Urinary metabolomics in Fxr-null mice reveals activated adaptive metabolic pathways upon bile acid challenge

Farnesoid X receptor (FXR) is a nuclear receptor that regulates genes involved in synthesis, metabolism, and transport of bile acids and thus plays a major role in maintaining bile acid homeostasis. In this study, metabolomic responses were investigated in urine of wild-type and Fxr-null mice fed cholic acid, an FXR ligand, using ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS). Multivariate data analysis between wild-type and Fxr-null mice on a cholic acid diet revealed that the most increased ions were metabolites of p-cresol (4-methylphenol), corticosterone, and cholic acid in Fxr-null mice. The structural identities of the above metabolites were confirmed by chemical synthesis and by comparing retention time (RT) and/or tandem mass fragmentation patterns of the urinary metabolites with the authentic standards. Tauro-3alpha,6,7alpha,12alpha-tetrol (3alpha,6,7alpha,12alpha-tetrahydroxy-5beta-cholestan-26-oyltaurine), one of the most increased metabolites in Fxr-null mice on a CA diet, is a marker for efficient hydroxylation of toxic bile acids possibly through induction of Cyp3a11. A cholestatic model induced by lithocholic acid revealed that enhanced expression of Cyp3a11 is the major defense mechanism to detoxify cholestatic bile acids in Fxr-null mice. These results will be useful for identification of biomarkers for cholestasis and for determination of adaptive molecular mechanisms in cholestasis.

[Body-packer ; body-stuffer - a medical challenge]

Since the seventies, the practice of drug smuggling in the form of body packing has increased in the Western world. The goal of our study was to present an algorithm for the safe management of intracorporal drug transport based on clinical experience and current evidence. The retrospective study, conducted over the past four years in our hospital prison, analyzes and discusses the diagnostic and therapeutic concepts. Thirty-four patients hospitalized 37 times in a 48-month period were included. In 28 patients drug packages were identified. Only two patients suffered from serious complications. The study demonstrates that following a specifically designed management algorithm based on clinical experience and principles of evidence-based medicine can optimize risk management, improve quality assurance and patient safety.

Neck treatment and shoulder morbidity: Still a challenge

Shoulder complaints and functional impairment are common sequelae of neck dissection. This is often attributed to injury of the spinal accessory nerve by dissection or direct trauma. Nevertheless, shoulder morbidity may also occur in cases in which the spinal accessory nerve has been preserved. In this article, the physiology and pathophysiology of the shoulder are discussed, followed by a consideration of the impact of neck dissection on shoulder complaints, functional impairment, and quality of life. Finally, rehabilitation will be considered. © 2010 Wiley Periodicals, Inc. Head Neck, 2010.

Patient preference for surgical method of abdominal aortic aneurysm repair: postal survey

To determine whether men with small abdominal aortic aneurysm have a preference between either endovascular or open aneurysm repair for future treatment.

Preference for formulations containing calcium and vitamin D(3) in childhood: a randomized-sequence, open-label trial

Children who experience adverse reactions to cow's milk or who have diseases predisposing them to low bone mass are often prescribed a supplementation of calcium and vitamin D(3), but adherence can be poor. Age-specific preferences for different formulations may exist and at least partially explain poor compliance.

"Drug mules" as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

PURPOSE: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox(®)) in the detection of internal cocaine containers. METHODS: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16-45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT=35, nDR=70, nLSDR=30. An overall calculation of all "drug mules" and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. RESULTS: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. CONCLUSIONS: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.

No evidence for a genetic association between female mating preference and male secondary sexual trait in a Lake Victoria cichlid fish

Sexual selection by female mating preference for male nuptial coloration has been suggested as a driving force in the rapid speciation of Lake Victoria cichlid fish. This process could have been facilitated or accelerated by genetic associations between female preference loci and male coloration loci. Preferences, as well as coloration, are heritable traits and are probably determined by more than one gene. However, little is known about potential genetic associations between these traits. In turbid water, we found a population that is variable in male nuptial coloration from blue to yellow to red. Males at the extreme ends of the phenotype distribution resemble a reproductively isolated species pair in clear water that has diverged into one species with blue-grey mates and one species with bright red males. Females of the turbid water population vary in mating preference coinciding with the male phenotype distribution. For the current study, these females were mated to blue males. We measured the coloration of the sires and male offspring. Parents-offspring regression showed that the sires did not affect male offspring coloration, which confirms earlier findings that the blue species breeds true. In contrast, male offspring coloration was determined by the identity of the dams, which suggests that there is heritable variation in male color genes between females. However, we found that mating preferences of the dams were not correlated with male offspring coloration. Thus, there is no evidence for strong genetic linkage between mating preference and the preferred trait in this population [Current Zoology 56 (1): 57-64 2010].

Malignant pheochromocytomas and paragangliomas: a diagnostic challenge

Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare disorders arising from the adrenal gland, from the glomera along parasympathetic nerves or from paraganglia along the sympathetic trunk. According to the WHO classification, malignancy of PCCs and PGLs is defined by the presence of metastases at non-chromaffin sites distant from that of the primary tumor and not by local invasion. The overall prognosis of metastasized PCCs/PGLs is poor. Surgery offers currently the only change of cure. Preferably, the discrimination between malignant and benign PCCs/PGLs should be made preoperatively.