Wolcott-Rallison syndrome

Familial hypocholesterolemia, namely abetalipoproteinemia, hypobetalipoproteinemia and chylomicron retention disease (CRD), are rare genetic diseases that cause malnutrition, failure to thrive, growth failure and vitamin E deficiency, as well as other complications. Recently, the gene implicated in CRD was identified. The diagnosis is often delayed because symptoms are nonspecific. Treatment and follow-up remain poorly defined. The aim of this paper is to provide guidelines for the diagnosis, treatment and follow-up of children with CRD based on a literature overview and two pediatric centers 'experience. The diagnosis is based on a history of chronic diarrhea with fat malabsorption and abnormal lipid profile. Upper endoscopy and histology reveal fat-laden enterocytes whereas vitamin E deficiency is invariably present. Creatine kinase (CK) is usually elevated and hepatic steatosis is common. Genotyping identifies the Sar1b gene mutation. Treatment should be aimed at preventing potential complications. Vomiting, diarrhea and abdominal distension improve on a low-long chain fat diet. Failure to thrive is one of the most common initial clinical findings. Neurological and ophthalmologic complications in CRD are less severe than in other types of familial hypocholesterolemia. However, the vitamin E deficiency status plays a pivotal role in preventing neurological complications. Essential fatty acid (EFA) deficiency is especially severe early in life. Recently, increased CK levels and cardiomyopathy have been described in addition to muscular manifestations. Poor mineralization and delayed bone maturation do occur. A moderate degree of macrovesicular steatosis is common, but no cases of steatohepatitis cirrhosis. Besides a low-long chain fat diet made up uniquely of polyunsaturated fatty acids, treatment includes fat-soluble vitamin supplements and large amounts of vitamin E. Despite fat malabsorption and the absence of postprandial chylomicrons, the oral route can prevent neurological complications even though serum levels of vitamin E remain chronically low. Dietary counseling is needed not only to monitor fat intake and improve symptoms, but also to maintain sufficient caloric and EFA intake. Despite a better understanding of the pathogenesis of CRD, the diagnosis and management of the disease remain a challenge for clinicians. The clinical guidelines proposed will helpfully lead to an earlier diagnosis and the prevention of complications.     

Reappraisal of two of Witham's species of fossil wood with taxonomical and nomenclatural notes on Planoxylon Stopes, Protocedroxylon Gothan and Xenoxylon Gothan

Fossil wood collections at the Natural History Museum, London, were searched for the type material of two important species, described as early as 1831 by Witham, on the basis of material at least partly furnished by Nicol and collected in the Liassic of Whitby (Yorkshire, UK). The names given to these two species by Witham are the basionyms for more than ten other species names, while these species names also provide syntypes for several generic names. Despite this, the original material has been only rarely and partly revised, leading to much confusion.We managed to locate some of the original material. Several topotypes were also studied. On the basis of this review we propose here a neotypification for Peuce huttoniana Witham, a lectotypification for Cupressinoxylon barberi Seward and a lectotypification for Tiloxylon Hartig. We evidence several taxonomical and nomenclatural synonymies, assign Peuce lindleyana Witham to Protocedroxylon and P. huttoniana to Xenoxylon Gothan, and introduce the new combination Xenoxylon huttonianum (Witham) nov. comb. as the correct name for Xenoxylon ellipticum Gottwald & Holleis ex Schultze-Motel.A topotype of Araucariopitys americana Hollick & Jeffrey was also reviewed, which, together with previous results, leads us to suggest that Araucariopitys Hollick & Jeffrey, Protocedroxylon Gothan and Planoxylon Stopes should not be considered as taxonomical synonyms. This point is crucial to the interpretation of the fossil record of Early Abietinae.     

Inhibition of phospholipase C disrupts cytoskeletal organization and gravitropic growth in Arabidopsis roots

The phospholipase protein superfamily plays an important role in hormonal signalling and cellular responses to environmental stimuli. There is also growing evidence for interactions between phospholipases and the cytoskeleton. In this report we used a pharmacological approach to investigate whether inhibiting a member of the phospholipase superfamily, phospholipase C (PLC), affects microtubules and actin microfilaments as well as root growth and morphology of Arabidopsis thaliana seedlings. Inhibiting PLC activity using the aminosteroid U73122 significantly inhibited root elongation and disrupted root morphology in a concentration-dependent manner, with the response being saturated at 5 μM, whereas the inactive analogue U73343 was ineffective. The primary root appeared to lose growth directionality accompanied by root waving and formation of curls. Immunolabelling of roots exposed to increasingly higher U73122 concentrations revealed that the normal transverse arrays of cortical microtubules in the elongation zone became progressively more disorganized or depolymerized, with the disorganization appearing within 1 h of incubation. Likewise, actin microfilament arrays also were disrupted. Inhibiting PLC using an alternative inhibitor, neomycin, caused similar disruptions to both cytoskeletal organization and root morphology. In seedlings gravistimulated by rotating the culture plates by 90°, both U73122 and neomycin disrupted the normal gravitropic growth of roots and etiolated hypocotyls. The effects of PLC inhibitors are therefore consistent with the notion that, as with phospholipases A and D, PLC likewise interacts with the cytoskeleton, alters growth morphology, and is involved in gravitropism.     

Spondylodiscitis and an aortic aneurysm due to Campylobacter coli

The aim of the current study was to evaluate the prevalence of stump infections after major amputations of the lower extremities. Patients rehospitalized in Hospital de Base of the Medicine School in São José do Rio Preto in the period from January 2005 to January 2007 due to stump infection after major amputations of lower extremities were evaluated in a retrospective study. All the patients underwent prophylactic antibiotic therapy at the time of the surgery. The Fisher exact test was utilized for statistical analysis with an alpha error of 5% (p-value < 0.05) being considered acceptable. A total of 231 patients were submitted to major amputations during this period and 17 (7.3%) were rehospitalized due to amputation stump infections of which 5 (29.4%) died within one month. The association between death due to stump infection and other causes of death during rehospitalizations was not significant (Fisher exact test: p < 0.1). However, death during rehospitalizations was significantly higher than in the initial hospitalization.     

Neuroprotective properties of levosimendan in an in vitro model of traumatic brain injury

Background  

We investigated the neuroprotective properties of levosimendan, a novel inodilator, in an in vitro model of traumatic brain injury.     

Apremilast,a novel PDE4 inhibitor,inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis

Introduction  

Type 4 phosphodiesterases (PDE4) play an important role in immune cells through the hydrolysis of the second messenger, cAMP. Inhibition of PDE4 has previously been shown to suppress immune and inflammatory responses, demonstrating PDE4 to be a valid therapeutic target for immune-mediated pathologies. We assessed the anti-inflammatory effects of a novel PDE4 inhibitor, apremilast, in human synovial cells from rheumatoid arthritis (RA) patients, as well as two murine models of arthritis.     

First Aegean International Conference on Molecular Recognition

This meeting report describes some of the highlights of the First Biennial Aegean International Conference on Molecular Recognition that took place in Hersonissos, Crete, Greece, between 6 and 11 June 2010. The conference comprised four sessions devoted to: dynamic and combinatorial molecular recognition; B-cell epitope prediction, synthesis and vaccines; nanotechnology approaches to molecular recognition; and host-pathogen interactions. A total of 35 oral communications and 15 posters were presented. The second Aegean International Conference on Molecular Recognition is scheduled to take place in the spring of 2012.     

Primary cilia bend LKB1 and mTOR to their will

Primary cilia are cell surface organelles that act as sensory antennae for various input signals. In a recent issue of Nature Cell Biology, Boehlke et?al. (2010) demonstrate that bending of cilia regulates cell size through a signaling pathway involving the LKB1 and mTOR kinases.