Feeding efficiency of planktivores under disturbance, the effect of water colour, predation threat and shoal composition.

The consumption of phantom midge Chaoborus flavicans larvae by Perca fluviatilis showed clear response to water colour, predation threat and shoal composition with the most significant negative effect for water colour. In the case of Rutilus rutilus, no similar combined response was observed and the total prey consumption was significantly negatively affected by predation threat of Esox lucius. The results suggest that differences in life-history traits may result in disparity in species-specific responses to disturbance.

Enhanced production of 24S-hydroxycholesterol is not sufficient to drive liver X receptor target genes in vivo.

BACKGROUND: Oxysterols such as 24S-hydroxycholesterol (OHC) and 27-OHC are intermediates of cholesterol excretion pathways. In addition, they are putative endogenous agonists of the liver X receptor (LXR) class of nuclear hormone receptors and are thought to be important mediators of cholesterol-dependent gene regulation. 24S-OHC is one of the most efficient endogenous LXR agonists known and is present in the brain and in the circulation at relatively high levels. OBJECTIVES: To explore the regulatory importance of 24S-OHC in vivo. DESIGN: We developed a transgenic mouse model in which human cholesterol 24-hydroxylase, the enzyme responsible for the formation of 24S-OHC, was expressed under the control of a promoter derived from the ß-actin gene. RESULTS: Both male and female transgenic mice had elevated levels of cerebral, plasma, biliary and faecal 24S-OHC. According to the faecal excretion results, production of 24S-OHC was increased four- to sevenfold. Gene expression profiling revealed that the elevated production of 24S-OHC did not result in the anticipated activation of LXR target genes in the brain or liver. CONCLUSION: In spite of the fact that 24S-OHC is a highly effective agonist of LXRs in vitro, it is not a critical activator of target genes to this nuclear receptor in vivo, either in the brain or in the liver.

Diet shifts and food selection of perch Perca fluviatilis and roach Rutilus rutilus in humic lakes of varying water colour.

The field data from four humic lakes suggested that water colour may have both direct and indirect effects on inter- and intra-specific interactions of perch Perca fluviatilis and roach Rutilus rutilus. The results agree with suggestions that, compared with R. rutilus, P. fluviatilis may be an inferior forager on zooplankton in highly coloured water. As an indirect effect, water colour decreases the coverage of macrophytes and limits suitable littoral habitats, benefiting R. rutilus over P. fluviatilis. Perca fluviatilis benefiting from complex habitats does not have the advantage in macrophyte-poor highly coloured water.

Environmental factors regulate the effects of roach Rutilus rutilus and pike Esox lucius on perch Perca fluviatilis populations in small boreal forest lakes.

In this study of 18 small boreal forest lakes, the effects of abiotic and biotic factors (roach Rutilus rutilus and pike Esox lucius) on various population variables of perch Perca fluviatilis were examined. As a single variable, the gillnet catch per unit effort (CPUE) of R. rutilus was negatively related to the mean mass of small (< 200 mm) and the growth rate of young (1-2 years) P. fluviatilis. The mean mass of large (> or = 200 mm) P. fluviatilis was the highest at intermediate CPUE of R. rutilus. Redundancy analysis including environmental factors and P. fluviatilis population variables suggested that 'predation-productivity-humus' gradient affected P. fluviatilis populations by decreasing the CPUE and mean mass of small individuals but increasing these variables of large individuals. The CPUE of R. rutilus and lake area had a negative effect on small and a positive effect on large P. fluviatilis growth rate. In small boreal forest lakes, P. fluviatilis populations are affected by the partially opposite forces of competition by R. rutilus and predation by E. lucius, and the intensity of these interactions is regulated by several environmental factors.

Genetic depletion of Soat2 diminishes hepatic steatosis via genes regulating de novo lipogenesis and by GLUT2 protein in female mice.

Depletion of the cholesterol esterifying enzyme acyl-Coenzyme A: cholesterol acyltransferase 2 (ACAT2, encoded by Soat2) protects mice from atherosclerosis, diet-induced hypercholesterolemia, and hepatic steatosis when fed high-cholesterol diet. The glucose transporter 2 (GLUT2) represents the main gate of glucose uptake by the liver. Lipid synthesis from glucose (de novo lipogenesis; DNL) plays a pivotal role in the development of hepatic steatosis. Inhibition of DNL is a successful approach to reverse hepatic steatosis, as shown by different studies in mice and humans. Here we aimed to investigate whether depletion of Soat2 per se can reduce hepatic steatosis, also in the presence of very low levels of cholesterol in the diet, and the underlying mechanisms. Female Soat2-/- and wild type mice were either fed high-fat or high-carbohydrate diet and both contained <0.05% (w/w) cholesterol. Analysis in serum, liver, muscles and adipose tissues were performed. We found Soat2-/- mice fed high-fat, low-cholesterol diet to have less hepatic steatosis, decreased expression of genes involved in DNL and lower hepatic GLUT2. Similar findings were found in Soat2-/- mice fed high-carbohydrate, low-cholesterol diet. CONCLUSION: Depletion of Soat2 reduces hepatic steatosis independently of the presence of high levels of cholesterol in the diet. Our study provides a link between hepatic cholesterol esterification, DNL, and GLUT2.

Use of a fluorescently labeled poly-caspase inhibitor for in vivo detection of apoptosis related to vascular-targeting agent arsenic trioxide for cancer therapy.

Arsenic trioxide (ATO, Trisenox) is a potent anti-vascular agent and significantly enhances hyperthermia and radiation response. To understand the mechanism of the anti-tumor effect in vivo we imaged the binding of a fluorescently-labeled poly-caspase inhibitor (FLIVO) in real time before and 3 h or 24 h after injection of 8 mg/kg ATO. FSaII tumors were grown in dorsal skin-fold window chambers or on the rear limb and we observed substantial poly-caspase binding associated with vascular damage induced by ATO treatment at 3 and 24 h after ATO injection. Flow cytometric analysis of cells dissociated from the imaged tumor confirmed cellular uptake and binding of the FLIVO probe. Apoptosis appears to be a major mode of cell death induced by ATO in the tumor and the use of fluorescently tagged caspase inhibitors to assess cell death in live animals appears feasible to monitor and/or confirm anti-tumor effects of therapy.

Contrecoup intracerebellar hemorrhage: report of a case.

A case of contrecoup intracerebellar hematoma is reported. Only one other similar case has been reported in the literature. This complication must be considered in head-injured patients, particularly in the presence of neurological deterioration in association with a cerebellar contusion demonstrated on the initial computed tomographic (CT) scan. Serial CT scanning is particularly important because of delayed intraparenchymal hemorrhage, which in this case occurred in the cerebellum.

Fractures of the sella turcica.

Five recent cases of sella turcica fracture examined at the Medical Center Hospital of Vermont are reported. These fractures are most commonly associated with frontal or maxillofacial trauma and are complicated by cranial nerve palsies, chiasmatic injury, and cerebrospinal fluid rhinorrhea and otorrhea. The mortality rate with these fractures is high because of the associated brain injury. The importance of a detailed endocrine evaluation to detect developing pituitary abnormalities is also emphasized. The accuracy of radiographic diagnosis of these fractures utilizing plain skull films, tomography, and computed axial tomography is reviewed. the importance of cerebral angiography to evaluate the intracavernous internal carotid arteries and the basilar artery is also emphasized, as is the theoretical basis of the pathological findings associated with these fractures.

Cerebellopontine angle gumma.

A rare lesion, a gumma in the cerebellopontine angle, is reported. Gumma may mimic other more commonly occurring cerebellopontine angle tumors. The computed tomographic (CT) appearance and histological characteristics are discussed. The literature of cerebral gumma is reviewed. This is the only reported case of cerebellopontine angle gumma seen on CT scan and verified histologically at operation.

Thrombosed vein of Galen aneurysm.

The authors report a case of thrombosed vein of Galen aneurysm in a 4.5-year-old girl with craniofacial dysostosis (Crouzon's disease). Six previously reported cases appear in the literature. The initial presentation is often associated with the symptoms and signs of hydrocephalus. Computed tomography shows an enhancing mass in the region of the posterior 3rd ventricle with the characteristic "target sign." Arteriography of all aspects of both the anterior and the posterior cerebral circulation is essential. Surgical results in cases of vein of Galen aneurysm have generally been poor, but recent reports of successful operative intervention to treat the thrombosed variety promise satisfactory treatment.

A technique to analyse the kinetics and energetics of cane-assisted gait.

UNLABELLED: The purpose of this study was to develop a biomechanical technique to analyse the kinetics of cane-assisted gait. Biomechanical measures such as ground reaction forces (force platforms), cane reaction forces, and kinematics have been routinely measured. However, a full kinetic analysis of both the lower limb and the cane-assisted limb has not been reported: joint reaction forces, moments of force and mechanical powers. Such estimates give the researcher and clinician insight into the levels at each of the joints and the kinetics of the muscles responsible for the altered locomotion and stability. Standard inverse dynamics techniques were employed using a three-dimensional force transducer in the tip of the cane and as the subject walked over a force platform while his movement was recorded on video. Special problems existed when both the cane and foot bore weight on the force platform; the resultant indeterminacy problem was resolved so that independent solutions could be applied to both the lower and upper limbs. RELEVANCE: A full kinetic and energetic biomechanical analysis is needed to identify motor pattern changes at each joint resulting from the use of the cane. Such information will be useful in pinpointing not only motor pattern changes at an affected joint but also adaptive motor pattern changes at other joints. Also, the contribution of the muscles at the wrist, elbow, and shoulder becomes evident not only to the stability of the gait but also to the energetics of forward propulsion.

Bioanalysis in clinical development of tasquinimod using liquid chromatography/tandem mass spectrometry.

Tasquinimod (ABR-215050) is an oral drug in clinical development for treatment of patients with castrate resistant prostate cancer. This paper describes a method for the determination of tasquinimod in human plasma. The method is based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) using stable isotope labeled tasquinimod as internal standard (IS). The plasma samples were processed by protein precipitation using acidic acetonitrile containing the IS. The precipitated samples were centrifuged and the supernatant was injected directly into the LC-MS/MS system. Chromatographic separation was performed on a reversed phase column using fast gradient elution, with a total run cycle time of 4 min. The method was validated with respect to accuracy, precision, dynamic range, lower limit of quantification, selectivity and robustness. Furthermore, the stability of tasquinimod in spiked plasma, in processed extracts and in incurred samples was thoroughly studied. The method was validated in the range of 1.0-2400 nmol/L, defining the lower and upper limits of quantification. The repeatability, reproducibility and overall bias were 1.5-7.1%, 3.5-7.4%, and 1.3-4.7%, respectively, in the range of 1-2000 nmol/L. Excellent selectivity was demonstrated in the validation, as well as in study samples from both healthy volunteers and cancer patients. Robustness was demonstrated by the calculated carry-over as low as 0.06%, and by an incurred sample reproducibility (ISR) experiment where 97% of the reanalyzed samples fulfilled the acceptance criteria of 20% deviation from initial analysis result. Also, tasquinimod was found to be stable in all investigated matrices, including in incurred samples. In an incurred sample stability (ISS) investigation, tasquinimod was demonstrated to be stable for 24 months, and 97% of the reanalyzed samples were within 20% from the initial analysis result. In conclusion, the method was demonstrated to be accurate, precise, robust and reliable for the determination of tasquinimod. The method was successfully used in several clinical studies for the support of pharmacokinetic and pharmacodynamic evaluations.