Contact hypersensitivity in adolescents.

BACKGROUND: Contact hypersensitivity is common in adolescents, but data in the literature are limited. Adolescents often use cosmetics, wear jewelry, and obtain tattoos, which can be sources of allergens. METHODS: This was a retrospective, noninterventional cohort study of 100 adolescents (aged 13-18; 74 girls, 26 boys) who were consecutively patch tested. RESULTS: We detected contact hypersensitivity in 51 of the 100 patch-tested patients (51%): 52.7% of the girls and 46.2% of the boys were sensitized. The most common allergens were nickel (17%), thimerosal (12%), para-phenylenediamine (8%), cobalt (7%), and fragrance mix I (6%). Thirteen percent of the reactions did not appear until the seventh day. The majority of clinical lesions affected the hands and face. The most common contact allergens were mercury derivatives, lanolin, and para-phenylenediamine in boys and nickel, thimerosal, para-phenylenediamine, cobalt, and fragrance mix I in girls. Of the 47 adolescents with atopic dermatitis 51.1% had contact hypersensitivity. In this group, skin care product ingredients were the typical allergens (25.5%). The most common contact allergens of those with atopic dermatitis were nickel (12.8%), lanolin (10.6%), and thimerosal (8.5%). CONCLUSION: Contact hypersensitivity is common in adolescents. For patients with therapy-resistant skin lesions affecting the face and hands, patch testing with an evaluation for 7 days is recommended. Our results provide the first data on frequency of contact hypersensitivity in this age group in Hungary. Metals, fragrances, mercuric derivatives, dyeing materials, and skin care products were the most common allergens.

para-Phenylenediamine Hypersensitivity: A Report From Budapest, Hungary, 2007-2014.

BACKGROUND: para-Phenylenediamine (PPD) is a potent allergen with frequent exposure through use of hair dyes or henna tattoos. OBJECTIVES: We wished to determine if prevalence of PPD sensitivity is changing through time as trends in its use change. PATIENTS: A total of 3631 patients were patch tested consecutively with the environmental standard series between 2007 and 2014 to map the prevalence of PPD sensitivity and its distribution according to age, sex, and diagnosis. RESULTS: Two hundred nine patients (5.75%) were proven to be PPD sensitive. Most PPD-sensitive patients were approximately in their 60s in 2007, whereas in 2014, they were in their 20s and 30s. In 2014, 61.1% of the patients were younger than 35 years and 50% were younger than 25 years. Of 209 PPD-sensitive patients, 32.5% had present relevance related to hair dyeing and eyebrow or eyelash coloring procedures. All affected male patients were hairdressers. Adverse reaction to henna was detected in only 1 case after henna hair dye use. CONCLUSIONS: The 5.75% prevalence of PPD sensitization in our study was higher compared with that in the European data. It is alarming that PPD hypersensitivity occurred even among teenagers. This may be mainly explained by hair dyeing at an early age.

Methylchloroisothiazolinone/Methylisothiazolinone and Methylisothiazolinone Sensitivity in Hungary.

Background. Due to allowing of methylisothiazolinone (MI) in cosmetics, cleaning products, and paints, an epidemic of MI-hypersensitivity emerged. Patch testing Kathon CG® (3:1 mixture of methylchloroisothiazolinone and methylisothiazolinone, MCI/MI) does not correctly detect MI contact allergy, due to the low concentration of MI in the test material. Methods. A retrospective survey was performed to estimate the prevalence of MCI/MI hypersensitivity in 14693 patients tested consecutively between 1993 and 2014. Moreover, currently 314 patients were prospectively tested with the allergens MCI/MI and with MI during one year. Results. MCI/MI hypersensitivity increased retrospectively from 0.5% to 6.0%. By current prospective testing we detected 25 patients (8%) with MCI/MI and/or MI positive reactions. Out of the 25 patients 10 were only MCI/MI positive, 9 were only MI positive, and 6 were MCI/MI and MI positive. If MI had not been tested separately, MI contact allergy would have missed in 36% of all detected cases and in 2.8% of the total 314 patients. Conclusions. The frequency of MCI/MI hypersensitivity is increasing also in Hungary. We confirm that, in order to detect MI contact allergy, it needs to be tested separately. A further increase of MI hypersensitivity might be expected in the future as products containing MI are still widely available.

[Effect of diabetes on the relation between troponin T and inflammatory markers in patients on hemodialysis]. / A diabetes hatása a troponin T és a gyulladásos markerek kapcsolatára hemodializált betegekben.

INTRODUCTION: Cardiac troponin T in renal failure is used for the assessment of cardiovascular risk and mortality. Elevated cardiac troponin T levels correlate with subclinical myocardial necrosis, coronary heart disease, several echocardiographic parameters, metastatic calcification, as well as the presence of diabetes and uremic toxins. AIM: The aim of the authors was to examine the impact of factors, mainly the independent effects of inflammatory laboratory parameters, which may influence hypersensitive troponin T levels in hemodialysed patient groups with and without diabetes. METHOD: Hemodialysed patient groups with (n = 44) and without diabetes (n = 76) were studied. Difference in serum hypersensitive troponin T values before and after dialysis were analysed by paired Wilcoxon test. Factors possibly affecting the level of hypersensitive troponin T (especially inflammatory markers) were evaluated by multiregression analysis. RESULTS: Hypersensitive troponin T levels in patients without diabetes (p = 0.0003) and those with diabetes (p = 0.0032) significantly increased during hemodialysis. In patients without diabetes several factors had significant effect on hypersensitive troponin T including age (p = 0.025), duration of hemodialysis (p = 0.0002), presence of cardiovascular complications (p = 0.0002), high sensitivity C-reactive protein (p = 0.0021), white blood cell count (p = 0.038), and the monocyte ratio (p = 0.0202). However, in patients with diabetes only high sensitivity C-reactive protein (p = 0.0024) showed association with hypersensitive troponin T levels. CONCLUSIONS: In hemodyalised patients with and without diabetes the hypersensitive troponin T levels are differently influenced by clinical and inflammatory laboratory parameters, which should be taken into consideration during clinical judgement.

Reduced inflammatory threshold indicates skin barrier defect in transglutaminase 3 knockout mice.

Recently, a transglutaminase 3 knockout (TGM3/KO) mouse was generated that showed impaired hair development, but no gross defects in the epidermal barrier, although increased fragility of isolated corneocytes was demonstrated. Here we investigated the functionality of skin barrier in vivo by percutaneous sensitization to FITC in TGM3/KO (n=64) and C57BL/6 wild-type (WT) mice (n=36). Cutaneous inflammation was evaluated by mouse ear swelling test (MEST), histology, serum IgE levels, and by flow cytometry from draining lymph nodes. Inflammation-induced significant MEST difference (P<0.0001) was detected between KO and WT mice and was supported also by histopathology. A significant increase of CD4+ CD25+-activated T cells (P<0.01) and elevated serum IgE levels (P<0.05) in KO mice indicated more the development of FITC sensitization than an irritative reaction. Propionibacter acnes-induced intracutaneous inflammation showed no difference (P=0.2254) between the reactivity of WT and KO immune system. As in vivo tracer, FITC penetration from skin surface followed by two-photon microscopy demonstrated a more invasive percutaneous penetration in KO mice. The clinically uninvolved skin in TGM3/KO mice showed impaired barrier function and higher susceptibility to FITC sensitization indicating that TGM3 has a significant contribution to the functionally intact cutaneous barrier.

Patch tests with fragrance mix II and its components.

BACKGROUND: Fragrance mix II (FM II) was initiated to detect contact hypersenstitivity (CH) to fragrances that could not have been identified previously. OBJECTIVE: The aim of this multicenter study was to map the frequency of CH to FM II and its components in Hungary. METHODS: Six centers participated in the survey from 2009 to 2010. A total off 565 patients (434 women and 131 men) with former skin symptoms provoked by scented products were patch tested. The tests were performed with Brial GmbH D-Greven allergens. In the environmental patch test series, FM II, FM I, Myroxylon pereirae, colophonium, wood-tar mix, propolis, and sesquiterpene lactone mix were tested as fragrance allergens. The FM II components (citral, farnesol, coumarin, citronellol, α-hexyl-cinnamaldehyde, and hydroxy-isohexyl-3-cyclohexene-carboxaldehyde [Lyral]) were also tested. RESULTS: Contact hypersenstitivity to any fragrances was detected in 28.8%, to FM II in 17.2% of the patients. Contact hypersenstitivity to hydroxy-isohexyl-3-cyclohexene-carboxaldehyde was observed in 7.3%, to coumarin in 5.1%, to α-hexyl-cinnamaldehyde in 3.5%, to citral in 3.4%, to farnesol in 2.5%, and to citronellol in 1.2%. Of the FM II-positive cases, 48.4% showed isolated CH reaction. CONCLUSIONS: The frequency of CH to FM II is 17.2% in the tested, selected Hungarian population. The CH to FM II and its components could not have been revealed without the present test materials.

Heme oxygenase-1 expression in premature and mature neonates during the first week of life.

Newborns are exposed to mechanical and oxidative stress during labor and to relative hyperoxia thereafter during the course of adaptation to the extrauterine conditions. Part of the adaptation mechanism is the rapid degradation of fetal hemoglobin and the oxidation of its heme moiety by heme oxygenases (HOs). Heme oxygenase-1 enzyme (HO-1) is the inducible isoform, which is induced by and protective against oxidative stress. We hypothesized that HO-1 may play a role in the physiological adaptation of newborns. We therefore measured the HO-1 mRNA expression with cRT-PCR during the first week after birth in healthy mature and premature newborns. We found that HO-1 was induced until day 2 or 3 after birth, but its level had dropped below the birth HO-1 mRNA level by the end of the first week. HO-1 levels and inducibility were similar in mature newborns and premature newborns. The fact that HO-1 was inducible even in gestation week 26 suggests that HO-1 plays an important role in the early adaptation processes.

Roles of paraoxonase and oxidative stress in adolescents with uraemic, essential or obesity-induced hypertension.

BACKGROUND/AIMS: Paraoxonase 1 (PON1) is associated with high-density lipoproteins in the plasma, and is capable of hydrolysing oxidized lipids and preventing the oxidation of low-density lipoproteins. Oxidative stress and the PON1 (activity and Q192R polymorphism) were analysed in adolescent patients with essential (n = 49) or obesity-induced hypertension (n = 79), uraemic patients (n = 20), and also in obese normotensive patients (n = 60) and age-matched controls (n = 57). METHODS: The PON1 activity was measured via paraoxon hydrolysis. The PON1 genotype was determined by real-time PCR. The levels of oxidized and reduced glutathione, the end-products of nitric oxide, cysteine, homocysteine and lipid peroxidation in the plasma were measured and related to the PON1 status. RESULTS: There were no significant differences between the patient groups and the control group in the genotype distributions and the allele frequencies of the Q192R polymorphism. The PON activity was significantly lower (p < 0.001) in the uraemic hypertensive group than in the controls. The MDA concentration was significantly higher in the uraemic hypertensive (p < 0.001) and obese hypertensive (p < 0.05) patients. The plasma NOx concentrations were significantly lower (p < 0.001) and the ratio MDA/NOx were significantly higher in all four patient groups. The GSH levels were significantly lower in the patients with hypertension (p < 0.001) and obesity-induced hypertension (p < 0.05) than in the controls, while the GSSG level (p < 0.01) and the ratio GSSG/GSH (p < 0.05) was significantly higher in the uraemic hypertensive group. The plasma homocysteine level was significantly higher (p < 0.001) in the uraemic hypertensive patients as compared with the controls. CONCLUSIONS: We found no significant correlation between the biochemical parameters and neither genotypes nor enzyme activities. The PON1 status and the levels of certain biochemical parameters are independently associated with the hypertension in hypertensive and obese hypertensive patients, and the elevated levels of lipid peroxides and plasma homocysteine may contribute to the increased risk of cardiovascular complications in patients on haemodialysis.

Different pathomechanisms of essential and obesity-associated hypertension in adolescents.

Obesity-induced hypertension and essential hypertension in lean patients are two different forms of hypertension. The main goal of this study was to test whether there are differences in biochemical parameters between subjects with obesity-associated hypertension and those with essential hypertension. We examined whether the biochemical responses to angiotensin-converting enzyme inhibitor (ACEI) ramipril therapy reveal properties of these two conditions that might explain the differences in clinical outcome. Before ramipril therapy, the hypertensive group exhibited increases in ACE activity (p<0.05), plasma malondialdehyde (MDA) concentration and the malondialdehyde/nitric oxide end-product ratio (MDA/NO(x)) (p<0.05), and decreases in xanthine oxidase (XO) activity (p<0.05) and plasma nitric oxide end-product (NO(x)) level (p<0.01). Before medication, plasma endothelin-1 (ET-1), plasma leptin, and leptin receptor levels were normal. Following ramipril treatment, ACE activity normalized. Before ACE inhibitor treatment, the obese-hypertensive group exhibited elevated levels of plasma ET-1 (p<0.05), plasma leptin (p<0.01), XO activity (p<0.05), plasma MDA and MDA/NO(x) (p<0.05), and reduced levels of plasma NO(x)(p<0.01) and leptin receptors (p<0.001). Following medication, the plasma NO(x) level, MDA/NO(x), and XO activity returned to normal while ACE activity decreased (p<0.001). In patients with essential hypertension, NO availability and ACE activity, and in those with obesity-associated hypertension, hyperleptinemic effects, NO level, endothelin-1 concentration and XO activity, may be important factors in the pathology.

Heme oxygenase 1 expression in young uremic patients on hemodialysis.

Oxidative stress plays an important role in the cardiovascular complications in end-stage renal disease (ESRD) patients on long-term hemodialysis (HD). Heme oxygenase-1 (HO-1) inhibits inflammatory events and protects against oxidative stress and endothelial injury. Therefore, we followed the effects of single HD sessions on HO-1 expression. A competitive reverse transcriptase PCR method was used to estimate HO-1 induction before and immediately after HD and 48 h later in 17 young uremic patients. We also measured the concentrations of plasma hemoglobin and bilirubin as indicators of hemolysis, the ferroxidase activity, and the erythrocyte-derived reduced and oxidized glutathione levels as oxidative stress markers, and the homocysteine levels as an independent risk factor. We found significant differences in HO-1 expression patterns in the patients, depending on the duration of HD treatment. Short-term HD [ n=7, median 19 months (9, 29 quartiles)] resulted in an elevated HO-1 expression, which was not further upregulated during HD. Long-term HD [ n=10, median 97 months (53, 150 quartiles)] led to downregulation of baseline HO-1 expression in ESRD patients. In these patients, a single HD session results in erythrocyte injury and a transient one- to five-fold elevation of HO-1 expression. The chronic downregulation of the baseline expression of HO-1 in long-term HD patients resulted in recurring oxidative stress during each HD session, which may contribute to accelerate the progression of atherosclerosis.

Platelet aggregation, blood viscosity and serum lipids in hypertensive and obese children.

UNLABELLED: A group of 35 patients (median age 15.5 years, range 8-17 years) with juvenile essential hypertension, 15 with body mass index (BMI kg/m(2)) <25 and 20 with BMI >25, as well as 35 age and sex matched controls (BMI <25 n=20; BMI >25 n=15) were investigated to study the role of hypertension and obesity, separately and in combination, on in vitro platelet aggregation, blood and plasma viscosity, plasma lipid concentrations and lipid peroxidation as well as nitric oxide (NO) production. Obese children (hypertensive and controls) had significantly higher concentrations of total cholesterol and triglycerides. The levels of high density lipoprotein (HDL)-cholesterol were lower in obese hypertensive children than their non-obese counterparts. There was a significant increase in platelet aggregation and a decrease in NO levels in hypertensive patients (obese and non-obese) reflecting a significant negative correlation (r=-0.553 and -0.530, n=35; P<0.01, respectively). However, an increased tendency to aggregation was also evident in obese normotensive patients. A significant positive correlation was observed between the platelet aggregation and BMI (r=0.501, n=35; P<0.01). Plasma free thiols were decreased in hypertensive children independent of their BMI. An increased lipid peroxidation and higher blood and plasma viscosity were found only in obese patients with hypertension. Multivariate analysis revealed significant interactions in the effects of obesity and hypertension on platelet aggregation and thiol oxidation. CONCLUSION: in obese children an increased platelet aggregation and oxidative insult contribute to the development of hypertension and to the promotion of vascular damage.

Oxidative stress in juvenile essential hypertension.

OBJECTIVE: Oxidative stress, an antioxidant/pro-oxidant imbalance, in patients with juvenile essential hypertension was measured via several biochemical parameters. As the blood pressure is associated with the body mass index (BMI), results were compared with those on BMI-matched controls. DESIGN AND SETTING: A prospective observational study at a university teaching hospital. PATIENTS: Children and adolescents with essential hypertension (mean standard deviation: age 14.4 +/- 3.1 years, BMI 25.0 +/- 6.9 kg/m(2), n = 52) before any treatment, and controls with a similar BMI distribution (age 14.3 +/- 4.3 years, BMI 24.4 +/- 6.6 kg/m(2), n = 48). METHODS: Measurements were made of the plasma levels of (1) nitrites + nitrates, an indirect measure of available nitric oxide; (2) lipid peroxidation end-products, as malondialdehydes and free thiols; and (3) the redox status of the red blood cell glutathione, as a new oxidative stress parameter. RESULTS: There were decreased plasma levels of nitrates and increased levels of lipid peroxidation end-products in the hypertensive patients, resulting in a consistent increase in the plasma lipid peroxidation/nitric oxide ratio as compared with the controls with the same BMI (P <0.01). This ratio additionally correlated directly with both the systolic and diastolic blood pressures for the overall patient population (P <0.001). A significant glutathione depletion in the red blood cells resulted in an elevated ratio of oxidized/reduced forms with a reduced antioxidant protective capacity in the hypertensive patients versus the BMI-matched controls (P <0.001). CONCLUSIONS: The presence of systemic oxidative stress was proven in hypertensive children and adolescents, irrespective of their BMI.

Multicentre study of fragrance allergy in Hungary. Immediate and late type reactions.

The authors followed the frequency of fragrance contact sensitization in Hungary in a multicentre study in the years 1998 and 1999. A total of 3,604 patients were tested with fragrance mix (FM), and positive reactions were observed in 294 (8.2%). In 160 FM hypersensitive patients, the study was continued with patch testing of the mix constituents (cinnamic alcohol, cinnamic aldehyde, eugenol, amyl cinnamic aldehyde, hydroxycitronellal, geraniol, isoeugenol, oak moss absolute). Of the patients tested, 70.6% produced positive reactions to the constituents. FM contact sensitization was mainly observed in female patients (74.4%). The incidence of contact urticaria in FM hypersensitive patients was 6.1%. Simultaneous patch test trials of other environmental contact allergens, in both early and late evaluations, mainly confirmed hypersensitivity reactions to balsams. Female dominance of hypersensitivity reactions observed during testing the individual components of the mix was striking (82.4%). In positive skin reactions, cinnamic alcohol, isoeugenol and oak moss provoked skin symptoms most frequently. We also tested the 104 patients who produced negative reactions to FM with the constituent individual allergens, with 11.9% positive incidence. The clinical symptoms of the patients were above all manifest in the form of contact eczema, located on the hands, face, eyelids and axillae. With this study, the authors, members of the Hungarian Contact Dermatitis Research Group, call attention to one of the most frequent allergens in the environment.

Xanthine oxidase activation in mild gestational hypertension.

OBJECTIVE: We hypothesized that activation of the xanthine oxidase (XO) enzyme system is a potential source of free radicals in pregnancy-induced hypertension (PIH). METHODS: A prospective observational study was carried out on 16 pregnant women who met the criteria of gestational hypertension [rise in blood pressure (BP) of 30 mm Hg systolic or 15 mm Hg diastolic after 20 weeks gestation or BP>140/90 mm Hg if earlier pressure is unknown] without proteinuria or any signs of renal impairment. Fourteen women with a clinically normal pregnancy matched for maternal age, parity, and gestational age acted as pregnant controls. Nonpregnant control women were members of the laboratory staff ( n=15). MAIN OUTCOME MEASURES: Concentrations of free sulfhydryl (SH) groups, purine catabolites, lipid peroxidation products in plasma, and blood carboxyhemoglobin levels were used to follow oxidative stress and potential hemolysis. A noninvasive measurement of functional XO activity was carried out (i.e., the urinary ratio of the two metabolites of caffeine was estimated). RESULTS: A pronounced oxidative stress was demonstrated in plasma samples of patients with hypertension by the elevated concentrations of uric acid and lipid peroxidation products. A reduced level of free sulfhydryl groups and an increased concentration of hypoxanthine (HX) were shown in normotensive pregnant individuals. The XO activity index was substantially higher in overweight pregnant subjects with mild hypertension [0.849+/-0.096 ( p<0.01)] than in normotensive pregnant women or in age-matched nonpregnant subjects [0.596+/-0.105, 0.542+/-0.049 (means+/-SD), respectively]. CONCLUSIONS: Our study of mildly hypertensive pregnant subjects provides additional evidence of the putative role of XO activation as a source of free radicals in the early stage of endothelial dysfunction.

Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis in rats.

BACKGROUND: Nontoxic heat shock protein (HSP) inducer compounds open up promising therapeutic possibilities by activating one of the natural and highly conserved defense mechanisms of the organism. AIMS: In the present experiments, we examined the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin-octapeptide (CCK)-induced acute pancreatitis in rats. METHODS: Male Wistar rats weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220 was administered orally, followed by 75 microg/kg CCK subcutaneously three times, after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The animals in group slashed circleB received physiological saline orally instead of BRX-220, but otherwise the protocol was the same as in group B. The rats were exsanguinated through the abdominal aorta 12 h after the last administration of CCK. We determined the serum amylase activity, the plasma trypsinogen activation peptide concentration, the pancreatic weight/body weight ratio, the DNA and total protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree of lipid peroxidation, protein oxidation, and the reduced glutathione level. Histopathological investigation of the pancreas was also performed in all cases. RESULTS: Repeated CCK treatment resulted in the typical laboratory and morphological changes of experimentally induced pancreatitis. The pancreatic levels of HSP60 and HSP72 were significantly increased in the animals treated with BRX-220. In group B, the pancreatic total protein content and the amylase and trypsinogen activities were significantly higher vs. group slashed circleB. The plasma trypsinogen activation peptide concentration, and the pancreatic lipid peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase were significantly decreased in group B vs. group slashed circleB, whereas the glutathione peroxidase activity was increased. The morphological damage in group B was significantly lower than that in group slashed circleB. CONCLUSION: The HSP coinducer BRX-220, administered for 5 d, has a protective effect against CCK-induced acute pancreatitis.