Is the ISAC 112 Microarray Useful in the Diagnosis of Pollinosis in Spain?

BACKGROUND: Multiple sensitization is frequent among pollen-allergic patients. The goal of this study was to determine the diagnostic accuracy of the ImmunoCAP ISAC 112 (ISAC112) microarray in allergy to pollen from several taxa and its clinical utility in a Spanish population. METHODS: Specific IgE was determined in 390 pollen-allergic patients using the ISAC112 microarray. Diagnostic accuracy (sensitivity, specificity, predictive values, and area under the ROC curve) was calculated for the diagnosis of allergy to pollen from grass (n=49), cypress (n=75), olive tree (n=33), plane tree (n=63), and pellitory of the wall (n=17) and compared with that of the singleplex ImmunoCAP immunoassay. RESULTS: The sensitivity of the ISAC112 microarray ranged from 68.2% for allergy to plane tree pollen to 93.9% for allergy to grass pollen. The specificity was >90%. The AUC for the diagnosis of allergy to plane tree pollen was 0.798, whereas the AUC for the remaining cases was ≥0.876. The accuracy of ISAC112 was higher than that of ImmunoCAP for plane tree pollen and similar for the remaining pollens. The frequency of sensitization to most species-specific allergenic components and profilins varied between the different geographical regions studied. A total of 73% of pollen-allergic patients were sensitized to species-specific components of more than 1 pollen type. CONCLUSIONS: The ISAC112 microarray is an accurate tool for the diagnosis of allergy to pollen from grass, cypress, olive tree, plane tree, and pellitory of the wall. The features of the ISAC112 microarray are similar or superior (in the case of plane tree pollen) to those of ImmunoCAP. This microarray is particularly useful for the etiologic diagnosis of pollinosis in patients sensitized to multiple pollen species whose pollination periods overlap.

Adverse reactions to immunotherapy are associated with different patterns of sensitization to grass allergens.

The aim of the study was to investigate whether adverse drug reactions (ADRs) during immunotherapy with a grass extract (AVANZ® Phleum, ALK-Abelló) are related to the different patterns of sensitization of patients to grass allergens. A total of 192 patients with rhinitis and/or asthma sensitized to grass pollen received a 4-week updosing with five injections. ADRs were evaluated following EAACI guidelines. A total of 432 ADRs in 133 (69%) patients were recorded, 64% local and 31% systemic. There was a significant association between the number of grass allergens that sensitized the patients and the total number of ADRs (P = 0.004) occurred locally (P = 0.003) and systemically (P = 0.01). Sensitization to Phl p1 + Phl p5 or Phl p1 + Phl p5 + Phl p12 was significantly associated with a higher frequency of local or systemic reactions (P = 0.001, both). Different patterns of sensitization to grass allergens may potentially be considered a risk marker to the development of ADRs to immunotherapy.

Late-onset systemic lupus erythematosus in Northwestern Spain: differences with early-onset systemic lupus erythematosus and literature review.

To further investigate into the epidaemiology of systemic lupus erythematosus (SLE) in Southern Europe, we have assessed the incidence, clinical spectrum and survival of patients diagnosed with late-onset SLE (age ≥ 50 years) according to the 1982 American College of Rheumatology (ACR) classification criteria at the single hospital for a well-defined population of Lugo, Northwestern (NW) Spain. Between January 1987 and December 2006, 51 (39.3%) of the 150 patients diagnosed as having SLE fulfilled definitions for late-onset SLE. The predominance of women among late-onset SLE (4:1) was reduced when compared with that observed in early-onset SLE (7:1). However, the incidence of late-onset SLE was significantly higher in women (4.2 [95% confidence interval (CI): 3.1-5.6] per 100,000 population) than in men (1.3 [95% CI: 0.6-2.2] per 100,000 population) (p < 0.001). As observed in early-onset SLE, the most frequent clinical manifestation in patients with late-onset SLE was arthritis (71.2%). Renal disease was less common in late-onset SLE (13.5%) than in early-onset SLE (26.4%); p = 0.07). In contrast, secondary Sjögren syndrome was more commonly found in the older age-group (27.1% versus 12.1%; p = 0.03). A non-significantly increased incidence of serositis was also observed in late-onset SLE patients (33.9% versus 22.0%; p = 0.13). Hypocomplementaemia (72.9% versus 91.2%) and positive results for anti-DNA and anti-Sm (49.2% and 6.8% versus 68.1% and 23.1, respectively) were significantly less common in late-onset SLE patients than in early-onset SLE. The probability of survival was reduced in late-onset SLE (p < 0.001). With respect to this, the 10-year and 15-year survival probability were 74.9 % and 63.3% in the late-onset SLE group and 96.3% and 91.0% in patients with early-onset SLE, respectively. In conclusion, our results confirm that in NW Spain SLE is not uncommon in individuals 50 years and older. In keeping with earlier studies, late-onset SLE patients from NW Spain have some clinical and laboratory differences with respect to those individuals with early-onset SLE. Our data support the claim of a reduced probability of survival in the older age-group of SLE patients.

Photocatalysis for continuous air purification in wastewater treatment plants: from lab to reality.

The photocatalytic efficiency of TiO(2)-SiMgO(x) plates to oxidize H(2)S was first evaluated in a flat laboratory reactor with 50 mL min(-1) synthetic air containing 100 ppm H(2)S in the presence of humidity. The use of the photocatalyst-adsorbent hybrid material enhanced the photocatalytic activity in terms of pollutant conversion, selectivity, and catalyst lifetime compared to previous H(2)S tests with pure TiO(2) because total H(2)S elimination was maintained for more than 30 operating hours with SO(2) appearing in the outlet as reaction product only after 18 h. Subsequently, the hybrid material was successfully tested in a photoreactor prototype to treat real polluted air in a wastewater treatment plant. For this purpose, a new tubular photocatalytic reactor that may use solar radiation in combination with artificial radiation was designed; the lamp was turned on when solar UV-A irradiance was below 20 W m(-2), which was observed to be the minimum value to ensure 100% conversion. The efficient distribution of the opaque photocatalyst inside the tubular reactor was achieved by using especially designed star-shaped structures. These structures were employed for the arrangement of groups of eight TiO(2)-SiMgO(x) plates in easy-to-handle channelled units obtaining an adequate flow regime without shading. The prototype continuously removed during one month and under real conditions the H(2)S contained in a 1 L min(-1) air current with a variable inlet concentration in the range of tens of ppmv without release of SO(2).

Tyrosine-194 of glycogenin undergoes autocatalytic glucosylation but is not essential for catalytic function and activity.

Glycogenin is the protein primer for glycogen synthesis. By autocatalytic transglucosylation from UDPglucose, it creates a malto-octaose chain attached to its Tyr-194. It has been uncertain whether the autocatalysis includes the addition of the first glucose residue to Tyr-194. We now show this to be the case. However, we also demonstrate, contrary to a claim by others, that Tyr-194 is not necessary for the catalytic function and activity of glycogenin.

Properties of carbohydrate-free recombinant glycogenin expressed in an Escherichia coli mutant lacking UDP-glucose pyrophosphorylase activity.

Glycogenin, the self-glucosylating primer for glycogen synthesis, is expressed in wild-type E. coli as a recombinant protein in an already partly glucosylated form, owing to the presence of its substrate, UDP-glucose. By using an E. coli mutant strain lacking in UDP-glucose pyrophosphorylase activity, we have succeeded in expressing carbohydrate-free glycogenin (apo-glycogenin) in good yield. When provided with UDPxylose, it autocatalytically adds 1 xylose residue. With UDP-glucose, an average of 8 glucose residues are added. However, release of the self-synthesized maltosaccharide chains with isoamylase reveals them to be a mixture. Chains as long as 11 glucose residues (maltoundecaose) are present. The ability of recombinant apo-glycogenin to self-glucosylate is further proof that a separate enzyme is not needed for the addition of the first glucose residue to Tyr-194 of the protein.

New and specific nucleoside diphosphate glucose substrates for glycogenin.

Glycogenin, the autocatalytic, self-glucosylating primer for glycogen synthesis by glycogen synthase, is presumed, in vivo, to use UDP-glucose as the source of the glucose residues it adds to itself. When we tested its ability to utilize other nucleoside diphosphate glucoses, it emerged that purine nucleotides are not utilized but two pyrimidine nucleotides are used, in addition to UDP-glucose. These are CDP-glucose and TDP-glucose. CDP-glucose is utilized at 70% of the rate of UDP-glucose. While there is no evidence that CDP-glucose is a natural substrate for glycogenin, it has the advantage over UDP-glucose in that it can be used specifically to detect and assay glycogenin in the presence of glycogen synthase because CDP-glucose, unlike UDP-glucose, is not a substrate for the synthase.

Tolerance of a cluster schedule on the treatment of seasonal allergic respiratory disease with pollen extracts quantified in mass units.

In order to evaluate the tolerance of a cluster schedule on specific immunotherapy (SIT), 306 patients were included in a multicenter study. The patients were suffering from rhinoconjunctivitis with/without asthma, caused by sensitization to olive and/or grass pollen. SIT was administered subcutaneously according to a cluster schedule in which the maintenance dose is reached after four visits (3 weeks). The extracts were biologically standardized with major allergens quantified in mass units. Local reactions appeared in 7.2% of the patients and 1.3% of the doses. Systemic reactions (SR) were recorded in 1.2% of the doses administered to 9.5% of the patients. No anaphylactic shock was registered, and all the SR responded fully and rapidly to treatment. There was no difference in SR according to diagnosis or allergen extract used. The majority of SR occurred with the administration of vial of higher concentration (Vial 2: 7 SR (22%), Vial 3: 32 SR (78%), p < 0.05). Of the 32 SR recorded with Vial 3, 13 (41%) were immediate, with no existing association between dose administered and appearance of SR. However, of the 18 delayed SR (56%), 14 occurred after the administration of the first two doses of Vial 3 and four occurred after administration of the second two doses (78% vs 22%, p < 0.05). On the other hand, this regime realized an important saving in cost and time compared to the conventional schedule (1581 fewer doses and 2754 fewer visits were necessary to reach the optimal dose). Considering all these factors, the clinical profile of the proposed regime may be qualified as good. However, future studies are necessary in order to better adjust the schedule to avoid the delayed SR that occurred after the administration of the first two doses of Vial 3.

[Polyarteritis nodosa in a woman with temporal arteritis]. / Poliarteritis nodosa en mujer con arteritis temporal.

A case of a 74-year-old woman, with a histological diagnosis of Transient Arteritis two years before and Nodose Polyarteritis, is described. Although the coexistance of these two vasculitis in a same patient has been rarely described in the literature, we considered that the diagnostic suscpiction of Nodose Polyarteritis should be maintained in a patient with Transient Arteritis developing multisystemic signs.

[Seronegative systemic lupus erythematosus and autoimmune thyroiditis]. / Lupus eritematoso sistémico seronegativo y tiroiditis autoimmune.

The association of systemic lupus erythematosus (SLE) and autoimmune thyroiditis has been previously described. We report a woman with negative antinuclear antibodies (ANA) and criteria for the diagnosis of SLE. The patient was also diagnosed with autoimmune thyroiditis. We review the clinical characteristics and the association of both entities. We also remark in this case the association of autoimmune thyroiditis with seronegative SLE.

[Common variable immunodeficiency and polyarthritis: a case report]. / Inmunodeficiencia común variable y poliartritis: descripción de un caso.

We describe a man with common variable immunodeficiency and polyarthritis. He had suffered several infections, including septic arthritis. For this reason we commenced treatment with antibiotics without obtaining a good response. Three weeks' later, and after knowing that the results of all the cultures were negative, we discontinued the antibiotic therapy and started treatment with indomethacin. A dramatic response was rapidly observed. We feel that an arthritis in a patient with a history of previous infections should alert us to the diagnostic possibility of primary antibody deficiency.

[Comparative study of von Willebrand factor in patients with temporal arteritis]. / Estudio comparativo de factor von Willebrand en pacientes con arteritis de la temporal.

Giant cell arteritis, temporal arteritis (TA), is a vasculitis which affects large and medium-sized vessels. The von Willebrand factor (vWF) is synthesized by endothelial cells and megakaryocytes. Increased amounts of vWF are released into plasma in response to an endothelial damage. vWF levels were studied by Electro-Immunodiffusion in 16 patients with TA (8 of them with a positive biopsy) and their values were compared with 5 patients with Polymyalgia Rheumatica (PMR) and 32 controls. We found higher amount of vWF in global TA, biopsy-positive TA, biopsy-negative TA, and PMR than in controls. There were no relationship between vWF amounts in plasma and clinical findings nor the laboratory parameters. We feel that although in our study vWF might be of some help as an alternative to the biopsy in those patients with high suspicion of TA, the results of other authors raise doubt about the usefulness of the determination of vWF in TA.

Development of a versatile experimental setup for the evaluation of the photocatalytic properties of construction materials under realistic outdoor conditions.

The interest on outdoor photocatalytic materials is growing in the last years. Nevertheless, most of the experimental devices designed for the assessment of their performance operate at controlled laboratory conditions, i.e., pollutant concentration, temperature, UV irradiation, and water vapor contents, far from those of real outdoor environments. The aim of the present study was the design and development of an experimental device for the continuous test of photocatalytic outdoor materials under sun irradiation using real outdoor air as feed, with the concomitant fluctuation of pollutant concentration, temperature, and water vapor content. A three-port measurement system based on two UV-transparent chambers was designed and built. A test chamber contained the photoactive element and a reference chamber to place the substrate without the photoactive element were employed. The third sampling point, placed outdoors, allowed the characterization of the surrounding air, which feeds the test chambers. Temperature, relative humidity (RH), and UV-A irradiance were monitored at each sampling point with specific sensors. NO x concentration was measured by a chemiluminescence NO x analyzer. Three automatic valves allowed the consecutive analysis of the concentration at the three points at fixed time intervals. The reliability of the analytical system was demonstrated by comparing the NO x concentration data with those obtained at the nearest weather station to the experimental device location. The use of a chamber-based reaction system leads to an attenuation of NO x and atmospheric parameter profiles, but maintaining the general trends. The air characterization results showed the wide operating window under which the photoactive materials should work outdoors, depending on the traffic intensity and the season, which are reproduced inside the test chambers. The designed system allows the measurement of the photoactivity of outdoor materials or the comparison of several samples at the same time. The suitability of the system for the evaluation of the DeNO x properties of construction elements at realistic outdoor conditions was demonstrated. The designed experimental device can be used 24/7 for testing materials under real fluctuations of NO x concentration, temperature, UV irradiation, and relative humidity and the presence of other outdoor air pollutants such as VOCs, SO x , or NH3. The chamber-based design allows comparing a photocatalytic material with respect to a reference substrate without the photoactive phase, or even the comparison of several outdoor elements at the same time.

Antioxidant pathways in Alzheimer's disease: possibilities of intervention.

Alzheimer's disease (AD) is closely related to the occurrence of oxidative stress. It was claimed that all pathophysiological mechanisms involved in the onset and progression of AD are related to oxidative stress. Thus, it is important to evaluate if there is oxidative stress as well as the mechanism by which this happens in AD patients as well as in animal models of AD. Extracellular plaques of amyloid b peptides (Aß), a hallmark of the disease, have been postulated to be more protective than damaging in terms of oxidative stress because they may be chemical sinks in which heavy metals are placed. More than a decade ago we reasoned that damage due to Ab might be caused not by extracellular, but rather intracellular Ab peptide interacting with normal cell metabolism. Ab binds to mitochondrial membranes, interacts with heme and thus interferes with the normal electron flow through the respiratory chain. This results in a faulty mitochondrial energy metabolism and in an increased production of reactive oxygen species (ROS). The low mitochondrial energy metabolism may important to explain the hypo metabolism observed in AD patients in vivo (measured by positron emission tomography) and in isolated neurons incubated in the presence of Ab peptide. The increased ROS production results in oxidative stress. The occurrence of such stress provides the basis for a putative treatment of AD with antioxidants. Major efforts have been made to determine whether antioxidant supplementation could be a means of preventing, or even treating AD, but this idea is far from being well- established. We found that even though there is oxidative stress in AD, the administration of antioxidant vitamins, particularly vitamin E, is not effective in preventing the progression of the disease in all patients. We termed this the vitamin E paradox in AD. The paradox is the fact that for some patients, vitamin E could even be detrimental whereas for others vitamin E treatment partially prevents the loss memory associated with the progression of the disease. It is clear, however, that increasing the intake of fruits and vegetables rich in antioxidant vitamins, prevents or retards the onset of AD. Thus, the issue of whether antioxidant treatment is of use in AD is not settled and more research is warranted to clarify this point.

Revisiting the hydrothermal synthesis of titanate nanotubes: new insights on the key factors affecting the morphology.

Recently, titanate nanotubes have attracted a significant deal of interest, but the mechanism of formation as well as some structural aspects of these materials is still under debate. In this context, the main goal of the present study is to identify the key factors affecting the morphology of the titanate nanostructures during hydrothermal synthesis in order to increase the homogeneity and control, as finely as possible, the dimensions of the nanotubes. Previous studies also analyzed the influence of synthesis conditions but, unlike other works, the simultaneous assessment of the influence of parameters such as the phase and crystal size of the TiO(2) used as precursor, and the time and temperature of the hydrothermal treatment has been now analyzed under the same experimental context. The characterization of the prepared materials by means of TEM, XRD, N(2) adsorption isotherms and Raman spectroscopy was performed to establish correlations between the structural features and the preparation conditions. In this research, special attention has been paid to study the non-washed materials, which most of the previous studies have excluded from characterization. After hydrothermal treatment amorphous particles with different morphologies are isolated before acidification, which seems to be a crucial stage in controlling nanotube formation. Besides, the obtained data indicate that some characteristics of the nanotubes, such as the degree of conversion, the homogeneity and crystallinity of the structures or the aspect ratio, can be easily selected by adjusting the synthesis parameters.