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Patch testing in children, adults, and the elderly: influence of age and sex on sensitization patterns.

Patch testing was done on 2776 consecutive patients (76.5% female) with a locally revised standard series of 34 contact allergens and the results analyzed for age- and gender-specific differences. At least one positive epicutaneous test reaction occurred in 48.9% of patients. Nickel (20.9%), ethylmercuric chloride (13.2%), thimerosal (11.8%), fragrance mix (9.3%), metallic mercury (8.9%), palladium (5.8%), balsam of Peru (3.8%), copper (3.7%), cobalt (3.3%), and chromium (2.3%) were the 10 most important sensitizers. The following tested allergens with sensitization rates of more than 1% were not part of the usual standard series: ethylmercuric chloride, metallic mercury, copper, propolis (1.3%), propylene glycol (1.0%). Reactions to nickel, cobalt, and palladium, but not to chromium, were significantly more abundant in females (p < 0.002, chi-squared test). The overall sensitization rate was highest in children less than 10 years old (62%) and decreased steadily, to be lowest among patients more than 70 years old (34.9%). The rate of positive reactions to nickel and thimerosal decreased with age, while fragrance mix and metallic mercury stayed at the same level through all age groups.

Adolescent↗

A veterinary approach to the European honey bee (Apis mellifera)

The European honey bee (Apis mellifera) has the unusual status of being an inherently wild species from which a natural foodstuff (honey) is derived by manipulating its behaviour to deposit this in man-made wooden frames. Bees also produce propolis and Royal Jelly which can be harvested but their most important effect is one not immediately obvious as an economic product: that of pollination. Bee diseases are predominantly infectious and parasitic conditions accentuated by the close confinement in which they congregate, either in man-made hives or in colonies in a natural cavity. Treatment or at least control of some of these conditions can be attempted. In some cases natural bee behavioural traits limit the effect of the disease while in others, such as the notifiable disease American foulbrood, destruction of the colony is the only method of control. The mite Varroa jacobsoni can be controlled by the synthetic pyrethroids flumethrin and tau-fluvalinate. The introduction of these products has heightened veterinary interest in this important invertebrate species.

Animal Diseases↗

Social exploitation of vitellogenin.

Vitellogenin is a female-specific glucolipoprotein yolk precursor produced by all oviparous animals. Vitellogenin expression is under hormonal control, and the protein is generally synthesized directly before yolk deposition. In the honeybee (Apis mellifera), vitellogenin is not only synthesized by the reproductive queen, but also by the functionally sterile workers. In summer, the worker population consists of a hive bee group performing a multitude of tasks including nursing inside the nest, and a forager group specialized in collecting nectar, pollen, water, and propolis. Vitellogenin is synthesized in large quantities by hive bees. When hive bees develop into foragers, their juvenile hormone titers increase, and this causes cessation of their vitellogenin production. This inverse relationship between vitellogenin synthesis and juvenile hormone is opposite to the norm in insects, and the underlying proximate processes and life-history reasons are still not understood. Here we document an alternative use of vitellogenin by showing that it is a source for the proteinaceous royal jelly that is produced by the hive bees. Hive bees use the jelly to feed larvae, queen, workers, and drones. This finding suggests that the evolution of a brood-rearing worker class and a specialized forager class in an advanced eusocial insect society has been directed by an alternative utilization of yolk protein.

Animals↗

Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B.

Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is known to have antimitogenic, anticarcinogenic, antiinflammatory, and immunomodulatory properties. The molecular basis for these diverse properties is not known. Since the role of the nuclear factor NF-kappa B in these responses has been documented, we examined the effect of CAPE on this transcription factor. Our results show that the activation of NF-kappa B by tumor necrosis factor (TNF) is completely blocked by CAPE in a dose- and time-dependent manner. Besides TNF, CAPE also inhibited NF-kappa B activation induced by other inflammatory agents including phorbol ester, ceramide, hydrogen peroxide, and okadaic acid. Since the reducing agents reversed the inhibitory effect of CAPE, it suggests the role of critical sulfhydryl groups in NF-kappa B activation. CAPE prevented the translocation of the p65 subunit of NF-kappa B to the nucleus and had no significant effect on TNF-induced I kappa B alpha degradation, but did delay I kappa B alpha resynthesis. The effect of CAPE on inhibition of NF-kappa B binding to the DNA was specific, in as much as binding of other transcription factors including AP-1, Oct-1, and TFIID to their DNA were not affected. When various synthetic structural analogues of CAPE were examined, it was found that a bicyclic, rotationally constrained, 5,6-dihydroxy form was superactive, whereas 6,7-dihydroxy variant was least active. Thus, overall our results demonstrate that CAPE is a potent and a specific inhibitor of NF-kappa B activation and this may provide the molecular basis for its multiple immunomodulatory and antiinflammatory activities.

Base Sequence↗

Stimulatory actions of caffeic acid phenethyl ester, a known inhibitor of NF-kappaB activation, on Ca2+-activated K+ current in pituitary GH3 cells.

Caffeic acid phenethyl ester (CAPE), a phenolic antioxidant derived from the propolis of honeybee hives, is known to be an inhibitor of activation of nuclear transcript factor NF-kappaB. Its effects on ion currents have been investigated in pituitary GH(3) cells. This compound increased Ca(2+)-activated K(+) current (I(K(Ca))) in a concentration-dependent manner with an EC(50) value of 14 +/- 2 microm. However, the magnitude of CAPE-induced stimulation of I(K(Ca)) was attenuated in GH(3) cells preincubated with 2,2'-azo-bis-(2-amidinopropane) hydrochloride (100 microm) or t-butyl hydroperoxide (1 mm). CAPE (50 microm) slightly suppressed voltage-dependent L-type Ca(2+) current. In inside-out configuration, CAPE (20 microm) applied to the intracellular face of the detached patch enhanced the activity of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels with no modification in single-channel conductance. After BK(Ca) channel activity was increased by CAPE (20 microm), subsequent application of nordihydroguaiaretic acid (20 microm) did not further increase the channel activity. CAPE-stimulated channel activity was dependent on membrane potential. CAPE could also increase Ca(2+) sensitivity of BK(Ca) channels in these cells. Its increase in the open probability could primarily involve a decrease in the mean closed time. In current-clamp conditions, CAPE hyperpolarized the membrane potential and reduced the firing of action potentials. The stimulatory effects on these channels may partly contribute to the underlying mechanisms through which this compound influences the functional activities of neurons or neuroendocrine cells. Caution has to be used in attributing its response in the activation of NF-kappaB.

Amidines↗

Effect of caffeic acid phenethyl ester on corneal neovascularization in rats.

PURPOSE: Caffeic acid phenethyl ester (CAPE), a biologically active component of propolis from honeybee hives, has potent antiinflammatory and antioxidant properties. We aimed to evaluate the ability of topically applied CAPE in comparison with known steroidal (dexamethasone sodium phosphate) and nonsteroidal (indomethacin) topical agents to reduce corneal neovascularization (CNV) induced by silver nitrate cauterization in rats. METHODS: Following silver nitrate cauterization on both eyes, male rats were randomly assigned to the study and control groups, each consisting of ten rats. The inhibitory effects of the test drugs against a placebo (isotonic saline) on CNV were tested and compared to each other using a previously described method in which extent of neovascularization and burn stimulus intensity were scored by a masked examiner. Briefly, burn stimulus intensity was scored from 0 to +3 according to the height of blister from corneal surface, and extent of neovascularization was recorded from 0 to +6 according to the distance from limbus to the end point of CNV toward the central corneal burn. Results. The mean burn stimulus score were not different among the groups (P = 0.807). Percent inhibition of CNV compared to the placebo control and its significance were 31.5 %, P = 0.011 for indomethacin; 56 %, P < 0.001 for dexamethasone; and 52 %, P < 0.001 for CAPE. Dexamethasone was significantly (P < 0.05) more effective than indomethacin in inhibition of neovascular growth. CAPE was found to be superior (P < 0.05) to indomethacin and almost as effective as (P > 0.05) dexamethasone in reducing CNV. Conclusion. Topically applied CAPE was demonstrated to have an inhibitory effect, comparable to that of topical dexamethasone, on CNV in this rat model. Antiinflammatory and antioxidant properties of CAPE may contribute to its suppression on CNV.

Administration, Topical↗

Honeybee, Apis mellifera (Hymenoptera: Apidae), leaf damage on Alnus species in Uganda: a blessing or curse in agroforestry?

It is a dictum that Apis mellifera Linnaeus is innocuous in agricultural ecosystems. This study provides the first record of A. mellifera as a significant defoliator of Alnus species. Careful field observations coupled with microscopic examination provided convincing evidence implicating A. mellifera as the cause of leaf perforation on Alnus species in Uganda. Apis mellifera was observed foraging selectively on young Alnus leaves and buds in search of a sticky substance, apparently propolis. In so doing, the bee created wounds that enlarged and caused tattering of Alnus leaves as they matured. Biological surveys indicated that the damage was prevalent and occurred widely, particularly on Alnus acuminata Kunth in Uganda. Incidence of the Apis mellifera damage on Alnus acuminata peaked in the dry season, with up to 90% of leaves emerging per shoot per month damaged, and was lowest in the wet months during peak leaf emergence. Apis mellifera leaf damage was consistently higher on Alnus acuminata than A. nepalensis D. Don., on saplings than mature trees, and on sun exposed than shaded leaves. The activity of honeybees may be detrimental to the productivity of Alnus, yet the substance for which the insect forages on Alnus is a resource with potential economic importance.

Agriculture↗

Oleic acid-induced lung injury in rats and effects of caffeic acid phenethyl ester.

Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant and is an active anti-inflammatory component of honeybee propolis. The authors evaluated the effects of CAPE on oxidative stress and lung damage in an oleic acid (OA)-induced lung-injury model. Rats were divided into 5 groups as sham, OA, CAPE, pre-OA-CAPE, and post-OA-CAPE. Acute lung injury was induced by intravenous administration of 100 mg/kg of OA. Pre-OA-CAPE group received CAPE (10 micromol/kg. intravenously) 15 minutes before OA infusion and post-OA-CAPE group received CAPE 2 hours after OA administration. Malondialdehyde (MDA) level of plasma, bronchoalveolar lavage fluid (BALF), and lung tissue; myeloperoxidase activity of BALF and lung tissue; Na(+)-K(+) ATPase activity of lung tissue; and total protein content of BALF were measured. Light microscopic analyses of lung specimens were performed. The increased MDA levels in lung homogenates (47.98+/-13.75 nmol/mL), BALF (31.12+/-3.07 nmol/mL), and plasma (61.84+/-15.34 nmol/mL) decreased significantly to 24.33+/-3.09 nmol/mL (P = 0.000), 23.19+/-4.97 nmol/mL (P = 0.002), and 27.36+/-5.37 nmol/mL (P = 0.000), respectively, following CAPE administration in pre-OA-CAPE group. Another important finding was the restoration of the enzymatic activity of Na(+)-K(+) ATPase from a value of 203.89+/-32.18 nmol Pi/mg Protein/h in OA group, to a value of 302.17+/-51.90 nmol Pi/mg Protein/h (P = 0.012) in pre-OA-CAPE group with CAPE treatment. CAPE has been shown to have a clear attenuating effect on oxidative damage in experimental animal studies. However, further investigations are necessary to suggest CAPE as a treatment agent in critically ill patients with lung injury.

Animals↗

Determination and confirmation of methyl p-hydroxybenzoate in royal jelly and other foods produced by the honey bee.

Methyl p-hydroxybenzoate (methyl paraben) in foods produced by the Honey Bee was determined by HPLC and confirmed by GC-MS. The compound was detected at a mean concentration of 22.3 +/- 6.8 mg/kg (between 14.2 and 31.9 mg/kg) in commercial royal jelly, but was not detected in honey, propolis or pollen lumps at the detection limit of 1 mg/kg. Fresh royal jelly collected from apiaries contained methyl p-hydroxybenzoate at a concentration of 20.3 +/- 4.7 mg/kg (between 12.5 and 31.7 mg/kg). These results indicate that the methyl p-hydroxybenzoate in royal jelly is not added but is a natural component.

Animals↗

Effect of caffeic acid phenethyl ester on survival of axial pattern flaps in rats with ischaemia-reperfusion injuries.

Oxygen-derived free radicals have been implicated in the pathogenesis of tissue injury after ischaemia-reperfusion. Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having potent antioxidant and anti-inflammatory properties. We evaluated the ability of CAPE applied intraperitoneally in reducing tissue injury after ischaemia-reperfusion. To investigate whether treatment with CAPE modifies the concentrations of the endogenous indices of oxidant stress, we examined its effects on a model of flap ischaemia-reperfusion injury in rats. CAPE (10 micromol/kg) was given through the peritoneum before reperfusion. CAPE given intraperitoneally had an inhibitory effect on tissue injury after ischaemia-reperfusion comparable to that of a control group. The anti-inflammatory and antioxidant properties of CAPE may contribute to its suppression of tissue injury.

Animals↗

In vitro antioxidant profile of phenolic acid derivatives.

Several caffeic acid esters isolated from propolis exhibit interesting antioxidant properties, but their in vivo use is compromised by hydrolysis of the ester bond in the gastrointestinal tract. Therefore, a series of caffeic acid amides were synthesized and their in vitro antioxidant profile was determined. A series of hydroxybenzoic acids, hydroxycinnamic acids, and the synthesized caffeic acid amides were tested for both their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and microsomal lipid peroxidation-inhibiting activity. Some of the highly active antioxidants were further tested by means of electron paramagnetic resonance for their hydroxyl radical scavenging activity. Since a promising antioxidant compound should show a lipid peroxidation-inhibiting activity at micromolar level and a low cytotoxicity, the cytotoxicity of the phenolic compounds was also studied. In all the assays used, the caffeic acid anilides and the caffeic acid dopamine amide showed an interesting antioxidant activity.

Antioxidants↗

Caffeic acid phenethyl ester prevents neonatal hypoxic-ischaemic brain injury.

Neonatal hypoxic-ischaemic (HI) brain injury resulting in encephalopathy is a leading cause of morbidity and mortality with no effective treatment. Here we show that caffeic acid phenethyl ester (CAPE), an active component of propolis, administered either before or after an HI insult, significantly prevents HI-induced neonatal rat brain damage in the cortex, hippocampus and thalamus. In addition to blocking HI-induced caspase 3 activation, CAPE also inhibits HI-mediated expression of inducible nitric oxide synthase and caspase 1 in vivo and potently blocks nitric oxide-induced neurotoxicity in vitro. Furthermore, CAPE directly inhibits Ca2+-induced cytochrome c release from isolated brain mitochondria. Thus, CAPE induces neuroprotection against HI-induced neuronal death, possibly by blocking HI-induced inflammation and/or directly inhibiting the HI-induced neuronal death pathway. CAPE may therefore be a novel effective therapy for preventing neonatal HI injury.

Animals↗

Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA, RNA and protein in HeLa cells.

Topical application of caffeic acid phenethyl ester (CAPE), a constituent of the propolis of honeybee hives, to the backs of CD-1 mice previously initiated with 7,12-dimethylbenz[a]anthracene (DMBA) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion and the formation of 5-hydroxymethyl-2'-deoxyuridine (HMdU) in epidermal DNA. Topical application of 5 nmol TPA twice weekly for 20 weeks to mice previously initiated with 200 nmol of DMBA resulted in 18.8 skin papillomas per mouse. Topical application of 1, 10, 100 or 3000 nmol of CAPE together with 5 nmol of TPA twice a week for 20 weeks inhibited the number of skin papillomas per mouse by 24, 30, 45 or 70%, respectively, and tumor size per mouse was decreased by 42, 66, 53 or 74%, respectively. Topical application of 5 nmol of TPA twice weekly for 20 weeks to mice previously initiated with DMBA produced an average of 12.6 HMdU residues per 10(4) normal bases in epidermal DNA. Topical application of 1, 10, 100 or 3000 nmol of CAPE with 5 nmol of TPA twice weekly for 20 weeks to DMBA-initiated mice decreased the level of HMdU in epidermal DNA by 40-93%. The in vitro addition of 1.25, 2.5, 5, 10 or 20 microM CAPE to cultured HeLa cells inhibited the synthesis of DNA by 32, 44, 66, 79 or 95%, respectively, the synthesis of RNA was inhibited by 39, 43, 58, 64 or 75%, respectively, and the synthesis of protein was inhibited by 29, 30, 37, 32 or 47%, respectively. The results indicate a potent inhibitory effect of CAPE on TPA-induced tumor promotion and TPA-induced formation of HMdU in DNA of mouse skin as well as an inhibitory effect of CAPE on the synthesis of DNA, RNA and protein in culture HeLa cells.

9,10-Dimethyl-1,2-benzanthracene↗

The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells.

Caffeic acid phenethyl ester (CAPE), an active component of propolis, has many biological and pharmacological activities including antioxidation and tumor cell cytotoxicity. We examined the type of cell death in human leukemic HL-60 cells after CAPE treatment in order to elucidate the relationship between CAPE-induced alterations of the redox state and apoptosis. CAPE treatment (6 microg/ml) resulted in marked growth inhibition up to 70.3+/-4.0% at day 2. This inhibition was partially blocked by pretreatment with N-acetyl-L-cycteine (NAC). Agarose gel electrophoresis showed evident DNA fragmentation after CAPE treatment. CAPE induced a significant decrease in mitochondrial transmembrane potential to about half of the untreated level after 6 h and a rapid depletion of intracellular glutathione (GSH) down to 41.7+/-6.0% after 1 h. Pretreatment of HL-60 cells with NAC reversed the GSH depletion and partially rescued cells from CAPE-induced apoptosis. With regard to intracellular reactive oxygen species, CAPE caused a fast and profound scavenging of H202 (19% of untreated cells after a 2-h treatment) but not of superoxide anion. These results suggest that apoptosis induced by CAPE is associated with mitochondrial dysfunction, GSH depletion and selective scavenging of H2O2 in human leukemic HL-60 cells.

Acetylcysteine↗

Caffeic acid phenethyl ester induces growth arrest and apoptosis of colon cancer cells via the beta-catenin/T-cell factor signaling.

Caffeic acid phenethyl ester, an active component of propolis, has been implicated in the regulation of cell growth and apoptosis, although the exact mechanism of this activity has not been elucidated. In this study, we explored the effects of caffeic acid phenethyl ester on growth, cell cycle, apoptosis and beta-catenin/T-cell factor signaling in human colon cancer cells. Using two human sporadic colon cancer cell lines (HCT116 and SW480), we assayed for cell growth inhibition, cell cycle and apoptosis induction. We also assayed for beta-catenin and downstream target genes (cyclin D1 and c-myc) mRNA and protein expression by reverse transcriptase-polymerase chain reaction and Western blot analysis. Beta-catenin localization was detected by indirect immunofluorescence. Beta-catenin/T-cell factor transcriptional activity was determined by transient transfection and reporter gene assay. Caffeic acid phenethyl ester completely inhibited growth, and induced G1 phase arrest and apoptosis in a dose-dependent manner in both HCT116 and SW480 cells. Treatment of human colon cancer cells with apoptotic concentrations of caffeic acid phenethyl ester resulted in a dose-dependent and time-dependent loss of total beta-Catenin protein, associated with decreased nuclear beta-catenin. Caffeic acid phenethyl ester reduced the expression of cyclin D1 and c-myc in a dose-dependent and time-dependent manner. We proved that caffeic acid phenethyl ester markedly suppressed the transcriptional activity of beta-catenin/T-cell factor in both HCT116 and SW480 cells depending on the concentration of caffeic acid phenethyl ester. These results indicate that caffeic acid phenethyl ester is an excellent inhibitor of beta-catenin/T-cell factor signaling in colon cancer cell lines and suggest that caffeic acid phenethyl ester merits further study as an agent against colorectal cancers.

Annexin A5↗

Starmerella meliponinorum sp. nov., a novel ascomycetous yeast species associated with stingless bees.

Thirty-two strains of the novel species Starmerella meliponinorum sp. nov. were isolated from various substrates associated with three stingless bee species (tribe Meliponini) in Brazil and one in Costa Rica. The strains were found in garbage pellets (faecal material, discarded pollen or food, etc.), pollen provisions, adult bees, honey and propolis of Tetragonisca angustula, in honey from Melipona quadritasciata and in adults of Melipona rufiventris and Trigona fulviventris. The sequence of the D1/D2 domains of the large-subunit rDNA showed that the novel species belongs to the Starmerella clade and is most closely related to Candida etchellsii, although the two differ in their sequences by 7% base substitutions. S. meliponinorum is homothallic and assimilates few carbon sources. Nitrate is utilized as a sole nitrogen source. The type strain of S. meliponinorum is strain UFMG-01-J26.1T (=CBS 9117T).

Animals↗

Protective role of caffeic acid phenethyl ester in the liver of rats exposed to cold stress.

Cold exposure can induce a form of environmental stress. Cold stress (CS) alters homeostasis, results in the creation of reactive oxygen species and leads to alterations in the antioxidant defense system. The caffeic acid phenethyl ester (CAPE), an active component of propolis, has an antioxidant capacity. We investigated the effect of CS on oxidative stress and antioxidant defense system and the possible protective effect of CAPE in rat liver tissue. Twenty-four female Wistar Albino rats were divided into four groups: Control, CAPE-treated, CS, and CAPE-treated CS (CS + CAPE) group. Catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activities and total glutathione (GSH) and malondialdehyde (MDA) levels were measured. In addition, histological changes in liver tissue were examined by light microscopy. SOD, CAT and GSH-Px activities and total GSH level were significantly declined in the CS group. In the CS + CAPE group, the activities of these three enzymes and GSH level significantly raised with regard to the CS group. MDA levels increased in the CS group and decreased in the CS + CAPE group. The tissues of the CS group showed some histopathological changes such as necrosis, hepatocyte degeneration, sinusoidal dilatation, hemorrhage and vascular congestion and dilatation. In the CS + CAPE group, the histopathological evidence of hepatic damage was markedly reduced. Histological parameters were consistent with biochemical parameters. In this study, CS increased oxidative stress in liver tissue. CAPE regulated antioxidant enzymes, inhibited lipid peroxidation and reduced hepatic damage.

Animals↗

Contact sensitization in 1094 children undergoing patch testing over a 7-year period.

Contact sensitization in children is frequent. However, because exposure to sensitizing agents varies rapidly, it is of utmost importance to perform a periodic evaluation of patch test results. Our purpose was to compare our data on contact sensitization in children during the past 7 years to our previous 1988-1994 findings, in order to identify emerging allergens and update our pediatric series. From 1995 to 2001, 1094 consecutive children were examined. Of these, 997 patients were patch tested with our pediatric series, which includes 30 allergens, whereas 97 underwent patch testing with 46 allergens. A total of 570 children proved allergic (52.1%). The highest sensitization rate was observed in children under 3 years of age. No differences between atopic dermatitis patients and nonatopic ones were observed in the sensitization rate. Neomycin, nickel, wool alcohols, thimerosal, and ammoniated mercury gave most of the positive responses. With respect to 1988-1995 data, allergy to substances such as neomycin, nickel, wool alcohols, thimerosal, ammoniated mercury, propolis, potassium dichromate, and thiuram mix proved more frequent. In conclusion, as sensitization rates to different allergens show great variations over time, periodic evaluations of patch test results in children is necessary in order to update the test trays.

Allergens↗