Impact of Interfractional Bladder and Trigone Displacement and Deformation on Radiation Exposure and Subsequent Acute Genitourinary Toxicity: A Post Hoc Analysis of Patients Treated with Magnetic Resonance Imaging-Guided Prostate Stereotactic Body Radiation Therapy in a Phase 3 Randomized Trial.

PURPOSE: Emerging data suggest that trigone dosimetry may be more associated with poststereotactic body radiation therapy (SBRT) urinary toxicity than whole bladder dosimetry. We quantify the dosimetric effect of interfractional displacement and deformation of the whole bladder and trigone during prostate SBRT using on-board, pretreatment 0.35T magnetic resonance images (MRI). METHODS AND MATERIALS: Seventy-seven patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) on the MRI arm of a phase 3 single-center randomized trial were included. Bladder and trigone structures were contoured on images obtained from a 0.35T simulation MRI and 5 on-board pretreatment MRIs. Dice similarity coefficient (DSC) scores and changes in volume between simulation and daily treatments were calculated. Dosimetric parameters including Dmax, D0.03 cc, Dmean, V40 Gy, V39 Gy, V38 Gy, and V20 Gy for the bladder and trigone for the simulation and daily treatments were collected. Both physician-scored (Common Terminology Criteria for Adverse Events, version 4.03 scale) as well as patient-reported (International Prostate Symptom Scores and the Expanded Prostate Cancer Index Composite-26 scores) acute genitourinary (GU) toxicity outcomes were collected and analyzed. RESULTS: The average treatment bladder volume was about 30% smaller than the simulation bladder volume; however, the trigone volume remained fairly consistent despite being positively correlated with total bladder volume. Overall, the trigone accounted for <2% of the bladder volume. Median DSC for the bladder was 0.79, whereas the median DSC of the trigone was only 0.33. No statistically significant associations between our selected bladder and trigonal dosimetric parameters and grade ≥2 GU toxicity were identified, although numerically, patients with GU toxicity (grade ≥2) had higher intermediate doses to the bladder (V20 Gy and Dmean) and larger volumes exposed to higher doses in the trigone (V40 Gy, V39 Gy, and V38 Gy). CONCLUSIONS: The trigone exhibits little volume change, but considerable interfractional displacement/deformation. As a result, the relative volume of the trigone receiving high doses during prostate SBRT varies substantially between fractions, which could influence GU toxicity and may not be predicted by radiation planning dosimetry.

Daytime food restriction alters liver glycogen, triacylglycerols, and cell size. A histochemical, morphometric, and ultrastructural study.

BACKGROUND: Temporal restriction of food availability entrains circadian behavioral and physiological rhythms in mammals by resetting peripheral oscillators. This entrainment underlies the activity of a timing system, different from the suprachiasmatic nuclei (SCN), known as the food entrainable oscillator (FEO). So far, the precise anatomical location of the FEO is unknown. The expression of this oscillator is associated with an enhanced arousal prior to the food presentation that is called food anticipatory activity (FAA). We have focused on the study of the role played by the liver as a probable component of the FEO. The aim of this work was to identify metabolic and structural adaptations in the liver during the expression of the FEO, as revealed by histochemical assessment of hepatic glycogen and triacylglycerol contents, morphometry, and ultrastructure in rats under restricted feeding schedules (RFS). RESULTS: RFS promoted a decrease in the liver/body weight ratio prior to food access, a reduction of hepatic water content, an increase in cross-sectional area of the hepatocytes, a moderate reduction in glycogen content, and a striking decrease in triacylglyceride levels. Although these adaptation effects were also observed when the animal displayed FAA, they were reversed upon feeding. Mitochondria observed by electron microscopy showed a notorious opacity in the hepatocytes from rats during FAA (11:00 h). Twenty four hour fasting rats did not show any of the modifications observed in the animals expressing the FEO. CONCLUSIONS: Our results demonstrate that FEO expression is associated with modified liver handling of glycogen and triacylglycerides accompanied by morphometric and ultrastructural adaptations in the hepatocytes. Because the cellular changes detected in the liver cannot be attributed to a simple alternation between feeding and fasting conditions, they also strengthen the notion that RFS promotes a rheostatic adjustment in liver physiology during FEO expression.

Effect of gonadectomy on the metabolism of arachidonic acid in isolated kidney of a rat model of metabolic syndrome.

Influence of sex on arachidonic acid metabolism, a pathway involved in the link between metabolic syndrome (MS) and renal damage, was studied in isolated perfused kidney. Metabolic syndrome was induced by feeding 30% sucrose solution for 24 weeks to intact and gonadectomized female (Ovx) and male (Cas) rats. Systolic blood pressure, albuminuria, as well as prostaglandin E(2) and thromboxane B(2) from urine and perfusate increased in MS male and MS ovariectomized females; castration reduced them in MS males. Perfusion of arachidonic acid in kidneys from MS males increased perfusion pressure compared with controls. No difference appeared in perfusion pressure between control and MS females. Castration diminished perfusion pressure in MS; the opposite was observed in Ovx MS. Perfusion with arachidonic acid plus indomethacin decreased perfusion pressure in MS male kidneys and in Cas MS. In Ovx MS, arachidonic acid plus indomethacin decreased perfusion pressure, but not in female control, MS, and Ovx control. Increase in perfusion pressure with arachidonic acid in both male MS and Ovx MS was related to cyclooxygenase (COX)-1 and COX-2 overexpression in kidney. Castration reduced the expression of COX-1 and COX-2 in MS to control levels. The results suggest that the alteration in arachidonic acid metabolism associated with changes in the expression of COX-1 and COX-2 induced by sucrose intake, and influenced by sex hormones, may contribute to renal damage.

[Cardiac involvement in Kearns-Sayre syndrome]. / Afección cardíaca en el síndrome de Kearns-Sayre.

The mitochondrial cytopathies or oxidative-phosphorylation diseases are a diverse group of disorders that result from the structural, biochemical, or genetic derangement of mitochondria. Because mitochondrial dysfunction can affect the most highly energy-dependent organs, cardiac involvement is frequent in these diseases. To identify the clinical features of Kearns-Sayre syndrome, an entity associated with this group of diseases, we evaluated cardiac structure and function in 5 patients with Kearns-Sayre syndrome and followed the clinical course of these patients for 5 years.

Afección cardíaca en el síndrome de Kearns-Sayre / Cardiac involvement in Kearns-Sayre syndrome

Las citopatías mitocondriales o enfermedades de las fosforilación oxidativa constituyen un diverso grupo de enfermedades cuya etiología subyace en trastornos estructurales, bioquímicos o genéticos de la mitocondria. Dado que una disfunción mitocondrial afecta a los órganos con mayores requerimientos energéticos, la afección cardíaca es frecuente en estos trastornos. Con el fin de determinar las características clínicas de la involucración cardíaca en el síndrome de Kearns-Sayre, entidad asociada a este grupo de enfermedades, hemos estudiado la estructura y la función cardíacas en una serie de 5 casos que, además, han sido seguidos durante 5 años

The mitochondrial cytopathies or oxidative-phosphorylation diseases are a diverse group of disorders that result from the structural, biochemical, or genetic derangement of mitochondria. Because mitochondrial dysfunction can affect the most highly energy-dependent organs, cardiac involvement is frequent in these diseases. To identify the clinical features of Kearns-Sayre syndrome, an entity associated with this group of diseases, we evaluated cardiac structure and function in 5 patients with Kearns-Sayre syndrome and followed the clinical course of these patients for 5 years