On the early uses of the word 'gout': novel evidence and a critical assessment of the published literature.

Recognized since antiquity, gout is still a relevant pathology with rising prevalence and incidence. This study aims to assess the reference accuracy in journal articles mentioning the early use of the word 'gout'. Specifically, it investigates whether the term was indeed coined in the 13th century by the Dominican monk Randolphus of Bocking, as widely believed. Several historical sources in their original Latin were consulted to test the hypothesis of literary mentions predating Randolphus of Bocking's description. At the same time, biomedical articles spanning the last two decades were perused using specific keywords in different combinations to determine the accuracy level of references related to the earliest use of the word 'gout'. The results showed that several biomedical publications wrongly ascribed the origin of the word 'gout' to Randolphus of Bocking. Indeed, various texts predate his mention by many years. In particular, gutta, the Latin word used to indicate a host of rheumatological conditions including gout, is recorded as early as the 10th century in a biography dedicated to the martyred nun Saint Wiborada of St. Gall. Written by Swiss monks between AD 960 and 963, this text should be regarded as containing the earliest known adoption of the word. For this reason, scholars should now avoid quoting Randolph of Bocking's description as the first use of the word 'gout' in Western literature.

Diffusion-driven and size-dependent phase changes of gallium oxide nanocrystals in a glassy host.

Phase transformations at the nanoscale represent a challenging field of research, mainly in the case of nanocrystals (NCs) in a solid host, with size-effects and interactions with the matrix. Here we report the study of the structural evolution of γ-Ga2O3 NCs in alkali-germanosilicate glass - a technologically relevant system for its light emission and UV-to-visible conversion - showing an evolution drastically different from the expected transformation of γ-Ga2O3 into ß-Ga2O3. Differential scanning calorimetry registers an irreversible endothermic process at ∼1300 K, well above the exothermic peak of γ-Ga2O3 nano-crystallization (∼960 K) and below the melting temperature (∼1620 K). Transmission electron microscopy and X-ray diffraction data clarify that glass-embedded γ-Ga2O3 NCs transform into LiGa5O8via diffusion-driven kinetics of Li incorporation into NCs. At the endothermic peak, ß-Ga2O3 forms from LiGa5O8 dissociation, following a nucleation-limited kinetics promoted by size-dependent order-disorder change between LiGa5O8 polymorphs. As a result of the changes, modifications of UV-excited NC light emission are registered, with potential interest for applications.

Anti-sRAGE autoimmunity in obesity: downturn after bariatric surgery is independent of previous diabetic status.

AIM: Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients. METHODS: After exclusion based on specific criteria, 150 subjects (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE autoantibodies were measured before bariatric surgery. Sixty-nine patients were followed for up to 1year after gastric bypass, and their levels of sRAGE and anti-sRAGE autoantibodies measured. The control group consisted of healthy blood donors. RESULTS: Compared with controls, baseline levels of sRAGE and anti-sRAGE autoantibodies were significantly higher in all obese patients independently of glucose regulation (P<0.001). At 1year after gastric bypass, sRAGE and anti-sRAGE were decreased (P<0.001). The decrease in anti-sRAGE autoantibodies was correlated with an increase in high-density lipoprotein (HDL; P=0.02). CONCLUSION: Independently of previous diabetic status, morbid obesity increases sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a decrease in both titres. The decrease in anti-sRAGE correlates with an increase in HDL.

Broadband infrared light-emitting patterns in optical glass by laser-induced nanostructuring of NiO-doped alkali-gallium germanosilicates.

In this Letter, we show functionalization of NiO-doped 7.5Li(2)O·2.5Na(2)O·20Ga(2)O(3)·35SiO(2)·35GeO(2) glass by space-selective nanocrystallization via exposure to the focused beam of a pulsed copper vapor laser (510.6 and 578.2 nm) at temperature close to the glass transition point (570°C). Irradiated areas drastically change their color, caused by electronic transitions of Ni(2+) dopant ions, without any alteration of the optical quality. Importantly, irradiated regions acquire broadband infrared luminescence (centered at about 1400 nm and possessing 400 nm effective bandwidth) typical of Ni(2+) ions in crystalline environment, and by positive change of refractive index (more than 10(-3)). Spectroscopic and diffractometric data of the irradiated regions indeed resemble those previously observed in thermally nanocrystallized glass, with Ni(2+) ions embedded in γ-Ga(2)O(3) nanocrystals. The results demonstrate the possibility of laser writing nanocrystallized multifunction patterns in germanosilicate glasses for the fabrication of active integrated devices.

Nickel-assisted growth and selective doping of spinel-like gallium oxide nanocrystals in germano-silicate glasses for infrared broadband light emission.

The target of taking advantage of the near-infrared light-emission properties of nickel ions in crystals for the design of novel broadband optical amplifiers requires the identification of suitable nanostructured glasses able to embed Ni-doped nanocrystals and to preserve the workability of a glass. Here we show that Ni doping of Li(2)O-Na(2)O-Ga(2)O(3)-GeO(2)-SiO(2) glass (with composition 7.5:2.5:20:35:35 and melting temperature 1480 °C, sensibly lower than in Ge-free silicates) enables the selective embedding of nickel ions in thermally grown nanocrystals of spinel-like gallium oxide. The analysis of transmission electron microscopy and x-ray diffraction data as a function of Ni-content (from 0.01 to 1 mol%) indicates that Ni ions promote the nanophase crystallization without affecting nanoparticle size (~6 nm) and concentration (~4 × 10(18) cm(-3)). Importantly, as shown by optical absorption spectra, all nickel ions enter into the nanophase, with a number of ions per nanocrystal that depends on the nanocrystal concentration and ranges from 1 to 10(2). Photoluminescence data indicate that fast non-radiative decay processes become relevant only at mean ion-ion distances shorter than 1.4 nm, which enables the incorporation of a few Ni ions per nanoparticle without too large a worsening of the light-emission efficiency. Indeed, at 0.1 mol% nickel, the room temperature quantum yield is 9%, with an effective bandwidth of 320 nm.

Glycolaldehyde induces fibrinogen post-translational modification, delay in clotting and resistance to enzymatic digestion.

Glycolaldehyde (GA) is a highly reactive aldehyde that can be generated during inflammation and hyperglycemia. It can react with arginine and lysine residues impairing protein function. As inflammation and diabetes present haemostatic dysfunction, we hypothesized that GA could participate in this process. The aim of this study was to investigate if plasma incubated in the presence of GA presents alteration in the coagulation process. We also aimed to evaluate the role of fibrinogen in GA-induced haemostatic dysfunction. For this purpose, plasma and fibrinogen were each incubated separately, either in the presence or absence of 1 mM GA for 8 and 4 h, respectively. After that, plasma coagulation and fibrin polymerization kinetics were recorded, as well as the kinetic of plasma clot digestion and fibrinolysis protein carbonylation was quantified. An SDS-PAGE was run to check the presence of cross-linking between fibrinogen chains. GA induced a delay in plasma coagulation and in fibrin polymerization. Maximum absorbance decreased after GA treatment, indicating the generation of thinner fibers. Fibrin generated after complete coagulation showed resistance to enzymatic digestion, which could be related to the generation of thinner fibers. Protein carbonylation also increased after GA treatment. All parameters could be reversed with AMG (a carbonyl trap) co-treatment. The data presented herein indicate that GA causes post-translational modification of lysine and arginine residues, which are central to many events involving fibrinogen to fibrin conversion, as well as to fibrinolysis. These modifications lead to the generation of persistent clots and may contribute to mortality seen in pathologies such diabetes and sepsis.

Serum-induced macrophage activation is related to the severity of septic shock.

BACKGROUND: It seems that a balance between anti and pro-inflammatory responses must be kept to eliminate the pathogen without inducing inflammatory damage in the host. Thus we determined the relation between macrophage activation and the severity and clinical outcome in septic patients. MATERIAL AND METHODS: This was a prospective study at a tertiary general intensive care unit. Thirty-three patients admitted with sepsis, severe sepsis or septic shock were included. As a control group, healthy volunteers were included matched to septic patients by age and sex. Peritoneal rat macrophages were cultured with 2% serum from healthy volunteers or from septic patients for determination of phagocytic potential or the capacity to produce cytokines. RESULTS: TNF and IL1 secretion by macrophages activated with serum from sepsis and severe sepsis patients was higher than with serum from healthy controls. In addition, proinflammatory cytokines released in vitro from macrophages, but not determined directly in the serum from patients, were lower in non-survivor septic patients when compared to survivors. In contrast, IL-10 secretion by macrophages activated with serum from septic patients was higher in nonsurvivors. In the septic shock group we observed a diminution in the phagocytic index compared to sepsis and severe sepsis groups, and the phagocytic index was higher in sepsis survivors. CONCLUSIONS: Markers of antiinflammation are predominant in more severe types of sepsis suggesting that antiinflammation is related to mortality.

Cutting edge: the Wiskott-Aldrich syndrome protein is required for efficient phagocytosis of apoptotic cells.

Phagocytosis of apoptotic cells by macrophages and dendritic cells is necessary for clearance of proinflammatory debris and for presentation of viral, tumor, and self Ags. While a number of receptors involved in the cognate recognition of apoptotic cells by phagocytes have been identified, the signaling events that result in internalization remain poorly understood. Here we demonstrate that clearance of apoptotic cells is accompanied by recruitment of the Wiskott-Aldrich syndrome (WAS) protein to the phagocytic cup and that it's absence results in delayed phagocytosis both in vitro and in vivo. Therefore, we propose that WAS protein plays an important and nonredundant role in the safe removal of apoptotic cells and that deficiency contributes significantly to the immune dysregulation of WAS. The efficiency of apoptotic cell clearance may be a key determinant in the suppression of tissue inflammation and prevention of autoimmunity.

Wiskott-Aldrich syndrome protein is necessary for efficient IgG-mediated phagocytosis.

Interactions between the Wiskott-Aldrich (WAS) protein (WASp), small GTPases, and the cytoskeletal organizing complex Arp2/3 appear to be critical for the transduction of signals from the cell membrane to the actin cytoskeleton in hematopoietic cells. This study shows that Fcgamma-receptor (FcgammaR)-mediated phagocytosis is impaired in WASp-deficient peripheral blood monocytes, and that in macrophages, formation of the actin cup and local recruitment of tyrosine phosphorylated proteins is markedly attenuated. Results also show that, in normal macrophages, WASp itself is actively recruited to the cup, suggesting that assembly of this specialized cytoskeletal structure is dependent on its expression. (Blood. 2000;95:2943-2946)

The Wiskott-Aldrich syndrome: disordered actin dynamics in haematopoietic cells.

The Wiskott-Aldrich syndrome protein (WASp) is a member of a unique family whose members share similar domain structures and are responsible for the transduction of signals from the cell membrane to the actin cytoskeleton. For WASp, the interactions with Rho family GTPases and the cytoskeletal organising complex Arp2/3 are critical to these functions, which when disturbed translate into abnormalities of haematopoietic cell signaling, polarisation, migration and phagocytosis. This review discusses the evidence for regulation of highly dynamic cytoskeletal structures by WASp and the consequences of disturbed function on some of these processes.

Sequence-specific antibodies against human IgE isoforms induced by an epitope display system.

BACKGROUND: Unlike other immunoglobulin isotypes, the human C epsilon gene generates by alternative splicing two types of secretory and two types of membrane epsilon chains. The two secreted epsilon heavy chains, epsilon(S1) and epsilon(S2), differ only in the sequence of the last eight C-terminal amino acids, being epsilon(S2) six amino acids longer. The two types of membrane isoforms differ in the extracellular membrane proximal domain, with the longer variant, epsilon(mL), containing 52 extra amino acids which are absent in the shorter epsilon(mS) isoform. OBJECTIVES: We wished to produce quality antibody reagents that specifically detect epitopes that are epsilon isoform-specific. STUDY DESIGN: Short sequences of seven or ten amino acids were chosen as target epitopes and expressed as part of the highly immunogenic loops of deletion variants of engineered Flock House Virus capsid protein RNA2. Chimeric proteins were expressed in E. coli, and used to immunize rabbits. Antisera were screened by immunoblotting of purified IgE isoforms expressed by murine transfectomas. RESULTS: Chimeric proteins expressing epsilon isoform-specific epitopes proved to be strong immunogens in vivo and induced highly specific rabbit antisera. Two antisera so obtained recognize specifically the IgE-S2 isoform. A third one recognizes the long membrane variant m(L)IgE and a fourth one detects an epitope specific to m(S)IgE. CONCLUSION: Here we describe a simplified and efficient protocol of immunization which does not require peptide synthesis and conjugation to carrier protein. Our results show that short peptides of unknown immunogenicity, when genetically introduced into the modified Flock House Virus epitope display system, successfully induced IgE isoform-specific polyclonal antisera in rabbits. These are valuable tools to specifically identify secretory and membrane isoforms of human IgE, and the method is potentially applicable to other variant isoforms or mutants of a given protein.

Functional Fc epsilonRI engagement by a second secretory IgE isoform detected in humans.

We have recently reported that besides the most abundant form epsilonS1, there exists another human secretory epsilon H chain isoform, epsilonS2, resulting from alternative splicing in the epsilonCH4 exon. Using a specific antibody targeted to the epsilonS2-specific C-terminal tailpiece, we now show that this second secretory IgE isoform (IgE-S2) is constitutively co-expressed with the classical secretory IgE-S1 by human myeloma cells. The epsilonS2 variant was also detected in tonsils and in the serum of three non-atopic donors, but was absent in the vast majority of sera of both atopic and non-atopic individuals tested, indicating rare serum expression. IgE-S2 is capable of binding to cells expressing Fc epsilonRI, the high-affinity receptor for IgE. Analysis of intracellular tyrosine phosphorylation signal, degranulation, and rate of receptor internalization suggest a quantitatively lower response by IgE-S2 compared to IgE-S1. The modest differences observed do not appear to overall affect the degranulation competency of IgE-S2, but suggest that the unique structure of the epsilonS2 tailpiece can exert an effect on the interaction with the alpha chain of Fc epsilonRI.

Dentin desensitizing effects of Gluma Alternate, Health-Dent Desensitizer and Scotchbond Multi-Purpose.

PURPOSE: To evaluate the effects of topical applications of Gluma Alternate, a Gluma Desensitizer version with reduced glutaraldehyde content, Health-Dent Desensitizer and Scotchbond Multi-Purpose (SMP) on hypersensitive erosion/abrasion lesions. MATERIALS AND METHODS: 55 patients were included in the trial with at least three teeth each presenting severe sensitivity. From a total of 184 teeth, 69 were treated with Gluma Alternate, 58 with Health Dent and 51 treated SMP, serving as a control. Sensitivity was recorded as response to cold air stimulus prior to treatment, immediately after the topical application of the agents, and after 1 week, 1 month and 6 months. RESULTS: Both Gluma Alternate and SMP showed significant reduction in sensitivity between pre- and postoperative pain scores (P < 0.05). The post-treatment sensitivity scores (0 and 1) were no different between 1 week and 6 months. In the Health-Dent group only 10 of the 58 teeth showed sensitivity reduction. For this reason the remaining 48 teeth received a "rescue treatment" with Gluma Desensitizer. At the end of the 6-month observation time, all teeth treated with Gluma Alternate, Gluma Desensitizer, and SMP showed no or very little dentin sensitivity.

Retinal identification in Pelvetia fastigiata.

Unidirectional blue light directs the rhizoid-thallus axis in the apolar zygote of the brown alga Pelvetia fastigiata. This effect is mediated by an increase in the intracellular concentration of cGMP. Here, we show the extraction, purification and identification of 1 microgram of all-trans retinal from 1.2 x 10(6) Pelvetia zygotes. The number of retinal molecules per cell was about 4 x 10(9). Since retinal, wherever present, is exclusively associated with an opsin to form a light sensitive complex (rhodopsin-like proteins), and since the physiological response originated by this protein produces a variation of cGMP concentration, this new finding suggests that a rhodopsin-like protein could be the photoreceptor in this brown alga.

A methylation-dependent DNA-binding activity recognising the methylated promoter region of the mouse Xist gene.

Differential methylation of CpG sites in the promoter region of the mouse Xist gene is correlated with Xist expression and X-chromosome inactivation in the female. Using oligonucleotides encompassing the differentially methylated sites as probes in band-shift assays, we have identified a nuclear protein which binds to a specific region of the promoter (between base pairs -45 and -30 upstream from the transcription start site) only when CpG sites within the CG rich region (GCGCCGCGG, -44 to -36) are methylated. Competition experiments with methylated or unmethylated heterologous oligonucleotides demonstrate that the activity is sequence-specific as well as methylation-dependent. Analysis by Southwestern blot identifies a protein of approximately 100 kDa molecular weight and confirms strong binding to the methylated Xist promoter oligonucleotide. Using a 233bp Xist-promoter luciferase construct in which the cytosines in the three CpG sites in the -44 to -36 region are mutated to thymine, we have established that this region is required for transcription from the mouse Xist promoter. Therefore, we suggest that the binding of the 100kDa protein to the methylated sequence leads to repression of transcription from the methylated Xist allele, thus suggesting a role in the regulation of both imprinted and random Xist transcription and X-chromosome inactivation.

Laboratory evaluation of compomers in Class V restorations.

PURPOSE: To evaluate the in vitro microleakage, marginal morphology and resin tags configuration of a compomer restorative material (Dyract) alternatively used with two different bonding systems (Dyract-PSA and Prime & Bond 2.0). A hybrid resin composite (Prisma TPH) used with two different bonding systems (Universal Bond 3 and ProBond) was evaluated as control material. MATERIALS AND METHODS: Class V non-retentive restorations were made in vitro at CEJ and divided at random in four groups: Dyract/PSA, Dyract/P&B 2.0, Prisma TPH/UB3, and Prisma TPH/ProBond. The latter two groups were as controls. After finishing the restorations, an impression material was used to obtain an epoxy resin replica for SEM analysis of margin alterations. Percentage of perfect margin was evaluated under SEM and calculated comparing it with the width/length of restoration margin. The presence of gaps, enamel fractures and other marginal alterations was also recorded inspecting under SEM replicas. Each tooth was then immersed for 24 hours in erythrosin B dye solution at room temperature and evaluated at superficial margins as marginal leakage (ML) for dye penetration. Each sample was then longitudinally sectioned, and leakage was expressed as % dye penetration of the total cavity wall, longitudinal leakage (LL). Finally, each tooth was dissolved (10%H3PO4 for 48 hours and NaOCl solution for additional 24 hours) to leave only the resin restoration. The internal walls of each restoration were then inspected by SEM at x1,000-15,000 to evaluate the presence of resin-dentin infiltrated layer (hybrid layer) and to calculate the ability of primer/bonding to infiltrate peritubular dentin and to form resin tags. RESULTS: Gap widths were 2-6 microns at dentin and lower at enamel. Several enamel fractures along the margin were observed. Resin tags were observed only in deeper dentin. Only Prime & Bond 2.0/Dyract formed resin tags at medium-superficial dentin. The length of resin tags ranged from 1-6 microns for Dyract-PSA primer to 100 microns for Prime & Bond 2.0. Marginal and longitudinal leakage was observed both at dentin and enamel levels. The best dentin seal was obtained with Prime & Bond 2.0/Dyract, while enamel seals were equivalent with both bonding systems (P > 0.05). No correlations were demonstrated between leakage and SEM observations.

In Vivo Gibberellin Biosynthesis in Endosperm of Sechium edule Sw. Seeds.

Biosynthesis of gibberellins (GAs) was studied in vivo in endosperms of Sechium edule Sw. Exogenous ent-[(14)C]kaurene was metabolized into four major products: GA(12), GA(4), GA(7) and 16, 17-dihydro-16-hydroxy-GA(15) alcohol glucoside. Other minor metabolites were also observed including ent-kaurenol and ent-kaurenal. Conversion of ent-[(14)C]kaurene to ent-kaurenol glucoside by endosperm cell-free preparations in the presence of UDPG was observed. However, the finding was not confirmed in in vivo studies and is probably artifactual. Overall evidence coming from the analysis of endogenous GAs and in vitro and in vivo biosynthetic studies are discussed in relation to the possible existence in the Sechium seeds of a different route, along with the known pathway, branching from ent-kaurene or ent-7-alpha-hydroxykaurenoic acid and this also leading to biologically active GAs.