Toxicological effects of thimerosal on rat kidney: a histological and biochemical study / Efeitos toxicológicos do timerosal no rim de rato: um estudo histológico e bioquímico

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

O timerosal é um composto organomercurial, utilizado na preparação de imunoglobulina intramuscular, antivenenos, tintas de tatuagem, antígenos de teste cutâneo, produtos nasais, gotas oftálmicas e vacinas como conservante. Na maioria das espécies animais e nos humanos, o rim é um dos principais locais de deposição de compostos de mercúrio e órgãos-alvo de toxicidade. Assim, a presente pesquisa teve como objetivo avaliar a nefrotoxicidade induzida pelo timerosal em ratos machos. Vinte e quatro ratos albinos machos adultos foram categorizados em quatro grupos. O primeiro grupo era um grupo de controle. Ratos do Grupo II, Grupo III e Grupo IV receberam 0,5µg / kg, 10µg / kg e 50µg / kg de timerosal uma vez ao dia, respectivamente. A administração de timerosal diminuiu significativamente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa redutase (GR), glutationa (GSH) e conteúdo de proteína, enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e peróxido de hidrogênio (H2O2) níveis dependentes da dose. Os níveis de nitrogênio ureico no sangue (BUN), creatinina, urobilinogênio, proteínas urinárias, molécula de lesão renal-1 (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina urinária e a depuração da creatinina foram reduzidas de forma dependente da dose nos grupos tratados com timerosal. Os resultados demonstraram que o timerosal aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappaB (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), níveis de interleucina-6 (IL-6) e atividades da ciclooxigenase-2 (COX-2), DNA e danos histopatológicos dependentes da dose. Portanto, os presentes achados verificaram que o timerosal exerceu nefrotoxicidade em ratos albinos machos.

A Clinical Study Including Patch Test of Rosacea Patients / 대한피부과학회지

BACKGROUND: Rosacea is a relatively common inflammatory skin disease characterized by central facial erythema that persists for several months or longer. Experimental studies have demonstrated that rosacea compromises the epidermal barrier protection against allergens and irritants, rendering rosacea patients susceptible to contact hypersensitivity and skin irritation. OBJECTIVE: This study aimed to investigate allergic and irritant reactions to topical agents and cosmetics in rosacea patients using patch tests. METHODS: Rosacea signs and subtypes of 40 patients were recorded and subjective symptoms and clinical experiences related to topical agents and cosmetics were assessed using a questionnaire. Patch tests were performed in these patients using the Korean Standard Series (Chemotechnique Diagnostics, Sweden), the TRUE test® (Mekos Laboratories ApS, Denmark), and 26 selected fragrance and 31 cosmetic antigens (TROLAB, Germany). RESULTS: Of 40 patch-tested patients, 26 (65%) showed at least 1 positive reaction and 13 (32.5%) showed 2 or more positive reactions. The most common allergens were nickel (II) sulfate (50%), cobalt chloride (10%), epoxy resin (7.7%), and thimerosal (7.5%). Thirteen patients (32.5%) experienced irritant patch test reactions. There were no significant differences in allergic or irritant positive reactions between mild, moderate, and severe cases of rosacea or between rosacea subtypes. Irritant reactions were more common in fair-skinned participants. CONCLUSION: Different topical medications are used in the treatment of rosacea patients. Exacerbation of rosacea may be caused by a hypersensitivity reaction or irritation induced by the topical agent or by cosmetics.

Immunogenicity of a bivalent killed thimerosal-free oral cholera vaccine, Euvichol, in an animal model

PURPOSE: An oral cholera vaccine (OCV), Euvichol, with thimerosal (TM) as preservative, was prequalified by the World Health Organization (WHO) in 2015. In recent years, public health services and regulatory bodies recommended to eliminate TM in vaccines due to theoretical safety concerns. In this study, we examined whether TM-free Euvichol induces comparable immunogenicity to its TM-containing formulation in animal model. MATERIALS AND METHODS: To evaluate and compare the immunogenicity of the two variations of OCV, mice were immunized with TM-free or TM-containing Euvichol twice at 2-week interval by intranasal or oral route. One week after the last immunization, mice were challenged with Vibrio cholerae O1 and daily monitored to examine the protective immunity against cholera infection. In addition, serum samples were obtained from mice to measure vibriocidal activity and vaccine-specific IgG, IgM, and IgA antibodies using vibriocidal assay and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant difference in immunogenicity, including vibriocidal activity and vaccine-specific IgG, IgM, and IgA in serum, was observed between mice groups administered with TM-free and -containing Euvichol, regardless of immunization route. However, intranasally immunized mice elicited higher levels of serum antibodies than those immunized via oral route. Moreover, intranasal immunization completely protected mice against V. cholerae challenge but not oral immunization. There was no significant difference in protection between two Euvichol variations. CONCLUSION: These results suggested that TM-free Euvichol could provide comparable immunogenicity to the WHO prequalified Euvichol containing TM as it was later confirmed in a clinical study. The pulmonary mouse cholera model can be considered useful to examine in vivo the potency of OCVs.

longitudinal cohort study of the D relationship between Thimerosal-containing hepatitis B vaccination and specific delays in development in the United States: Assessment of attributable risk and lifetime care costs

Epidemiological evidence suggests a link between mercury [Hg] exposure from Thimerosal-containing vaccines and specific delays in development. A hypothesis-testing longitudinal cohort study [n = 49,835] using medical records in the vaccine Safety Datalink [VSD] was undertaken to evaluate the relationship between exposure to Hg from Thimerosal-containing hepatitis B vaccines [T-HBVs] administered at specific intervals in the first 6 months of life and specific delays in development [International Classification of Disease, 9th revision [ICD-9]: 315.xx] among children born between 1991 and 1994 and continuously enrolled from birth for at least 5.81 years. Infants receiving increased Hg doses from T-HBVs administered within the first month, the first 2 months, and the first 6 months of life were significantly more likely to be diagnosed with specific delays in development than infants receiving no Hg doses from T-HBVs. During the decade in which T-HBVs were routinely recommended and administered to US infants [1991-2001] an estimated 0.5-1 million additional US children were diagnosed with specific delays in development as a consequence of 25 jig or 37.5jig organic Hg from T-HBVs administered within the first 6 months of life. The resulting lifetime costs to the United States may exceed $1 trillion

Long (27-nucleotides) small inhibitory RNAs targeting E6 protein eradicate effectively the cervical cancer cells harboring human papilloma virus

OBJECTIVE: This study was to identify small inhibitory RNAs (siRNAs) that are effective in inhibiting growth of cervical cancer cell lines harboring human papilloma virus (HPV) and to examine how siRNAs interact with interferon beta (IFN-beta) and thimerosal. METHODS: The HPV18-positive HeLa and C-4I cell lines were used. Four types of siRNAs were designed according to their target (both E6 and E7 vs. E6 only) and sizes (21- vs. 27-nucleotides); Ex-18E6/21, Ex-18E6/27, Sp-18E6/21, and Sp-18E6/27. Each siRNA-transfected cells were cultured with or without IFN-b and thimerosal and their viability was measured. RESULTS: The viabilities of HPV18-positive tumor cells were reduced by 21- and 27-nucleotide siRNAs in proportion to the siRNA concentrations. Of the two types of siRNAs, the 27-nucleotide siRNA constructs showed greater inhibitory efficacy. Sp-18E6 siRNAs, which selectively downregulates E6 protein only, were more effective than the E6- and E7-targeting Ex-18E6 siRNAs. siRNAs and IFN-beta showed the synergistic effect to inhibit HeLa cell survival and the effect was proportional to both siRNA and IFN-beta concentrations. Thimerosal in the presence of siRNA exerted a dose-dependent inhibition of C-4I cell survival. Finally, co-treatment with siRNA, IFN-beta, and thimerosal induced the most profound decrease in the viability of both cell lines. CONCLUSION: Long (27-nucleotides) siRNAs targeting E6-E7 mRNAs effectively reduce the viability of HPV18-positive cervical cancer cells and show the synergistic effect in combination with IFN-b and thimerosal. It is necessary to find the rational design of siRNAs and effective co-factors to eradicate particular cervical cancer.

Prevalencia y causas de ceguera en Perú: encuesta nacional / National survey on the prevalence and causes of blindness in Peru

OBJETIVO: Estimar la prevalencia de ceguera y deficiencia visual en adultos de Perú y precisar sus causas, evaluar la cobertura y la calidad de los servicios de cirugía de catarata y determinar las barreras que impiden acceder a esos servicios. MÉTODOS: Estudio poblacional transversal con muestreo aleatorio por conglomerado en dos pasos de personas de 50 años o más, representativo de todo el país, mediante la metodología estándar de la Evaluación Rápida de Ceguera Evitable. Se midió la agudeza visual y se examinó el cristalino y el polo posterior por oftalmoscopía directa. Se calculó la cobertura de cirugía de catarata y se evaluó su calidad, además de las causas de tener una agudeza visual < 20/60 y las barreras para acceder a ese tratamiento. RESULTADOS:Se examinaron 4 849 personas. La prevalencia de ceguera fue 2,0% (intervalo de confianza de 95%: 1,5-2,5%). La catarata fue la causa principal de ceguera (58,0%), seguida por el glaucoma (13,7%) y la degeneración macular relacionada con la edad (11,5%). Los errores de refracción no corregidos fueron la principal causa de deficiencia visual moderada (67,2%). La cobertura de cirugía de catarata fue de 66,9%, y 60,5% de los ojos operados de catarata logró una AV ≥ 20/60 con la corrección disponible. Las principales barreras para someterse a la cirugía de catarata fueron el alto costo (25,9%) y no saber que el tratamiento es posible (23,8%). CONCLUSIONES: La prevalencia de ceguera y deficiencia visual en Perú es similar a la de otros países latinoamericanos. La baja cobertura de cirugía de catarata y el envejecimiento poblacional indican que para aumentar el acceso a estos servicios se debe mejorar la educación de la población en salud ocular y la capacidad resolutiva de los servicios oftalmológicos y de cirugía de catarata, y reducir su costo.

OBJECTIVE: To estimate the prevalence of blindness and visual impairment among adults in Peru and to determine their causes, to evaluate the coverage and quality of the cataract surgical services and to investigate the barriers that inhibit access to these services. METHODS: A cross-sectional population study with two-stage random cluster sampling of individuals of ≥ 50 years old, representative of the entire country, using the standard methodology of the Rapid Assessment of Avoidable Blindness. Visual acuity was assessed and the condition of the lens and posterior pole examined by direct ophthalmoscopy. Cataract surgical coverage was calculated. Its quality, as well as the causes of visual acuity < 20/60 and the barriers to accessing surgical treatment were assessed. RESULTS: A total of 4 849 people were examined. Blindness prevalence was 2.0% (confidence interval of 95%: 1.5-2.5%). The main causes of blindness were cataract (58.0%), glaucoma (13.7%) and age-related macular degeneration (11.5%). Uncorrected refraction errors were the principal cause of moderate visual impairment (67.2%). Cataract surgical coverage was 66.9%. 60.5% of the eyes operated for cataracts achieved a visual acuity ≥ 20/60 with available correction. The main barriers to cataract surgery were the high cost (25.9%) and people being unaware that treatment was possible (23.8%). CONCLUSIONS: The prevalence of blindness and visual impairment in Peru is similar to that of other Latin American countries. Given the low cataract surgical coverage and the aging of the population, access to the services could be improved by increasing the population education on eye health and the response capacity of the ophthalmological and cataract surgical services, and by reducing the costs of the latter.

O uso de Timerosal em vacinas, as implicações para o Programa Nacional de Imunizações Brasileiro e a nova Convenção de Minamata sobre o mercúrio / The use of Thimerosal in vaccines, the implications for the Brazilian National Immunization Program and the new Minamata Convention on Mercury

Este trabalho teve por objetivo contextualizar a discussão em relação ao uso de Timerosal em Vacinas e suas implicações para a saúde das pessoas, tendo em vista a discussão no Conselho de Ministros do Programa das Nações Unidas para o Meio Ambiente (PNUMA), onde se montou um Grupo de Trabalho para o estabelecimento de uma Convenção com o objetivo de banir o metal mercúrio e seus subprodutos do uso cotidiano, como forma de reduzir a exposição antrópica e a toxidade desse elemento em todas as cadeias humanas de produção. Nesse processo de discussão, com a participação dos Países Partes do PNUMA, da sociedade civil internacional,da academia, de outros Órgãos das Nações Unidas - a exemplo da Organização Mundial da Saúde (OMS) - e da indústria, foi concretizada a Convenção de Minamata para o Mercúrio. Esse trabalho reflete as participações do pesquisador nos encontros entre os Países e inúmeras outras reuniões entre os grupos de contato, onde participou como delegado do Ministério da Saúde.Trabalhos de pesquisa, onde o pesquisador é ator participante da discussão e de seus ensinamentos, permitem uma visão do contexto da criação da normatização que tem utilidade no contexto de Políticas Públicas para o Setor Saúde.

This study aimed to contextualize the discussion regarding the use of Thimerosal in vaccines and their implications for human health, in view of the discussion in the Council of Ministers of the United Nations Environment Programme (UNEP), where a Working Group was set for the establishment of a Convention with the purpose of banning mercury and by products of every day use, as a way to reduce anthropogenic exposure and toxicity of this element in all human production chains. The Minamata Convention on Mercury is the result of a process of discussion, with the participation of UNEP Country Parties, international civil society, academia, other United Nations bodies - such as the World Health Organization (WHO) - and industry. This work reflects the participation of the researcher, as delegate of the Ministry of Health, to the meetings of the Working Groups, and all other ones held by contact groups, and its learning, which made possible to be inside the context of the creation of norms, which is useful to a better understanding of Public Policies for the Health Sector.

Timerosal en las vacunas: ¿blanco, negro, o más bien todo lo contrario? / Thimerosal in vaccines: white, black, or quite the opposite?

El presente artículo tiene por objetivo analizar la controversia ocurrida en Chile, especialmente durante los últimos meses, en relación a un proyecto de ley que busca prohibir la fabricación, importación, comercialización o distribución de vacunas que contengan dentro de sus compuestos, en cualquier nivel de concentración, timerosal o compuestos organomercúricos. Sin constituir una síntesis formal de toda la investigación existente, se analiza la evidencia científica que los distintos actores han utilizado, las razones de la controversia y las anomalías en el proceso de toma de decisión sanitaria.

This article analyzes the recent controversy regarding the introduction of a bill to Chilean Congress that aims to ban thiomersal and/or any trace of organomercurial compounds from vaccines in the country. Rather than providing a formal overview of all available evidence, this analysis focuses on the reasons behind the controversy, the scientific evidence invoked by both sides in the debate, and the anomalies in the healthcare decision-making process.

J'accuse desde la bioética: análisis de la discusión sobre el timerosal en Chile / A bioethical j’accuse: analysis of the discussion around thiomersal in Chile

El Poder Legislativo chileno propone una ley que elimine el timerosal como preservante de las vacunas parenterales del Programa Nacional de Inmunizaciones, proyecto que el Poder Ejecutivo se ha propuesto vetar. El mundo científico informa mayoritariamente que la sospecha de neurotoxicidad atribuida al timerosal es infundada. Pese a ello, las autoridades médicas han oscilado entre sostener que la precaución sugiere apoyar la ley y en otros momentos han manifestando que es más precautorio mantener los programas de vacunación actualmente vigentes. Estas contradicciones y oposiciones ilustran que materias que conciernen a la ciudadanía, requieren una reflexión bioética acabada sobre las políticas públicas sanitarias. Han quedado claro las deficiencias de la deliberación política y la falta de participación social en decisiones que, dado el grado de incertidumbre involucrada en temas como inmunización, requieren no sólo la inclusión de la ciudadanía sino el respeto de la autonomía individual para aceptar o rechazar la inclusión en los programas de vacunación propuestos por las políticas sanitarias. La participación ciudadana en nuestro país se ve severamente limitada por la falta de instrumentos sociales como el plebiscito, el ombudsman y, especialmente, la desidia en crear la Comisión Nacional de Bioética exigida por la Ley 20.120 de 2006, una de cuyas funciones más importantes es mediar deliberativamente entre legos, expertos y políticos en la generación de políticas sanitarias legitimadas por la participación ciudadana.

Chilean legislators have voted to ban vaccines preserved with thiomersal, an initiative that the Executive has vetoed. Most scientific evidence has dismissed the alleged toxicity of this substance, in accordance with the formal and publicly expressed opinion of local experts, and yet, medical authorities have issued contradictory statements. Some have argued that the principle of precaution suggests eliminating thiomersal preserved vaccines; others have declared that current vaccines should be maintained to protect the population. From the perspective of bioethics, this polemic is another example of the shortcoming of the deliberation process leading to controversial laws in lieu of including citizens in the discussion of regulations that harbor uncertainties, and respect for individual autonomy to accept or reject public immunization programs. The Chilean legal system has been unwilling to implement participatory democratic procedures like plebiscites or institutions such as the ombudsman. In 2006 a law was enacted that creates a National Commission of Bioethics, but successive governments have failed to create such a commission, which is an efficient social instrument to conduct deliberation on bioethical issues that require a balanced participation of the public, experts, and politicians.

La evidencia acerca de la controversia de las vacunas que contienen timerosal y su asociación con el autismo / Addressing the controversy regarding the association between thimerosal-containing vaccines and autism

La vacunación es una de las medidas de mayor impacto en la salud pública para la reducción de la morbimortalidad infantil. El timerosal es un compuesto orgánico del mercurio utilizado como preservante de los frascos multidosis. Eventualmente, en el Perú, surgen olas de controversia acerca de la seguridad de estas vacunas, asociándolas especialmente con el autismo. Como resultado de estas controversias, se han propuesto, incluso, leyes que prohíben este tipo de vacunas, lo que tendría un importante impacto en los costos y en los aspectos logísticos de la estrategia nacional de vacunación. En este artículo se revisa la literatura sobre las principales controversias acerca de las vacunas que contienen timerosal y su supuesta asociación con el autismo. Se realiza una aproximación histórica sobre estas controversias, se hace una actualización de la evidencia científica disponible al momento, y se revisa la posición de los organismos internacionales más importantes con respecto a este tema. Se concluye que la evidencia científica no apoya la noción que exista una asociación entre el uso del timerosal en las vacunas con los trastornos del espectro autista en niños.

Vaccination is one of the most important public health interventions in the reduction childhood morbidity and mortality. Thimerosal is an organic mercury compound used as preservante in multi-dose vials. Often in Peru, there are waves of controversy about the safety of this type of vaccines, mainly arguing that there is an association between them and autism. As a result of these controversies, there have been some voices asking for laws banning thimerosal-containing vaccines, which would have a large impact in costs and the logistic aspects of the public vaccination programs. The aim of this article is to review the literature for the main controversies about thimerosal in vaccines and its supposed association to autism. We made an historical review about these controversies given the available scientific evidence and the statements from important international organizations. We concluded that the current available evidence do not support an association between thimerosal and childhood neurodevelopmental disorders, such as autism.

Patch Test (T.R.U.E. Test) Results in Patients with Allergic Contact Dermatitis: 2007~2011, Chungcheongnamdo / 대한피부과학회지

BACKGROUND: A number of skin manifestations in patients with allergic contact dermatitis result from sensitization with specific allergens, and patch testing is used as a diagnostic means of identifying theses allergens. In Korea, the commercial patch test panel, the TRUE-test, has been available since 2005. However, there have been few reports regarding the results of the TRUE-test. OBJECTIVE: The purpose of this study was to analyze the type, frequency, and changes in common contact allergens in Korea using the TRUE test. METHODS: A total of 311 patients with allergic contact dermatitis were evaluated by the TRUE test between January 2007 and December 2011 at Soonchunhyang hospital. Patch test reading was performed on day 2 and day 4. RESULTS: A total of 311 cases of TRUE test records (male 79, female 232) were compiled and analyzed. The highest age distribution was the 4th decade in females. The face, with exception of the lips, was the most frequently affected site (40.2%). Overall, 58.8% of patients had at least on positive reaction, and the most common allergens were nickel sulfate (31.8%), p-phenylenediamine (13.5%), cobalt chloride (10.0%), thiomersal (7.4%), and carba mix (5.5%). Nickel allergen displayed higher positive rates than the rates in other countries. CONCLUSION: There was no significant difference in the overall positive rate of patch test results compared with recent studies. However, we confirmed that metal-related allergens remain the most common, and that the results provide the basis for the use of the TRUE test in patients with contact dermatitis in Korea.

A Study of Patch Test Results in Patients with Facial Dermatitis / 대한피부과학회지

BACKGROUND: Patch test is usually performed in order to differentiate allergic contact dermatitis from other facial skin diseases; however, there are only infrequent comparative studies regarding the positive allergens patch tested between allergic contact dermatitis and other facial skin diseases. OBJECTIVE: The purpose of this study was to investigate the positivity of patch test in patients with facial dermatitis and to analyze the valid positive allergen patch tested in allergic contact dermatitis compared to other facial skin diseases. In addition, we evaluated the difference of positive allergen according to clinical features, such as age, sex, site of the lesion and duration of disease, in patients with allergic contact dermatitis. METHODS: A total of 409 patients tested with facial dermatitis patch were retrospectively reviewed for medical recordings, including clinical features, occupational history, clinical photos and the results of a Korean standard series of patch tests. RESULTS: Compared with other facial skin disease, patients diagnosed with allergic contact dermatitis showed higher rate in the patch test, responding to 2 or more allergens. They also had more statistically valid positive allergens, such as phenylendiamine base, cobalt, colophony, thimerosal and isothizolinone. In addition, there were a few allergens which revealed significant differences in the positivity of the patch test according to the clinical features in patients diagnosed with allergic contact dermatitis. CONCLUSION: Based on these results, we could receive help in order to classify the positive allergens as relevant allergens in the patch test for the differentiation of allergic contact dermatitis from other facial skin disease.

A Study on Anlaysis of Patch Test Positive Reactivity according to the Reading Time with T.R.U.E. TEST(R) / 대한피부과학회지

BACKGROUND: The patch test is widely used for diagnosis of allergic contact dermatitis. However, nearly half of positive reactions can be observed only on day 2 or day 4 and it is difficult to interpret these reactions. OBJECTIVE: The purpose of this study is to assess the frequency of transient and delayed reactions in TRUE-test and detect common antigens that provoke these reactions. METHODS: A total of 311 patients with allergic contact dermatitis were evaluated by TRUE-test between Jan 2007 and December 2011. Records of patch test results of day 2 and day 4 were reviewed and analyzed. RESULTS: A total 311 cases of T.R.U.E. TEST(R) records (male 79, female 232) were analyzed. Persistent reactions were observed in 80.1% patients tested, transient reactions were observed in 18.3%, and delayed reaction in 5%. Frequent allergens which showed transient reactions were cobalt dichloride (2.9%), nickel sulfate (2.2%), thiomersal (1.9%), and carba mix (1.6%), in order of frequency. Allergens which showed delayed reactions were nickel sulfate (0.3%), fragrance mix (0.3%), p-tert-butylphenol formaldehyde resin (0.43). CONCLUSION: Our results showed a relatively high frequency of transient reaction in T.R.U.E. TEST(R). This suggests that additional reading at day 4 in the patch test would be of value.

Active Sensitization of Para-tertiary-butylphenol after TRUE Test(R) / 대한피부과학회지

Active sensitization of contact allergen is an uncommon complication of patch test. Para-tertiary-butylphenol (PTBP) is a component of neoprene-based adhesives used in glued leather goods such as shoes, handbags, belts and watchstraps. Contact allergy to PTBP is frequently seen when the patch test is performed. However, active sensitization to PTBP after the patch test is rare. A 23-year-old female patient came to our clinic with a brownish hyperpigmented patch on the belt position of her belly. Pruritic erythematous papules and vesicles developed on the abdomen when she wore new pants 4 months ago. Under the clinical diagnosis of allergic contact dermatitis, the patient was patch tested with the Thin-layer Rapid Use Epicutaneous Test (TRUE Test(R)). The result showed strong positive reaction to nickel sulphate and thiomersal both on day 2 and 3 after application. Twenty-nine days after the test, the patient noticed pruritus on the TRUE Test(R) area. Thirty-four days after the test, an erythematous square-shaped plaque studded with tiny vesicles developed at the PTBP patch test site. This strongly suggests that the reaction to PTBP is occurred. She was diagnosed with an active sensitization to PTBP. We report a rare and interesting case of active sensitization to PTBP after TRUE Test(R).

Mercury Promotes Catecholamines Which Potentiate Mercurial Autoimmunity and Vasodilation: Implications for Inositol 1,4,5-Triphosphate 3-Kinase C Susceptibility in Kawasaki Syndrome

Previously, we reviewed biological evidence that mercury could induce autoimmunity and coronary arterial wall relaxation as observed in Kawasaki syndrome (KS) through its effects on calcium signaling, and that inositol 1,4,5-triphosphate 3-kinase C (ITPKC) susceptibility in KS would predispose patients to mercury by increasing Ca2+ release. Hg2+ sensitizes inositol 1,4,5-triphosphate (IP3) receptors at low doses, which release Ca2+ from intracellular stores in the sarcoplasmic reticulum, resulting in delayed, repetitive calcium influx. ITPKC prevents IP3 from triggering IP3 receptors to release calcium by converting IP3 to inositol 1,3,4,5-tetrakisphosphate. Defective IP3 phosphorylation resulting from reduced genetic expressions of ITPKC in KS would promote IP3, which increases Ca2+ release. Hg2+ increases catecholamine levels through the inhibition of S-adenosylmethionine and subsequently catechol-O-methyltransferase (COMT), while a single nucleotide polymorphism of the COMT gene (rs769224) was recently found to be significantly associated with the development of coronary artery lesions in KS. Accumulation of norepinephrine or epinephrine would potentiate Hg2+-induced calcium influx by increasing IP3 production and increasing the permeability of cardiac sarcolemma to Ca2+. Norepinephrine and epinephrine also promote the secretion of atrial natriuretic peptide, a potent vasodilator that suppresses the release of vasoconstrictors. Elevated catecholamine levels can induce hypertension and tachycardia, while increased arterial pressure and a rapid heart rate would promote arterial vasodilation and subsequent fatal thromboses, particularly in tandem. Genetic risk factors may explain why only a susceptible subset of children develops KS although mercury exposure from methylmercury in fish or thimerosal in pediatric vaccines is nearly ubiquitous. During the infantile acrodynia epidemic, only 1 in 500 children developed acrodynia whereas mercury exposure was very common due to the use of teething powders. This hypothesis mirrors the leading theory for KS in which a widespread infection only induces KS in susceptible children. Acrodynia can mimic the clinical picture of KS, leading to its inclusion in the differential diagnosis for KS. Catecholamine levels are often elevated in acrodynia and may also play a role in KS. We conclude that KS may be the acute febrile form of acrodynia.