Severe Allergy as a Chronic Inflammatory Condition From a Systems Biology Perspective.

Persistent and unresolved inflammation is a common underlying factor observed in several and seemingly unrelated human diseases, including cardiovascular and neurodegenerative diseases. Particularly, in atopic conditions, acute inflammatory responses such as those triggered by insect venom, food or drug allergies possess also a life-threatening potential. However, respiratory allergies predominantly exhibit late immune responses associated with chronic inflammation, that can eventually progress into a severe phenotype displaying similar features as those observed in other chronic inflammatory diseases, as is the case of uncontrolled severe asthma. This review aims to explore the different facets and systems involved in chronic allergic inflammation, including processes such as tissue remodelling and immune cell dysregulation, as well as genetic, metabolic and microbiota alterations, which are common to other inflammatory conditions. Our goal here was to deepen on the understanding of an entangled disease as is chronic allergic inflammation and expose potential avenues for the development of better diagnostic and intervention strategies.

Human red blood cell polymorphisms prevalent in Colombian population and its protective role against malaria.

The populations infected with malaria have developed genetic defense mechanisms in order to protect themselves against the most serious complications of this disease. Those mechanisms have been associated from the perspective of co-adaptive process with some genetic diseases widely present in humans as sickle-cell disease, sickle cell trait and glucose-6-phosphate dehydrogenase deficiency (G6PD). Biochemically, polymorphic mutations at the erythrocyte level have been widely studied, however there is no clear statement of the mechanisms used for resistance against the causative agent of malaria. The purpose of this review is to introduce the molecular and biochemical basis of defense mechanisms associated with two of those adaptations: sickle-cell trait and Glucose-6-phosphate Dehydrogenase Deficiency (G6PD). The first one is a hemoglobinopathy while the second one is the most frequent enzymopathy present in humans.

Attitudes of general dental practitioners in Europe to the microbial risk associated with dental unit water systems.

UNLABELLED: Dental Unit Water Systems (DUWS) are used in dental practices to provide water for cooling of dental equipment and irrigation of the oral cavity. However, they have been demonstrated to be contaminated with micro-organisms. There are currently no European Union (EU) Commission guidelines for the microbial quality of water discharged by DUWS. This study was part of an EU research programme to investigate the microbial contamination of DUWS in general dental practice (GDP) in the UK, Denmark, Germany, The Netherlands, Ireland, Greece and Spain. OBJECTIVE: To undertake a questionnaire survey on the type of DUWS in use and determine the attitude of GDPs to the risk of microbial infection from DUWS. MATERIALS AND METHODS: The questionnaire was written and translated into the language of each country before being posted to each participating dentist. Dentists were asked to complete the questionnaire survey and return it by post. RESULTS AND CONCLUSIONS: The major findings were that the majority of dentists did not clean, disinfect or determine the microbial load of their DUWS, and that dentists would welcome regular monitoring and advice on maintaining their DUWS; the introduction of guidelines; and recommendations on controlling the microbial load of DUWS.

Microangiopathy in kidney and simultaneous pancreas/kidney recipients treated with tacrolimus: evidence of endothelin and cytokine involvement.

BACKGROUND: In the past 3 years, three transplant recipients [one kidney, two simultaneous pancreas/kidney (SPK)] developed a thrombotic thrombocytopenic purpura-like clinical syndrome. This was characterized by an abrupt fall in the hematocrit and platelet count with evidence of hemolysis (fragmented red blood cells and schistocytes) and transplant kidney dysfunction during the first 2 weeks after transplantation. This was also associated with pancreatic dysfunction in the two SPK recipients. In all three patients, elevated tacrolimus levels (>24 ng/ml) occurred. METHODS: Serum cytokine and endothelin levels were determined retrospectively from stored (-70 degrees C) sera. RESULTS: In each case tacrolimus was discontinued, and treatment with plasmapheresis, fresh frozen plasma, steroids, and OKT3 was begun. The clinical courses varied from mild (one patient), to moderate (one patient), to severe (one patient), complicated with seizures and coma. Each patient responded clinically and ultimately was converted to cyclosporine A, and/or mycophenolate mofetil. These clinical events were associated with a rise in serum levels of endothelin and several cytokines. Levels of endothelin were elevated at 209+/-137 pg/ml, particularly in the severe episode where peak levels reached 480 pg/ml (normal 0-20 pg/ml). Peak levels of IL-8 (104+/-36 pg/ml), interleukin- (IL) 10 (238+/-105 pg/ml), and/or IL-12 (306+/-119 pg(ml) mean+/-SE, occurred during or before the clinical event. Serum levels of tumor necrosis factor-a and interferon-gamma were elevated in 2 patients while levels of IL-2, IL-4, and IL-6 were not elevated during the acute phase. CONCLUSIONS: These data are consistent with a mechanism of microangiopathy involving endothelial cell injury (associated with tacrolimus treatment), and accompanied by cytokines (IL-10, IL-12, tumor necrosis factor-a, interferon-gamma) that affect expression of adhesion molecules, chemokines (IL-8) that direct the influx of white blood cells and endothelins that may exacerbate underlying hypertension and increase shear force-related red blood cell destruction.

During development, 17alpha-estradiol is a potent estrogen and carcinogen.

Neonatal administration of estradiol-17beta (E2-17beta) increases the nuclear DNA content in the mouse reproductive tract. Similar responses have been demonstrated for synthetic estrogens such as diethylstilbestrol. One of the questions raised regarding environmental estrogens such as organochlorines is whether they are potent enough to result in abnormal changes such as those demonstrated by both natural and synthetic estrogens. To test this hypothesis, female BALB/c mice were treated neonatally (days 1-5) with either E2-17beta or estradiol-17alpha (E2-17alpha), an inactive stereoisomer in adult reproductive tissues. We also proposed whether neonatal administration of (E2-17alpha) was tumorigenic and whether the effects were age dependent. To answer these questions, one set each of 10 day-old treated and control mice received short-term secondary administration of E2-17beta, E2-17alpha, or cholesterol. Cervicovaginal tracts from intact BALB/c mice were examined histologically and by flow cytometry at 70 days of age and by histology alone at 18 to 22 months of age. The results include several important findings: a) like E2-17beta, neonatal E2-17alpha treatment induced persistent vaginal cornification, hypospadias, vaginal concretions, and hyperproliferation in nearly 100% of the animals regardless of the secondary treatment for most groups; b) neonatal E2-17alpha treatment increased the nuclear DNA content of cervicovaginal epithelium at one-half both the level (mean DNA index of 1.02 vs 1.04) and incidence (22 vs 46% of the animals) of E2-17beta; c) short-term secondary treatment with E2-17alpha, unlike E2-17beta, did not significantly augment the increase in DNA content (13% for E2-17alpha vs 37 and 56% for control and E2-17beta, respectively); and d) neonatal administration with E2-17alpha induced adenosquamous tumors in the reproductive tract in 25% of the animals. Therefore, the biological effects (estrogenic potency) of E2-17alpha may be age dependent.

Conservation of phage reference materials and water samples containing bacteriophages of enteric bacteria.

The survival was determined in different conservation conditions of: somatic coliphages, F-specific RNA bacteriophages and phages infecting Bacteroides fragilis proposed as model micro-organisms for water quality control. Titres of phages of all groups either in pure culture phage suspensions or in naturally occurring phage suspensions were stable at (-70+/-10) degrees C and at (-20+/-5) degrees C when protected with glycerol. Moreover, phage analysis of stored suspensions demonstrated that their numbers were homogeneous, both between vials and within vials, and consequently they can be used as reference materials. Furthermore, changes in the storage temperature of the vials cause unpredictable changes in the numbers of bacteriophages. Consequently, phage reference materials and samples containing a quantitative number of phages must be maintained and dispatched at a constant temperature. Consequently, the results indicate that bacteriophages should be packed in dry ice during transport and storage. Finally, the number of phages in water samples stored at (5+/-3) degrees C in the dark does not decrease significantly during the first 72 h of storage. In addition, phage concentrates from natural samples obtained by adsorption-elution to cellulose nitrate filters and mixed with 10% glycerol were stable at least for 2 months at (-70+/-10) degrees C and at (-20+/-5) degrees C.

Antioxidant properties of dipyridamole as assessed by chemiluminescence.

The ability of dipyridamole (DIP) to scavenge oxygen metabolites generated by either activated human neutrophils (PMNs) or cell-free systems using luminol(s)- and lucigenin-enhanced chemiluminescence was investigated. In the presence of DIP (15-50 microM) a dose-dependent inhibition period was seen in phorbol myristate acetate (PMA)-stimulated PMNs as assayed by isoluminol-enhanced chemiluminescence (ILCL) with horseradish peroxidase (HRP). Although such a lag period was not observed in the absence of HRP, 50 microM DIP inhibited extracellular ILCL by more than 50%. Intracellular luminol-enhanced chemiluminescence (LCL) as assayed in either PMA- or in ionomycin-activated PMNs was not affected by dipyridamole (15-50 microM). In cell-free systems, DIP produced concentration-dependent inhibition in H2O2-(45% at 50 microM), OH- (40%, at 0.1 microM) and HOCl-(20% at 10 microM). Both absorbance and fluorescence scans revealed that DIP is able to react with equimolar quantities of either H202 or HOCl. These results suggest that DIP scavenges reactive oxygen species (ROS) presumably secreted by activated human PMNs in the following decreasing order: *OH > HOCl > H2O2 >> O2-.

Optimisation of the ISO-method on enumeration of somatic coliphages (draft ISO 10705-2).

As part of the EU project "Bacteriophages in Bathing Waters" (January 1996-June 1999) research was carried out to optimise the method for detection and enumeration of somatic coliphages in water as described in ISO/CD 10705-2 of August 1995. It was concluded that this draft ISO standard needed to be amended in certain aspects. For determining the viable count of the host culture WG5 Escherichia coli, a membrane filtration technique should be used instead of spread plate technique as the latter gives lower and less reproducible results. A freshly prepared inoculum culture of host strain WG5 should be used instead of a frozen inoculum culture as freezing of the inoculum culture is found to negatively influence the phage counts. The double agar layer method (DAL) is preferred to the single agar layer method (SAL) for performing the phage analysis as the DAL method gives higher phage counts than the SAL method.

Conocimiento y actitud frente a exposición solar del personal de salud en Atención Primaria, comuna Recoleta, Santiago, Chile / Knowledge and attitude regardings sun exposure in the workers from primary health care, district of Recoleta, Santiago, Chile

Skin cancer rates have increased worldwide despite the current prevention measures. It’s crucial to evaluate people’s knowledge, attitudes, and behaviour regarding sun exposure. Objective: To assess the knowledge and attitudes regarding sun exposure in the workers from primary health care. Method: 223 workers from three Family Care Centres(CESFAM) and from one Primary Emergency Service (SAPU) in the district of Recoleta were surveyed between the months of October and November 2015. Fisher’s exact test and Chi square test were used for statistic analysis. The survey included questions about demographic variables, knowledge of the association between sun radiation/skin cancer and attitudes towards sun protection. Results: the sample consists of 74 men and 149 women, with a mean age of 37 years ±SD 7.9. Phototype III was the most common (41.3percent). The majority of the surveyed declared to be aware of the association between sun exposure and skin cancer (93.3percent). As photoprotecting measures, sunscreens (87.4percent) and seeking shade (71.3percent) were the most frequently measures used. Regarding sunburns, 91.9percent declared to have at least one during their lifetime, 21.5percent occurring during the previous summer. As to the use of sunscreen, 42.1percent referred only using while at the pool / beach and 12.6percent declared not to use it at all. As for health promotion, 29.1percent declared they never recommend the use of sun protection measures in their working practice. Discussion: Although there is adequate knowledge regarding the effects of sun exposure, it doesn’t always reflect on favourable attitudes and photoprotecting measures. There was a significantly greater amount of females with adequate knowledge and use of sun protection measures. This study is one of the first to assess photoprotection behaviour in health care workers.

Síndrome de Buschke-Ollendorf: reporte de un caso y revisión de la literatura / Buschke-Ollendorf syndrome: a case report and literature review

El Síndrome de Buschke-Ollendorf es una rara entidad, descrita por primera vez en 1928. Se caracteriza por la asociación de nevos del tejido conjuntivo y osteopoiquilia. Es una patología de origen multifactorial. Causas genéticas han sido descritas. Dado que es una enfermedad benigna y que no se ha demostrado asociación con otras patologías, no requiere tratamiento y tiene buen pronóstico. Su importancia radica en el diagnóstico diferencial respecto de otras patologías complejas y severas. Se presenta el caso de una niña de 8 años de edad, que presenta desde los 2 años lesiones papulares en región glútea y zona lumbar izquierda, cuyo estudio histológico evidencia nevos de tejido conectivo. Presenta estudio radiológico que muestra la presencia de imágenes sugerentes de osteopoiquilia en fémur y cadera. La asociación de ambas entidades clínicas configura el diagnóstico de Síndrome de Buschke-Ollendorf. Se presenta el caso clínico y revisión de la literatura.

The Buschke-Ollendorf syndrome is a rare entity, first described in 1928 and is characterized by the association of connective tissue nevi and osteopoikilosis. It´s a disease of multifactorial origin. Genetic causes have been described. Since it is a benign disease and no association with other diseases have been proved, it doesn´t require treatment and has a good prognosis. It´s importance lies in the differential diagnosis with other complex and severe pathologies. We present the case of an 8-year-old girl with long lasting papular lesions in left buttock and lower back, which histological study showed connective tissue nevi. The radiological study showed suggestive images of osteopoikilosis in femur and hip. The association of both clinical entities suggest the diagnose of Buschke-Ollendorf syndrome. Clinical case and review of the literature is presented.

Comparison of the efficacies of disinfectants to control microbial contamination in dental unit water systems in general dental practices across the European Union.

Water delivered by dental unit water systems (DUWS) in general dental practices can harbor high numbers of bacteria, including opportunistic pathogens. Biofilms on tubing within DUWS provide a reservoir for microorganisms and should be controlled. This study compared disinfection products for their ability to meet the American Dental Association's guideline of <200 CFU x ml(-1) for DUWS water. Alpron, BioBlue, Dentosept, Oxygenal, Sanosil, Sterilex Ultra, and Ster4Spray were tested in DUWS (n = 134) in Denmark, Germany, Greece, Ireland, The Netherlands, Spain, and the United Kingdom. Weekly water samples were tested for total viable counts (TVCs) on yeast extract agar, and, where possible, the effects of products on established biofilm (TVCs) were measured. A 4- to 5-week baseline measurement period was followed by 6 to 8 weeks of disinfection (intermittent or continuous product application). DUWS water TVCs before disinfection ranged from 0 to 5.41 log CFU x ml(-1). Disinfectants achieved reductions in the median water TVC ranging from 0.69 (Ster4Spray) to 3.11 (Dentosept) log CFU x ml(-1), although occasional high values (up to 4.88 log CFU x ml(-1)) occurred with all products. Before treatment, 64% of all baseline samples exceeded American Dental Association guidelines, compared to only 17% following commencement of treatment; where tested, biofilm TVCs were reduced to below detectable levels. The antimicrobial efficacies of products varied (e.g., 91% of water samples from DUWS treated with Dentosept or Oxygenal met American Dental Association guidelines, compared to 60% of those treated with Ster4Spray). Overall, the continuously applied products performed better than those applied intermittently. The most effective products were Dentosept and Oxygenal, although Dentosept gave the most consistent and sustained antimicrobial effect over time.

Cytogenetics of the parthenogenetic grasshopper Warramaba virgo and its bisexual relatives. VIII. Karyotypes and C-banding patterns in the clones of W. virgo.

Eleven cytological clones of the parthenogenetic grasshopper Warramaba virgo are defined in this paper on the basis of their karyotypes and the C-banding patterns of their chromosomes. These clones are additional to the 16 clones previously described. Seven of the new clones have the standard karyotype and differ only in minor features of the C-bands, the result of amplification or diminution of heterochromatic segments. The remaining 4 clones carry translocations. Of the total of 27 clones of W. virgo now known, 9 carry translocations or fusions. The X + A chromosome is involved in five of these rearrangements and the 1(169) chromosome in four, suggesting a marked nonrandomness with regard to involvement in rearrangements. All the clones with translocations or fusions are known from single localities, suggesting that they are short-lived and do not spread far from their point of origin. A clone that apparently carries a paracentric inversion in one chromosome is more widespread. Clonal diversity in W. virgo seems to be maximal in the Kalgoorlie region of Western Australia, where W. virgo is believed to have arisen, on two separate occasions, by hybridization between two bisexual species. A classification of the clones on the basis of their C-banding patterns is tentatively proposed.

Some neurochemical studies on auditory regions of mouse brain.

The mouse brain auditory pathway has been dissected into five regions: geniculate bodies, posterior colliculi, superior olives, cochlear nuclei, and cochleas. The following analyses were made in these regions and in the auditory cortex: protein, glutamate, gamma-aminobutyrate, taurine, choline acetyltransferase, and glutamate decarboxylase. Taurine levels (nmol . mg of protein-) were highest in cortex (93) and geniculate bodies (60) and lowest in the cochlear nuclei (27) and cochleas (29). Concentrations of gamma-aminobutyrate (same units) were highest in the geniculate bodies (28), low in the superior olives and cochlear nuclei (9 to 10), and undetectable in the cochleas. The distribution of glutamate decarboxylase activity reflected that of gamma-aminobutyrate. The activities of choline acetyltransferase (nmol . of acetylcholine synthesized . h . -1 mg of protein-1) were highest in the superior olives (60) and low in the cochleas (3). These results are interpreted as biocyemical support for previous physiological and pharmacological identification of the olivo-cochlear bundle as cholinergic and the cochlear-nucleus neurones as non-cholinergic. The results also provide further evidence for a role of GABA in the posterior colliculi, but not in the cochleas.

Variation within and between nucleolar organizer regions in Australian hylid frogs (Anura) shown by 18S + 28S in-situ hybridization.

Five distinct classes of secondary constriction are found in the hylid frogs from the genera Litoria and Cyclorana, each of which is defined by its C-banding pattern and morphology (King, 1980, 1987). In-situ hybridization experiments utilizing 18S + 28S copy RNA probes derived from Xenopus and Drosophila rDNA templates, were made on nine species of frogs possessing the major constriction types. Types 1, 2, 4, and 5 are confirmed as being NORs. These results also indicate that type 1 and 2 constriction types are not differentially despiralized as previously suggested, but show absolute differences in the quantity of ribosomal DNA present. This variation took two forms, deletion polymorphism and amplification polymorphism. These differences were observed between homologues within cells and between cells within individuals. Animals possessing these 'despiralized' constrictions are therefore mosaics for both deletion and amplification polymorphisms. Polymorphism frequencies vary greatly between constriction types. Some specimens have a higher level of presence/absence heterozygosity, (L. moorei, type 2, L. nannotis type 5, L. raniformis (animal A, pair 8 type 2), than do others (L. peronii, L. rothii, L. caerulea). The above species also vary markedly in the degree and frequency of amplification of the NORs. The type 4 constrictions analysed (L. coplandi, L. lesueuri and C. novaehollandiae) have a particularly low frequency of presence/absence heterozygosity, and they have fewer size heteromorphisms between homologues. The type 3 ephemeral constrictions did not hybridize to cRNA probes at any stage. In all but one of the species studied, a single pair of chromosomes possessed an NOR. However, in L. raniformis these occurred on two pairs of chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Ribosomal RNA-encoding DNA introgression across a narrow hybrid zone between two subspecies of grasshopper.

A ribosomal RNA-encoding DNA (rDNA) cloned sequence, consisting of a 0.8-kilobase fragment from the 26S/nontranscribed spacer region, was used to identify diagnostic restriction enzyme fragments that distinguish the Moreton and Torresian subspecies of the grasshopper Caledia captiva. These restriction fragments were then used to study patterns of rDNA variation across a narrow geographical hybrid zone between the two subspecies. The pattern of rDNA variation that emerged after the analysis of over 250 individuals clearly demonstrates the asymmetrical introgression of the Moreton ribosomal RNA genes into the Torresian subspecies. This asymmetric movement of genetic material occurs even though there exists extreme postmating F(2) and backcross inviability between the two subspecies. From our data, as well as those of previous chromosomal and allozymic studies, we are able to support the occurrence of nonrandom processes such as biased gene conversion and/or natural selection. Because the rDNA loci in the Moreton and Torresian individuals are located in different regions on chromosomes 10 and 11, it should be possible to determine the relative contributions of conversion, natural selection, and these sorts of processes to the pattern of introgression of the Moreton rDNA into the Torresian subspecies.