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Sensitization
Kinds of Sensitization Terms modified by Sensitization Selected AbstractsDermatitis from common ivy (Hedera helix L. subsp. helix) in Europe: past, present, and futureCONTACT DERMATITIS, Issue 4 2010Evy Paulsen Common ivy (Hedera helix subsp. helix) is a well-known native and ornamental plant in Europe. Reports on contact dermatitis from ivy have regularly appeared since 1899. Recently, it has been suggested that allergic contact dermatitis from the plant may be under-diagnosed, partly due to lack of commercial patch test allergens. The objective of the article is to present the results of aimed patch testing with the main common ivy allergen, falcarinol, during a 16-year period and review the newer literature. Consecutive patients tested with falcarinol 0.03% petrolatum from May 1993 to May 2009 were included. Cases published since 1987 were retrieved from the PubMed database. One hundred and twenty-seven Danish patients were tested with falcarinol and 10 (7.9%) tested positive. Seven were occupationally sensitized. Between 1994 and 2009, 28 new cases of contact dermatitis from ivy were reported, 2 of which were occupational. Only 11 of the 28 patients were tested with pure allergens. Falcarinol is not only widely distributed in the ivy family, but also in the closely related Apiaceae. Sensitization may occur in childhood or in adults pruning ivy plants or handling them in an occupational setting. In view of the ubiquity of falcarinol-containing plants and the relatively high prevalence of positive reactions in aimed patch testing, falcarinol should be the next plant allergen to be commercially available and included in the plant series worldwide. [source] Sensitization to 26 fragrances to be labelled according to current European regulationCONTACT DERMATITIS, Issue 1 2007Results of the IVDK, review of the literature To study the frequency of sensitization to 26 fragrances to be labelled according to current European regulation. During 4 periods of 6 months, from 1 January 2003 to 31 December 2004, 26 fragrances were patch tested additionally to the standard series in a total of 21 325 patients; the number of patients tested with each of the fragrances ranged from 1658 to 4238. Hydroxymethylpentylcyclohexene carboxaldehyde (HMPCC) was tested throughout all periods. The following frequencies of sensitization (rates in %, standardized for sex and age) were observed: tree moss (2.4%), HMPCC (2.3), oak moss (2.0), hydroxycitronellal (1.3), isoeugenol (1.1), cinnamic aldehyde (1.0), farnesol (0.9), cinnamic alcohol (0.6), citral (0.6), citronellol (0.5), geraniol (0.4), eugenol (0.4), coumarin (0.4), lilial (0.3), amyl-cinnamic alcohol (0.3), benzyl cinnamate (0.3), benzyl alcohol (0.3), linalool (0.2), methylheptin carbonate (0.2), amyl-cinnamic aldehyde (0.1), hexyl-cinnamic aldehyde (0.1), limonene (0.1), benzyl salicylate (0.1), ,-methylionon (0.1), benzyl benzoate (0.0), anisyl alcohol (0.0). 1) Substances with higher sensitization frequencies were characterized by a considerable number of ,++/+++' reactions. 2) Substances with low sensitization frequencies were characterized by a high number of doubtful/irritant and a low number of stronger (++/+++) reactions. 3) There are obviously fragrances among the 26 which are, with regard to contact allergy, of great, others of minor, and some of no importance at all. [source] P02 Analysis of coupled patch test reactions to nickel, cobalt and chromateCONTACT DERMATITIS, Issue 3 2004Janice Hegewald Concomitant sensitizations to Nickel, Cobalt and Chromate are often observed among patch test patients. However, the reasons for being sensitized to two or more of these substances are not completely understood. Examination of IVDK (http://www.ivdk.org) patch test results with multivariate procedures has been conducted to further elucidate the mechanisms involved with these sensitizations and potential exposure factors that may have led to the concomitant sensitizations. Gender, age, occupational dermatitis, and construction work were considered and examined with multivariate logistic regression models with the dependent response variable being concurrent reactions to a metal pair versus no reactions. In addition to the aforementioned anamnestic data, examination of a poly-sensitizations variable (reactions to 1, 2, or 3 standard series allergens other than Nickel, Cobalt or Chromate) provided information regarding general susceptibility to positive patch test reactions. Combined reactions to Cobalt and Chromate were strongly linked to construction work (OR = 11.23 (7.46, 16.90)) and occupational dermatitis. Female patch test patients had a higher odds of a positive patch test reaction to both Nickel and Cobalt (OR = 4.73 (3.81, 5.87)). Sensitization to other, unrelated standard series substances was associated with concurrent reactions to all of the metal pairs. The association between construction work and Cobalt-Chromate reactions corresponds with the hypothesis that cement exposures lead to cobalt-chromate sensitizations. Individual susceptibility to delayed-type sensitizations, as represented by the poly-sensitization variable, also appears to be associated with coupled sensitizations to metals and warrants further examination. [source] Dual Luminescent Dinuclear Gold(I) Complexes of Terpyridyl-Functionalized Alkyne Ligands and Their Efficient Sensitization of EuIII and YbIII LuminescenceEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 22 2010Xiu-Ling Li Abstract Reaction of (tpyC6H4C,CAu)n {tpyC6H4C,CH = 4,-(4-ethynylphenyl)-2,2,:6,,2,-terpyridine} with diphosphane ligands Ph2P(CH2)xPPh2 (x = 2 dppe, 3 dppp, 4 dppb, 5 dpppen, 6 dpph) in CH2Cl2 afforded the corresponding dual luminescent binuclear gold(I) complexes [(tpyC6H4C,CAu)2(,-dppe)] (1), [(tpyC6H4C,CAu)2(, - dppp)] (2), [(tpyC6H4C,CAu)2(,-dppb)] (3), [(tpyC6H4C,CAu)2(,-dpppen)] (4), [(tpyC6H4C,CAu)2(,-dpph)] (5). Crystal structural analysis of complexes 1·2CH2Cl2 and 2·2CH2Cl2 show that the terpyridine moieties are free of coordination in these gold(I)-acetylide-phosphane complexes. Spectrophotometric titration between complex 1 and [Eu(tta)3] (Htta = 2-thenoyltrifluoroacetone) or [Yb(hfac)3(H2O)2] (Hhfac = hexafluoroacetylacetone) gave a 2:1 ratio between Ln(,-diketonate)3 (Ln = Eu, Yb) units and the complex 1 moiety, indicating the formation of Au2Ln2 complexes. Both the luminescence titrations and the luminescence quantum yields of Au2Ln2 (Ln = Eu, Yb) solutions show that the energy transfer occurs efficiently from the binuclear gold(I) antennas 1,5 to EuIII and YbIII centers, and all complexes 1,5 are good energy donors for sensitization of visible and NIR luminescence of EuIII and YbIII ions. [source] Synthesis, Characterization, and Photophysical Properties of Some Heterodimetallic Bisporphyrins of Ytterbium and Transition Metals , Enhancement and Lifetime Extension of Yb3+ Emission by Transition-Metal Porphyrin SensitizationEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 21 2007Feng-Lei Jiang Abstract A series of d-f heterodimetallic bisporphyrin complexes (YbZn, YbPd, and YbPt), in which a YbIII porphyrinate moiety is linked to a transition-metal porphyrinate moiety by a flexible three-carbon chain, were synthesized. They were fully characterized by high-resolution mass spectrometry, 1H and 31P NMR spectroscopy, electronic absorption, andfluorescence methods. Variable-temperature near-infrared photoluminescence studies showed that the transition-metal porphyrinate moiety would enhance the ytterbium(III) emission centered at about 998 nm and extend its emission lifetime. YbPd and YbPt showed large two-photon absorption cross-section values because of the interaction between the porphyrin units, which caused a loss of centrosymmetry. Optical limiting investigation demonstrated that [Yb(TPP)(LOMe)] and YbPt have comparable performance to C60 by virtue of their heavy-metal effect. Our results indicate that these bisporphyrin dimetallic complexes will find valuable applications in the field of nonlinear optics. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] A PCP-Pincer RuII,Terpyridine Building Block as a Potential "Antenna Unit" for Intramolecular SensitizationEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 18 2007Marcella Gagliardo Abstract The redox- and photoactive mononuclear complex [Ru(PCP)(tpy,DTTANa4)]Cl {PCP = [C6H3(CH2PPh2)2 -2,6],; tpy,DTTA4, = 4,-(2,2,:6,,2,-terpyridine)-diethylenetriamine- N,N,N,,N, -tetraacetate} possesses an externally directed, vacant N3O4 polyaminocarboxylate-type binding site that coordinates to lanthanide(III) ions to give the neutral heterodinuclear RuII,LnIII complexes [Ru(PCP)(tpy,DTTA)Ln(H2O)2] (Ln = Gd3+, Eu3+). The photophysical properties of solutions of the mononuclear complex [Ru(PCP)(tpy,DTTANa4)]Cl were investigated in MeOH/EtOH (1:4) and compared to those of the solutions of heterodinuclear complexes [Ru(PCP)(tpy,DTTA)Ln(H2O)2] (Ln = Gd3+, Eu3+). Rigid matrix excitation at 77 K of the ,,* level of the ruthenium chromophore in the [Ru(PCP)(tpy,DTTA)Eu(H2O)2] complex results in a weak europium(III) emission pointing to a transfer of energy from Ru,Eu as a result of the metal-to-ligand charge-transfer (MLCT) excited state of the ruthenium component to the luminescent lanthanide ion. The excited state lifetime of the europium complex is 0.2 ms in methanol solution. In deuterated solvents, the lifetime increases to 0.4 ms, which indicates that the process is solvent-dependent as a result of the strongly coordinated molecules of water that are responsible for the quenching in nondeuterated solvents.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Decrease of D2 receptor binding but increase in D2 -stimulated G-protein activation, dopamine transporter binding and behavioural sensitization in brains of mice treated with a chronic escalating dose ,binge' cocaine administration paradigmEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008A. Bailey Abstract Understanding the neurobiology of the transition from initial drug use to excessive drug use has been a challenge in drug addiction. We examined the effect of chronic ,binge' escalating dose cocaine administration, which mimics human compulsive drug use, on behavioural responses and the dopaminergic system of mice and compared it with a chronic steady dose (3 × 15 mg/kg/day) ,binge' cocaine administration paradigm. Male C57BL/6J mice were injected with saline or cocaine in an escalating dose paradigm for 14 days. Locomotor and stereotypy activity were measured and quantitative autoradiographic mapping of D1 and D2 receptors, dopamine transporters and D2 -stimulated [35S]GTP,S binding was performed in the brains of mice treated with this escalating and steady dose paradigm. An initial sensitization to the locomotor effects of cocaine followed by a dose-dependent increase in the duration of the locomotor effect of cocaine was observed in the escalating but not the steady dose paradigm. Sensitization to the stereotypy effect of cocaine and an increase in cocaine-induced stereotypy score was observed from 3 × 20 to 3 × 25 mg/kg/day cocaine. There was a significant decrease in D2 receptor density, but an increase in D2 -stimulated G-protein activity and dopamine transporter density in the striatum of cocaine-treated mice, which was not observed in our steady dose paradigm. Our results document that chronic ,binge' escalating dose cocaine treatment triggers profound behavioural and neurochemical changes in the dopaminergic system, which might underlie the transition from drug use to compulsive drug use associated with addiction, which is a process of escalation. [source] Sensitization of meningeal nociceptors: inhibition by naproxenEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Dan Levy Abstract Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non-selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non-selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single-unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non-selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of A,- and C-units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX-2 inhibitor N -[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) onto the dural receptive field of A,- and C-unit nociceptors also reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache. [source] Plateau potential-dependent windup of the response to primary afferent stimuli in rat dorsal horn neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2000Valérie Morisset Abstract In the spinal cord, repetitive stimulation of nociceptive afferent fibres induces a progressive build-up of dorsal horn neuron (DHN) responses. This ,action potential windup' is used as a cellular model of central sensitization to pain. It partly relies on synaptic plasticity, being reduced after blocking NMDA and neurokinin receptors. Using intracellular recordings in a slice preparation of the rat spinal cord, we have analysed the implication of an additional non-synaptic component of windup. Primary afferent fibres were electrically stimulated in the dorsal root. Of 47 responding deep DHNs, 17 (36%) produced action potential windup and afterdischarge during consecutive periods of repeated stimuli (0.4,1 Hz) activating high- (n = 13 neurons) and low-threshold (n = 6 neurons) afferent fibres. When the NMDA receptors were blocked, the rate of windup did not change. In all neurons, there was an absolute correlation between expression of windup and the production of calcium-dependent plateau potentials. Sensitization of the DHN response, similar to the synaptically induced windup, was obtained by repetitive intracellular injection of depolarizing current pulses. This intracellularly induced windup had the same pharmacology as the plateau potential. Synaptically induced windup was also abolished by nifedipine, an L-type calcium-channel blocker. Expression of plateau properties in DHNs is therefore a critical component of windup, operating downstream of synaptic processes. Being associated with calcium influx, generation of plateau potentials could be a link between short-term plasticity and the long-term modification of DHN excitability associated with central sensitization. [source] Near IR Sensitization of Organic Bulk Heterojunction Solar Cells: Towards Optimization of the Spectral Response of Organic Solar CellsADVANCED FUNCTIONAL MATERIALS, Issue 2 2010Markus Koppe Abstract The spectroscopic response of a poly(3-hexylthiophene)/[6,6]-phenyl-C61 -butyric acid methyl ester (P3HT/PCBM)-based bulk heterojunction solar cell is extended into the near infrared region (NIR) of the spectrum by adding the low bandgap polymer poly[2,6-(4,4-bis-(2-ethylhexyl)-4H -cyclopenta[2,1- b;3,4- b´]-dithiophene)- alt -4,7-(2,1,3-benzothiadiazole)] [PCPDTBT] to the blend. The dominant mechanism behind the enhanced photosensitivity of the ternary blend is found to be a two-step process: first, an ultrafast and efficient photoinduced charge transfer generates positive charges on P3HT and PCPDTBT and a negative charge on PCBM. In a second step, the positive charge on PCPDTBT is transferred to P3HT. Thus, P3HT serves two purposes. On the one hand it is involved in the generation of charge carriers by the photoinduced electron transfer to PCBM, and, on the other hand, it forms the charge transport matrix for the positive carriers transferred from PCPDTBT. Other mechanisms, such as energy transfer or photoinduced charge transfer directly between the two polymers, are found to be absent or negligible. [source] Urea Sensitization Caused by Separation of Helicobacter pylori RNA Polymerase , and ,, SubunitsHELICOBACTER, Issue 2 2007Daiva Dailidiene Abstract Background:, The , and ,, subunits of RNA polymerase are fused in all Helicobacters, but separate in most other taxa. Prior studies had shown that this fusion is not essential for viability in culture or in vivo, but had not tested it for potentially important quantitative effects on phenotype. Methods:, The effect of separating rpoB and rpoC sequences on Helicobacter pylori growth was tested in culture and during mouse infection. Results:, Derivatives of strains X47 and SS1 carrying this "rpoBCsplit" allele colonized mice less vigorously than their wild-type parents in competition tests. With X47 rpoBCsplit, this reduced vigor was evident in wild-type mice, whereas with SS1 rpoBCsplit it was seen only in cytokine IL-10- and IL-12,-deficient mice. In culture, the rpoBCsplit allele sensitized each of four strains tested (X47, SS1, 88-3887, and AM1) to urea, a metabolite that is secreted into the gastric mucosa; urea sensitization was more severe in X47 than in SS1 genetic backgrounds. The rpoBCsplit allele also caused poorer growth on Ham's F12 agar, a nutritionally limiting medium, but had little effect on sensitivity to mild acidity. Conclusions:,H. pylori's normal RNA polymerase ,-,, subunit fusion contributes quantitatively to fitness. We propose that urea, although important to H. pylori in vivo, also be considered inhibitory; and that H. pylori's natural ,-,, subunit fusion helps it cope with urea exposure. [source] Covalent modification as a mechanism for the breakdown of immune tolerance to pyruvate dehydrogenase complex in the mouseHEPATOLOGY, Issue 6 2004Jeremy M. Palmer The autoimmune liver disease primary biliary cirrhosis (PBC) is characterized by the breakdown of normal immune self tolerance to pyruvate dehydrogenase complex (PDC). How tolerance is broken to such a central and highly conserved self antigen in the initiation of autoimmunity remains unclear. One postulated mechanism is that reactivity arises to an altered form of self antigen with subsequent cross-reactivity to native self. In this murine study, we set out to examine whether sensitization with a covalently modified form of self PDC can give rise to the pattern of breakdown of B-cell and T-cell tolerance to self PDC seen in PBC patients. The notion that altered self can lead to tolerance breakdown was studied by sensitizing SJL/J mice with a covalently modified (biotinylated) preparation of self murine PDC (mP/O-B). Subsequently, antibody and T-cell reactivities to unmodified self mP/O were studied. Sensitization with mP/O-B elicited high-titre, high-affinity antibody responses reactive with both the mP/O-B immunogen and, importantly, native mP/O. In addition, significant MHC class II restricted splenic T-cell responses to native mP/O (i.e., true autoimmune responses) were seen in mP/O-B sensitized animals. The breakdown of T-cell self tolerance to mP/O was not seen in animals sensitized with irrelevant biotinylated antigens. In conclusion, this study provides evidence to support the concept that exposure to covalently modified self PDC can, in the correct proimmune environment, replicate the full breakdown of B-cell and T-cell immune tolerance to PDC seen in PBC. One potential etiological pathway in PBC therefore could be the breakdown of tolerance to self PDC occurring after exposure to self antigen covalently modified in the metabolically active environment of the liver. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2004;39:1583,1592.) [source] Bacterial motif DNA as an adjuvant for the breakdown of immune self-tolerance to pyruvate dehydrogenase complexHEPATOLOGY, Issue 3 2002David E. J. Jones Bacterial DNA containing unmethylated CpG dinucleotide motifs is immunostimulatory to mammals, skewing CD4+ T-cell responses toward the Th1 phenotype. Autoreactive T-cell responses seen in primary biliary cirrhosis (PBC) are typically of the Th1 phenotype, raising the possibility that bacterial DNA might play a role in the generation of pathologic autoimmunity. We therefore studied the effects of CpG motif-containing oligodeoxynucleotides (ODN) on responses to pyruvate dehydrogenase complex (PDC, the autoantigen in PBC) in a murine model. Sensitization of SJL/J mice with non,self-PDC has been shown to result in induction of autoreactive T-cell responses to PDC sharing characteristics with those seen in patients with PBC. Administration of CpG ODN to SJL/J mice at the time of sensitization with PDC resulted in a significant skewing of splenic T-cell response to self-PDC, with significant augmentation of the Th1 cytokine response (interleukin [IL] 2 and interferon [IFN] gamma) and reduction of the Th2 response (IL-4 and IL-10). In fact, CpG ODN seemed to be more effective at biasing the response phenotype and as effective at inducing liver histologic change as complete Freund's adjuvant (CFA), the standard adjuvant used for induction of Th1 responses in murine autoimmune and infectious immunity models. In conclusion, our findings raise the possibility that bacteria play a role in the development of autoimmunity (in PBC at least) through the potential of their DNA to shift the T-cell responses toward the phenotype associated with autoimmune damage. Moreover, this study suggests caution in the therapeutic use of CpG ODN as vaccine adjuvants. [source] Food allergy in adolescents and adultsINTERNAL MEDICINE JOURNAL, Issue 7 2009J. Yun Abstract There has been an increase in the prevalence of food allergy in the last few decades. Adult food allergy may represent persistence of reactions that commenced in infancy and early childhood or it may be initiated in adulthood through new sensitizations. Persistence of peanut allergy is an example of the former situation. Approximately 20% of children will develop tolerance to peanuts, so there will be an increasing number of individuals reaching adulthood where this problem will need ongoing management. In addition to peanut, tree nuts, fruits, vegetables and seafood are implicated as common causes of food allergy in adulthood. Sensitization may occur directly to a food allergen or indirectly through cross-reactivity with an aeroallergen. Adults may present with a spectrum of clinical manifestations from oral allergy syndrome to fatal anaphylaxis. The management of food allergy consists of appropriate education regarding avoidance of implicated foods, modifying potential risk factors for anaphylaxis, such as asthma and prompt recognition and treatment of acute reactions. [source] Bacillus Calmette-Guérin-pulsed dendritic cells stimulate natural killer T cells and ,,T cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2007Michio Naoe Background: Immunotherapy with bacillus Calmette-Guérin (BCG) for bladder cancer is successful, although the precise mechanism is unclear. Natural killer (NK) cells are a candidate for BCG-activated killer cells, but the roles of other T lymphocytes, such as NKT cells and ,,T cells, are not fully understood. Mycobacterium tuberculosis is a potent activator of both NKT cells and ,,T cells. However, it is known that the patient's prognosis is good if there are increased numbers of dendritic cells (DCs) in the urine after BCG therapy. Therefore, we investigated whether DCs are matured by BCG and whether BCG-pulsed DCs stimulate NKT cells and ,,T cells. Methods: Naïve Pan T cells were isolated form peripheral blood mononuclear cells (PBMCs) and DCs were obtained by culturing CD14+ monocytes with granulocyte,macrophage colony-stimulating factor and interleukin-4. The DCs were pulsed with BCG and their maturation was measured by fluorescence-activated cell sorter analysis using the CD86 antibody. Naïve T lymphocytes were stimulated by coculture with BCG-pulsed DCs in vitro, followed by FACS analysis to estimate the ratio and activation of NKT cells and the ratio of ,,T cells. The 51Cr (chromium) release assay was used to estimate the cytotoxic activity of the stimulated T cells. Cytolytic proteins in the patient's PBMCs were measured during BCG therapy using semiquantitative reverse transcriptase-polymerase chain reaction. Results: The DCs were matured by BCG stimulation and the number of NKT cells and ,,T cells increased after culturing with BCG-pulsed DCs. The BCG-pulsed DCs also activated the NKT cells and ,,T cells. Also, the lymphocytes that were cocultured with the BCG-pulsed DCs showed unspecific cytotoxic activity against a bladder cancer cell line. Conclusion: Sensitization of NKT cells and ,,T cells by BCG-pulsed DCs might be one of the mechanisms of BCG immunotherapy. [source] Contact allergy and medicinal herbsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2008Werner Aberer Summary Herbal treatments are becoming increasingly popular, and are often used for internal as well as dermatological conditions, both externally as well as orally. The prevalence of contact sensitization against several plants especially of the Compositae family is quite high in Europe. Sensitization seems to occur relatively frequent with a few species such as arnica, elecampane and tea tree (oil), and occurs rarely with the majority. Testing for plant allergy is problematic because of the limited number of commercially available standardized patch test substances and the danger of active sensitization when testing with plants, parts thereof, or individual extracts. Knowledge about the allergic potential of plants is limited. Although plants are regarded as critical allergens by dermatologists, the number of reported cases of contact dermatitis is relatively small.Many widely used substances are not licensed as drugs or cosmet-ics. While the positive effects are frequently questionable or limited, the side effects are often more evident. Adverse effects of herbal medicines are an important albeit neglected subject in dermatology, which deserves further systematic investigation. [source] Nerve growth factor-evoked nociceptor sensitization in pig skin in vivoJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010Roman Rukwied Abstract Peripheral sensitization of skin nociceptors by nerve growth factor (NGF) was explored in pig skin in vivo. As an objective output measure, the area of axon-reflex-mediated erythema was assessed upon mechanical, thermal, chemical, and electrical stimuli delivered at 1, 3, and 7 days after i.d. injection of 1 ,g NGF into the pig's back skin (n = 8). Pretreatment with NGF provoked a sensitization to mechanical (600 mN), thermal (10 sec 49°C) and chemical (15 ,l, pH 3) stimuli that lasted for 7 days. No sensitization, however, was found in response to weak mechanical (100 mN), weak thermal (10 sec 45°C), or electrical stimuli. Irrespective of the skin pretreatment (NGF or PBS vehicle control), the area of electrically induced erythema decreased upon repetition (days 1,7) by 70% (P < 0.05). Sensitization of sensory endings by NGF upon mechanical, heat, and chemical stimuli suggests recruitment of sensory transducer molecules [e.g., TRPV1, acid-sensing ion channels (ASICs)]. In contrast, the gradual decrease in electrically induced erythema over 7 days might be attributable to axonal desensitization and possibly activity-dependent down-regulation of sodium channels. Thus, long-lasting sensitization processes of nociceptor endings or axonal sodium channel desensitization mechanisms can be explored in the pig as a translational experimental animal model. © 2010 Wiley-Liss, Inc. [source] Sensitization of Ventral Tegmental Area Dopamine Neurons to the Stimulating Effects of EthanolALCOHOLISM, Issue 9 2009Zheng-Ming Ding Background:, Previous studies indicated that chronic alcohol drinking increased the sensitivity of the posterior ventral tegmental area (p-VTA) to the reinforcing effects of ethanol. The current study tested the hypothesis that local exposure of the p-VTA to ethanol would increase the sensitivity of dopamine (DA) neurons to the stimulating effects of ethanol. Methods:, Experiment 1 examined the stimulating effects of ethanol in the p-VTA after a 7-day ethanol pretreatment in the p-VTA. Adult female Wistar rats were pretreated with microinjections of 200 mg% ethanol or artificial cerebrospinal fluid (aCSF) into the p-VTA once a day for 7 days. On the eighth day, rats received a challenge injection of ethanol (100, 200, or 300 mg%) or aCSF into the p-VTA, and extracellular DA levels were measured in the nucleus accumbens (NAc) shell with microdialysis. Experiment 2 examined the stimulating effects of ethanol (200 mg%) after a 3- or 5-day ethanol (200 mg%) pretreatment in the p-VTA. Experiment 3 examined the stimulating effects of ethanol (200 mg%) 7 days after the last of the 7-day ethanol (200 mg%) pretreatments in the p-VTA. Results:, Experiment 1: in both aCSF- and ethanol-pretreated rats, the challenge microinjection of ethanol dose-dependently increased DA release in the NAc shell, with significantly greater increases in ethanol-pretreated groups. Experiment 2: the 5-day, but not 3-day, ethanol pretreatment protocol increased the response of p-VTA dopamine neurons to the ethanol challenge. Experiment 3: the increased stimulating effects of ethanol were still evident after 7 days. Conclusions:, The results indicate that repeated local ethanol exposure of the p-VTA produced neuroadaptations in DA neurons projecting to the NAc shell, resulting in a persistent increase in the sensitivity of these neurons to the stimulating effects of ethanol. [source] Electroacupuncture Inhibits Ethanol-Induced Locomotor Sensitization and Alters homer1A mRNA Expression in MiceALCOHOLISM, Issue 8 2009Jair Guilherme Dos Santos Jr Background:, Here we investigated the effects of electroacupuncture over locomotor sensitization induced by ethanol in mice. Methods:, Adult male Swiss mice were daily injected with ethanol (2 g/kg, i.p.) or saline for 21 days (acquisition phase). After 4 days of withdrawal, all animals were challenged with ethanol (1.4 g/kg, i.p.). The locomotor activity during 30 minutes was accessed just after the ethanol challenge. Electroacupuncture at acquisition, expression, or maintenance phases of locomotor sensitization was provided over ST-36 (Zusanli) or PC-6 (Neiguan) as well as concomitantly over these 2 acupoints. One hour after the challenge with ethanol, the animals were decapitated, the hippocampus, striatum, and prefrontal cortex were dissected, and the expression of homer1A mRNA assessed by PCR. Results:, Electroacupuncture provided simultaneously over ST-36 and PC-6 (but not to ST-36 or PC-6 alone) inhibited the acquisition, expression, and maintenance of ethanol-induced locomotor sensitization. In addition, electroacupuncture blocked the diminution of homer1A mRNA expression triggered by ethanol in the acquisition (striatum and prefrontal cortex), expression (hippocampus), and in the maintenance (hippocampus and prefrontal cortex) phases. Conclusion:, Electroacupuncture provided concomitantly over ST-36 and PC-6 prevents the sensitization of the mesocorticolimbic pathway induced by ethanol in mice. In addition, these effects were accompanied by changes in the expression of homer1A. We suggest that electroacupuncture effects over ethanol-induced locomotor sensitization are associated to its ability to modulate homer1A expression and glutamatergic plasticity. [source] Proopiomelanocortin Peptides Are Not Essential for Development of Ethanol-Induced Behavioral SensitizationALCOHOLISM, Issue 7 2009Amanda L. Sharpe Background:, Behavioral sensitization is a result of neuroadaptation to repeated drug administration and is hypothesized to reflect an increased susceptibility to drug abuse. Proopiomelanocortin (POMC) derived peptides including ,-endorphin and ,-melanocyte stimulating hormone have been implicated in development of behavioral sensitization and the reinforcing effects of alcohol and other drugs of abuse. This study used a genetically engineered mouse strain that is deficient for neural POMC to directly determine if any POMC peptides are necessary for the development of ethanol-induced locomotor sensitization. Methods:, Adult female mice deficient for POMC in neurons only (Pomc,/,Tg/Tg, KO) and wildtype (Pomc+/+Tg/Tg, WT) littermates were injected once daily with either saline or ethanol (i.p.) for 12 to 13 days. On ethanol test day (day 13 or 14) all mice from both treatment groups received an i.p. injection of ethanol immediately before a 15-minute analysis of locomotor activity. Blood ethanol concentration (BEC) was measured on ethanol test day immediately following the test session. Baseline locomotor activity was measured for 15 minutes after a saline injection 2 days later in both groups. Results:, There was no significant difference in BEC between genotypes (WT = 2.11 ± 0.06; KO = 2.03 ± 0.08 mg/ml). Both WT and nPOMC-deficient mice treated repeatedly with ethanol demonstrated a significant increase in locomotor activity on test day when compared to repeated saline-treated counterparts. In addition, mice of both genotypes in the repeated saline groups showed a significant locomotor stimulant response to acute ethanol injection. Conclusions:, Central POMC peptides are not required for either the acute locomotor stimulatory effect of ethanol or the development of ethanol-induced locomotor sensitization. While these peptides may modulate other ethanol-associated behaviors, they are not essential for development of behavioral sensitization. [source] Sensitization, Duration, and Pharmacological Blockade of Anxiety-Like Behavior Following Repeated Ethanol Withdrawal in Adolescent and Adult RatsALCOHOLISM, Issue 3 2009Tiffany A. Wills Background:, Repeated ethanol withdrawal sensitizes anxiety-like behavior in adult rats and causes anxiety-like behavior and decreased seizure thresholds in adolescent rats. Current experiments determined if adolescent rats exhibit sensitized anxiety-like behavior, the duration of this effect, if drug pretreatments blocked these effects, and if these effects differed from those seen in adults. Methods:, Male adolescent rats received three 5-day cycles of 2.5% ethanol diet (ED) separated by two 2-day withdrawal periods, continuous 15 days of 2.5%ED, or a single 5-day cycle of 2.5%ED. Male adult rats received three 5-day cycles of either 2.5% or 3.5%ED. These groups were tested 5 hours into the final withdrawal for social interaction (SI) deficits (an index of anxiety-like behavior). Ethanol intake was monitored throughout and blood concentrations were obtained from separate groups of rats. Additionally, adolescent rats were tested for SI 1, 2, 7, 14, and 18 days and adults 1 and 2 days after the final withdrawal. Some adolescent rats were also pretreated with the CRF1 antagonist CP-154,526, the 5-HT1A agonist buspirone, or the benzodiazepine receptor antagonist flumazenil during the first 2 withdrawals. Results:, SI was reduced in adolescent rats following repeated withdrawals of 2.5%ED while neither a continuous or single cycle ED exposure caused this effect. Adult rats also had reduced SI following repeated withdrawals from both 2.5% and 3.5%ED. This effect was present up to 1 week following the final withdrawal in adolescents but returned to baseline by 1 day in adults. CP-154,526, buspirone, or flumazenil prevented this reduction in SI in adolescent rats. Conclusions:, Adolescent rats exhibit sensitized anxiety-like behavior following repeated withdrawals at ED concentrations similar to those used in adults. However, this effect is longer lasting in adolescent rats. Drugs modulating CRF, 5-HT, or GABA systems during initial withdrawals prevent the development of anxiety-like behavior otherwise manifest during a final withdrawal in adolescent rats. [source] Only Male Mice Show Sensitization of Handling-Induced Convulsions Across Repeated Ethanol Withdrawal CyclesALCOHOLISM, Issue 3 2007L.M. Veatch Background: Alcohol abuse, especially when experienced in multiple cycles of chronic abuse and withdrawal, leads to a sensitization of central nervous system hyperexcitability that may culminate in overt expression of seizures. In spite of the growing prevalence of alcohol abuse and dependence in females shown in recent epidemiologic studies, evidence of sexual dimorphism in the expression of alcohol withdrawal-induced seizures and the development of seizure sensitization following multiple cycles of ethanol (EtOH) exposure and withdrawal has not been examined in either animal models or in clinical reports. Methods: Subjects in these experiments were male and female C3H/Hecr mice. The female mice were intact or ovariectomized, with ovariectomized mice receiving 17- , -estradiol or placebo pellets. All mice were exposed to 4 cycles of exposure to 16-hour EtOH vapor, separated by 8-hour withdrawal periods. During each 8-hour withdrawal, hourly assessment of seizure propensity was assessed as handling-induced convulsions. Additional assessments were taken up to 72 hours after the final EtOH withdrawal cycle. Results: Male and female mice showed similar seizure propensity during an initial withdrawal from chronic EtOH. Across subsequent withdrawal cycles, however, male mice exhibited a robust increase in seizure severity beginning with the third withdrawal cycle. In marked contrast, female mice failed to demonstrate sensitization of seizure severity. The lack of seizure sensitization following up to 4 cycles of alcohol exposure and withdrawal could not be explained by hormonal status (presence or absence of estrogen) or by sex differences in blood alcohol levels. Conclusions: Male and female mice exposed to the same number of cycles of EtOH withdrawal demonstrate differences in expression of seizures. Males show the typical sensitization of seizures, or kindling response, which has been reported clinically as well as in animal models, but females do not. The reason for the lack of seizure sensitization in female mice remains to be elucidated, but may be related to sex differences in alcohol effects on excitatory/inhibitory neurotransmission, rather than to hormonal or blood alcohol level differences. [source] Inhibition of Caspases In Vivo Protects the Rat Liver Against Alcohol-Induced Sensitization to Bacterial LipopolysaccharideALCOHOLISM, Issue 6 2001Ion V. Deaciuc Background: The mechanisms of liver sensitization by alcohol to Gram-negative bacterial lipopolysaccharide (LPS) remain elusive. The purpose of this study was two-fold: (1) to test the hypothesis that alcohol-enhanced liver apoptosis may be a sensitizing mechanism for LPS and (2) to further characterize the liver apoptotic response to alcohol. Methods: Rats were fed a high-fat, alcohol-containing liquid diet for 14 weeks, treated with LPS (1.0 mg/kg of body weight, intravenously) or saline, followed by injection of a pan-caspase inhibitor {IDN1965;N -[(1,3-dimethylindole-2-carbonyl)-valinyl]-3-amino-4-oxo-5-fluoropentanoic acid; 10 mg/kg of body weight, intraperitoneally} or vehicle, and killed. The following parameters were assessed: plasma aspartate: 2-oxoglutarate aminotransferase activity (AST); liver histology and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) response; caspase-3, ,8, and ,9 activity; and mRNA and protein expression for two apoptosis-signaling molecules: Fas receptor and Fas ligand; and three apoptosis adaptors: Bax, Bcl-XL, and Bcl-2. Results: Alcohol-feeding-induced liver steatosis, slightly increased caspases' activity, the number of TUNEL-positive nuclei, and facilitated the LPS necrotic effect without affecting mRNA expression of apoptosis signals and adaptors. LPS induced a significant increase in AST and the number of TUNEL-positive nuclei, both effects being more pronounced in alcohol-treated rats. LPS produced hepatic necrosis only in alcohol-treated rats. LPS effects were associated with up-regulation of mRNA expression for both apoptosis adaptors and signaling molecules. IDN1965 administration 3 hr after LPS injection strongly inhibited caspases' activity, particularly that of caspase-3. IDN1965 also abolished the increase in TUNEL-positive nuclei, reversed the effect of LPS on plasma AST in alcohol-treated rats, and prevented LPS-induced necrosis. Conclusions: (1) Alcohol-enhanced liver apoptosis may not involve regulatory steps at the transcriptional level. LPS-induced liver apoptosis seems to involve transcriptional regulation of several apoptosis adaptors. Therefore, alcohol and LPS may enhance liver apoptosis through different mechanisms. (2) Alcohol-enhanced liver apoptosis precedes and may facilitate the hepatic effects of LPS. LPS superimposed on alcohol further elevates the rate of apoptosis in the liver. This may exceed the phagocytosing capacity of the liver so that all the apoptotic cells are not phagocytosed, but rather die of necrosis. [source] A convenient and sensitive allergy test: IgE crosslinking-induced luciferase expression in cultured mast cellsALLERGY, Issue 10 2010R. Nakamura To cite this article: Nakamura R, Uchida Y, Higuchi M, Nakamura R, Tsuge I, Urisu A, Teshima R. A convenient and sensitive allergy test: IgE crosslinking,induced luciferase expression in cultured mast cells. Allergy 2010; 65: 1266,1273. Abstract Background:, For the detection of allergen-specific IgE in sera, solid-phase IgE-binding assays like the CAP test are commonly used. Although such immunochemical methods are very sensitive, they frequently produce false positives. Degranulation of the human IgE receptor (Fc,RI)-transfected rat mast cell (RBL) lines seems to be a possible indicator for human IgE, but spontaneous mediator release from these cells in the presence of human sera is not negligible. Methods:, The nuclear factor of activated T-cells (NFAT)-responsive luciferase reporter gene was stably transfected into human Fc,RI-expressing RBL-SX38 cells. One established clone (RS-ATL8) was sensitized with 1 : 100 dilution of sera from patients with egg white allergy and then stimulated with purified or a crude extract of egg white allergen. Results:, Sensitization with 15 pg/ml IgE was sufficient to detect IgE crosslinking,induced luciferase expression (EXiLE) by anti-IgE stimulation. Allergen-specific EXiLE was elicited by as little as 1 fg/ml of egg white protein without cytotoxicity. There was a good correlation between results with EXiLE and oral food challenge tests on patients with egg allergy (P = 0.001687, Fisher's exact test). The measured values of EXiLE and the CAP test also correlated well (R = 0.9127, Spearman's test). Conclusion:, The EXiLE test using RS-ATL8 cells is a promising in vitro IgE test to evaluate the biological activity of the binding between IgE and allergens. [source] Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysisALLERGY, Issue 9 2010P. Burney To cite this article: Burney P, Summers C, Chinn S, Hooper R, van Ree R, Lidholm J. Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis. Allergy 2010; 65: 1182,1188. Abstract Background:, Reports of adverse reactions to foods are increasing, but there is limited information on the comparative prevalence of sensitization to food allergens using standardized methods. Methods:, Sera from the ,random sample' of young adults seen during the second phase of the European Community Respiratory Health Survey were analysed for IgE against 24 foods using ImmunoCAP. Sera were tested on five food mixes, and subsequently on individual foods in each positive mix. Results:, Sera from 4522 individuals living in 13 countries were tested for at least one food allergen mix. Prevalence of sensitization to any of the 24 food allergens ranged from 24.6% in Portland (USA) to 7.7% in Reykjavik (Iceland). With few exceptions, the relative prevalence of sensitization to different foods was similar in all countries. Sensitization rates to egg, fish and milk were each less than 1%, and the most common sensitizations are not represented in current commercial mixes. The prevalence of sensitization to foods was not related to that of sensitization to aeroallergens but was related to the geometric mean total IgE for the country. Conclusions:, Sensitization to foods is common but highly variable. The relative prevalence of sensitization to different foods is more consistent than would be expected by chance, suggesting that quantity of consumption of specific foods does not determine prevalence. The aetiology of food sensitization is only partly similar to that for aeroallergens but is related to local levels of total IgE. This may provide an important clue to the origins of food sensitization. [source] State of the art and new horizons in the diagnosis and management of egg allergyALLERGY, Issue 3 2010A. H. Benhamou To cite this article: Benhamou AH, Caubet J-C, Eigenmann PA, Nowak-We,grzyn A, Marcos CP, Reche M, Urisu A. State of the art and new horizons in the diagnosis and management of egg allergy. Allergy 2010; 65: 283,289. Abstract Egg allergy is one of the most frequent food allergies in children below the age of three. Common symptoms of egg allergy involve frequently the skin as well as the gut and in more severe cases result in anaphylaxis. Non-IgE-mediated symptoms such as in eosinophilic diseases of the gut or egg-induced enterocolitis might also be observed. Sensitization to egg white proteins can be found in young children in absence of clinical symptoms. The diagnosis of egg allergy is based on the history, IgE tests as well as standardized food challenges. Ovomucoid is the major allergen of egg, and recent advances in technology have improved the diagnosis and follow-up of patients with egg allergy by using single allergens or allergens with modified allergenic properties. Today, the management of egg allergy is strict avoidance. However, oral tolerance induction protocols, in particular with egg proteins with reduced allergenic properties, are promising tools for inducing an increased level of tolerance in specific patients. [source] Food allergy and food sensitization in early childhood: results from the DARC cohortALLERGY, Issue 7 2009E. Eller Background:, The prevalence of food hypersensitivity (FHS) and the relationship with atopic dermatitis (AD) is controversial. The aim of this study was to determine the development of FHS and to correlate this with AD in relation to sensitization and symptoms. Methods:, This study combines new data from birth to 18 months of age with previous published results from 3 and 6 years. The Danish Allergy Research Centre cohort, including 562 children, is a unique, population-based, prospective birth cohort, with clinical examinations at all follow-ups. All children were examined for the development of AD using Hanifin-Rajka criteria and for FHS using interviews, skin prick test (SPT), specific immunoglobulin E (IgE), and food challenge according to EAACI guidelines. Results:, Twenty children were confirmed with FHS to milk, egg, and peanut. FHS peaked at 18 months (3.6%) and then decreased to 1.2% at 72 months of age. No new cases were found after 3 years. Self-reporting could only be confirmed in 31% of cases. Among the 122 children with AD, 18 had FHS (14.8%). FHS was IgE-mediated in 95% of the cases but 16 of 20 children were additionally sensitized to other foods which they tolerated. Children with AD were neither more IgE-sensitized nor had higher levels of IgE when compared with healthy children but they were more persistently sensitized. Conclusions:, Sensitization to foods in young children without food allergy seems to be a normal phenomenon. The discrepancy between sensitization, self-reported food-related symptoms and confirmed FHS illustrates the need to perform standardized oral challenges in order to confirm the diagnosis of FHS. [source] Dual sensitization to rat and mouse urinary allergens reflects cross-reactive molecules rather than atopyALLERGY, Issue 6 2009H. Jeal Background:, Sensitization to rats and mice can develop in laboratory animal workers exposed to only one species. Reasons for this dual sensitization are unclear but may reflect a genetic predisposition to developing allergy (atopy) or alternatively cross-reactivity between rat and mouse urinary allergens. We examined cross-reactivity between rat and mouse urine and the effect atopy has on dual sensitization in laboratory animal workers. Methods:, In a cross-sectional study the frequency of sensitization to rat and/or mouse was analysed in 498 employees exposed to both rat and mouse at work and 220 to rat only. RAST inhibitions, western blots and blot inhibitions were carried out on a subset of five individuals to assess cross-reactivity. Results:, Fourteen per cent of workers were sensitized to rats and 9% to mouse. Over half (62%) of rat sensitized individuals were also mouse sensitized and the majority (91%) of mouse sensitized individuals were also rat sensitized. IgE cross-reactivity was demonstrated between rat and mouse urine using RAST inhibitions. Rates of atopy did not differ between rat only sensitized individuals compared with those sensitized to both species. Sensitization to cats and rabbits was more common amongst those with dual sensitization. Conclusions:, Dual sensitization to rat and mouse reflects IgE cross-reactivity rather than atopy. Individuals with dual sensitization are more likely to be sensitized to other animal allergens. These findings will have implications for individuals working with only one rodent species who develop sensitization and symptoms to be aware of the potential for allergy to other species. [source] Sensitization, asthma and allergic disease in young soccer playersALLERGY, Issue 4 2009M. T. Ventura Background:, The aim of this study was to identify the prevalence of allergic disease in young soccer players compared to age-matched students and to evaluate if this prevalence changes as the intensity of training increases. Methods:, A modified ECRHS questionnaire was administered to 194 soccer players divided by age as Beginners (8,11 years), Juniors (12,16 years) and Under 21 (17,20 years) to evaluate the prevalence of allergic diseases and symptoms as well as drug consumption. Subjects with a positive personal history of allergic diseases underwent skin prick and/or patch tests. Age-matched students (n = 136) were used as a control group. Results:, The prevalence of allergic diseases was 34.5% in soccer players and 31.6% in control subjects (n.s.). Skin sensitization to inhalant allergens was detected in 14.4% of symptomatic soccer players and in 19.2% of control students (n.s.). Patch tests were positive in 35.7% of soccer players and 23.0% of controls with allergic dermatitis (n.s.). The prevalence of allergic diseases did not significantly change in relation to the intensity of training. Although the relative prevalence of sensitization to perennial allergens and asthma was less frequent in soccer players than in controls, and the occurrence of exercise-induced bronchoconstriction was similar in the two groups, soccer players used twice as many anti-allergic and anti-asthmatic drugs as control students. Conclusions:, An increasingly intensive training programme is not associated with greater risk of allergic disease in soccer players. Therapy regimens of allergic athletes and exercisers should be monitored more closely to guarantee adequate treatment yet avoid inappropriate drug use and doping practices. [source] Symptoms to pollen and fruits early in life and allergic disease at 4 years of ageALLERGY, Issue 11 2008X.-M. Mai Background:, The predictive value of reported early symptoms to pollen or fruits on later allergic disease is unclear. Our aim is to evaluate if symptoms to pollen and/or to fruits early in life are associated with allergic disease and sensitization to pollen at 4 years. Methods:, The study included 3619 children from the Barn (Children), Allergy, Milieu, Stockholm, Epidemiology project (BAMSE) birth cohort. Reported symptoms of wheeze, sneeze or rash to birch, grass or weed, symptoms (vomiting, diarrhea, rash, facial edema, sneeze, or wheeze) to fruits including tree-nuts at 1 or 2 years of age, and definitions of asthma, rhinitis and eczema at 4 years were derived from questionnaire data. Sensitization to pollen allergens was defined as allergen-specific IgE-antibodies to any pollen (birch/timothy/mugwort) ,0.35 kUA/l. Results:, At 1 or 2 years of age, 6% of the children were reported to have pollen-related symptoms, 6% had symptoms to fruits, and 1.4% to both pollen and fruits. Children with symptoms to both pollen and fruits at 1 or 2 years of age had an increased risk for sensitization to any pollen allergen at age 4 (ORadj = 4.4, 95% CI = 2.1,9.2). This group of children also had a substantially elevated risk for developing any allergic disease (asthma, rhinitis, or eczema) at 4 years irrespective of sensitization to pollen (ORadj = 8.6, 95% CI = 4.5,16.4). Conclusions:, The prevalence of reported symptoms to pollen and fruits is very low in early childhood. However, children with early symptoms to both pollen and fruits appear to have a markedly elevated risk for allergic disease. [source] |