapentaenoic acid (20:5n-3) and DHA. The n-6 fatty acid content was also affected in DHA-fed SHR as reflected by a decrease in gamma-linolenic acid (18:3n-6), arachidonic acid (20:4n-6), adrenic acid (22:4n-6), and docosapentaenoic acid (22:5n-6). A higher proportion of dihomo-gamma-linolenic acid (20:3n-6) and a lower proportion of 20:4n-6 is indicative of impaired delta-5-desaturase activity. The alterations in fatty acid composition and metabolism may contribute to the antihypertensive effect of DHA previously reported.

Mechanisms of vasorelaxation induced by eicosapentaenoic acid (20:5n-3) in WKY rat aorta.

The vasorelaxant activity of eicosapentaenoic acid (EPA, 20:5n-3), the omega-3 polyunsaturated fatty acid, was investigated in isolated Wistar Kyoto (WKY) rat aortae by measuring isometric tension. Eicosapentaenoic acid (1 - 100 microM) relaxed rat aortae contracted with high K(+) (80 mM) or noradrenaline (NA, 1 microM) in a concentration-dependent manner. Contractions induced by Bay K 8644 or increasing concentrations of calcium were unaffected by EPA. The relaxant effect of EPA (3 - 100 microM) was significantly inhibited by indomethacin (10 microM), the cyclo-oxygenase inhibitor, but not by the nitric oxide (NO) synthesis inhibitor, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 microM). Removal of the endothelium did not alter EPA-induced relaxations. In Ca(2+)-free, EGTA 2 mM solution, EPA (10 - 30 microM significantly inhibited NA-sustained contractions. Incubation with EPA (5, 10 microM) diminished both NA-induced (1 microM) phasic and sustained contractions. The vasorelaxant effects of EPA (> or =30 microM) on NA-induced (1 microM) contractions were significantly inhibited by the K(+) channel blocker, glibenclamide (10 microM), but not tetraethylammonium (1 mM). Moreover, indomethacin and glibenclamide combined significantly inhibited EPA-induced (1 - 100 microM) responses. These results indicate EPA exerts its endothelium-independent vasorelaxant effects in WKY rat aortae through production of prostanoids which activate K(+)(ATP) channels. Inhibition of Ca(2+) mobilization from intracellular pools and influx through the non-L-type, but not the L-type, Ca(2+) channel are also possible mechanisms action of EPA's.

Docosahexaenoic acid--induced vasorelaxation in hypertensive rats: mechanisms of action.

The authors investigated the vasorelaxant properties of the omega-3 fatty acid, docosahexaenoic (DHA, 22:6n-3), and the possible involvement of endothelium-derived nitric oxide, prostanoids, opening of K+ channels, and/or modulation of calcium-mediated events. Isolated aorta from male spontaneously hypertensive rats (SHR) (age 16-17 weeks) were used to measure isometric tension. DHA-induced (1-100 mumol/l) relaxation was examined following contraction to norepinephrine (NE) (10(-6) mol/l) or high-K+ (80 mmol/l) solution in the presence and absence of various inhibitors and calcium-containing solution. DHA acid induced a significant vasorelaxant effect in both NE and high-K(+)-induced contracted SHR aortic rings, although DHA relaxations were greater in high-K(+)-induced contracted rings. In the absence of extracellular calcium, DHA (5-30 mumol/l) inhibited the initial phasic and sustained components of NE-induced contraction under different conditions. Inhibition of nitric oxide synthesis by N omega-nitro-L-arginine methyl ester hydrochloride (100 mumol/l) had no effect on DHA relaxations; however, indomethacin or nifedipine caused significant inhibition at > or = 30 mumol/l DHA. The K+ channel blocker, glibenclamide, but not tetraethyl-ammonium, also had an inhibitory effect on DHA-induced relaxation. These results indicate that DHA's vasorelaxant actions in SHR aorta are independent of endothelium-derived nitric oxide; however, at DHA concentrations > or = 30 mumol/l, vasodilatory prostanoids that activate ATP-sensitive K+ channels (KATP) may be involved. At lower concentrations, DHA-induced relaxation appears to be attributed to modulation of intracellular Ca2+ release and L-type Ca2+ channels in vascular smooth muscle cells. The vasorelaxant properties of DHA may contribute, in part, to the blood pressure-lowering effect of dietary fish oil in this hypertensive model.

Docosahexaenoic acid is an antihypertensive nutrient that affects aldosterone production in SHR.

The effects of dietary docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, on blood pressure and some pressure-regulating systems were measured in young spontaneously hypertensive rats (SHR). Plasma aldosterone and corticosterone levels, adrenal aldosterone production in vitro, and characteristics of adrenal angiotensin receptors were measured after 6 weeks of diet. Renal cytochrome P450 (CYP) 4A gene expression and arachidonic acid metabolism by renal microsomes were also investigated. Plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured. Diets contained either corn/soybean oil alone (CSO), or oil enriched with DHA. After 6 weeks, rats fed DHA had systolic blood pressures averaging 34 mmHg less than controls (P < 0.001). Plasma aldosterone levels were 33% lower in the DHA-fed animals than in controls (22 +/- 3 vs. 33 +/- 3.7 ng/dl, P < 0.05). Plasma levels of corticosterone were 18% lower in animals fed DHA than in controls, but this difference was not statistically significant. Adrenal glomerulosa cells from DHA-fed rats produced less aldosterone in vitro in response to angiotensin II, ACTH, or potassium. The difference was less marked when aldosterone production was stimulated by supplying exogenous corticosterone, suggesting an effect of DHA on postreceptor steps in signal transduction or the early pathway of aldosteronogenesis. We found no significant differences in angiotensin receptor subtype, number, or affinity. Production of arachidonic epoxides by renal microsomes was 17% lower in DHA-fed animals than in controls (P < 0.05). Renal cortical mRNA levels of CYP4A genes and formation of 19- and 20-hydroxyeicosatetraenoic acid (HETE) did not differ between dietary groups. Plasma total cholesterol and high-density-lipoprotein (HDL) levels were significantly reduced in SHR fed the DHA supplement, but triglyceride levels were not significantly different. The effects of DHA on steroid and eicosanoid metabolism may be part of the mechanism by which this fatty acid prevents some of the hypertension in growing SHR.

A non-invasive immobilization system and related quality assurance for dynamic intensity modulated radiation therapy of intracranial and head and neck disease.

PURPOSE: To develop and implement a non-invasive immobilization system guided by a dedicated quality assurance (QA) program for dynamic intensity-modulated radiotherapy (IMRT) of intracranial and head and neck disease, with IMRT delivered using the NOMOS Corporation's Peacock System and MIMiC collimator. METHODS AND MATERIALS: Thermoplastic face masks are combined with cradle-shaped polyurethane foaming agents and a dedicated quality assurance program to create a customized headholder system (CHS). Plastic shrinkage was studied to understand its effect on immobilization. Fiducial points for computerized tomography (CT) are obtained by placing multiple dabs of barium paste on mask surfaces at intersections of laser projections used for patient positioning. Fiducial lines are drawn on the cradle along laser projections aligned with nasal surfaces. Lateral CT topograms are annotated with a crosshair indicating the origin of the treatment planning and delivery coordinate system, and with lines delineating the projections of superior-inferior field borders of the linear accelerator's secondary collimators, or with those of the fully open MIMiC. Port films exposed with and without the MIMIC are compared to annotated topograms to measure positional variance (PV) in superior-inferior (SI), right-left (RL), and anterior posterior (AP) directions. MIMiC vane patterns superposed on port films are applied to verify planned patterns. A 12-patient study of PV was performed by analyzing positions of 10 anatomic points on repeat CT topograms, plotting histograms of PV, and determining average PV. RESULTS AND DISCUSSION: A 1.5+/-0.3 mm SD shrinkage per 70 cm of thermoplastic was observed over 24 h. Average PV of 1.0+/-0.8, 1.2+/-1.1, and 1.3+/-0.8 mm were measured in SI, AP, and RL directions, respectively. Lateral port films exposed with and without the MIMiC showed PV of 0.2+/-1.3 and 0.8+/-2.2 mm in AP and SI directions. Vane patterns superimposed on port films consistently verified the planned patterns. CONCLUSION: The CHS provided adequately reproducible immobilization for dynamic IMRT, and may be applicable to decrease PV for other cranial and head and neck external beam radiation therapy.