2-Cyanoethyl dimethyldithiocarbamate, a new contact allergen found in accelerator-free nitrile gloves.

BACKGROUND: Allergic contact dermatitis (ACD) from rubber glove usage is usually caused by rubber additives such as the accelerators. However, in analyses of the suspected gloves, ordinary rubber allergens are not always found. Accelerator-free rubber gloves are available, but some patients with accelerator allergy do not tolerate them and might also be patch test positive to them. OBJECTIVES: To identify and chemically characterize a new allergen, 2-cyanoethyl dimethyldithiocarbamate (CEDMC), in rubber gloves. We describe two patient cases: patient 1 that led us to the identification of CEDMC and patient 2 with occupational ACD caused by CEDMC. METHODS: The patients were examined with patch testing including baseline and rubber series, and their own rubber gloves. High-performance liquid chromatography (HPLC) was used for chemical analysis of rubber gloves. The allergen was synthesized and identified by nuclear magnetic resonance, mass spectrometry and infrared spectrometry, and tested on patient 2. RESULTS: CEDMC was identified by HPLC in a nitrile glove associated with hand eczema in patient 1. Patient 2 whose nitrile gloves contained CEDMC was patch test positive to CEDMC. CONCLUSIONS: CEDMC is a new contact allergen in nitrile gloves and probably forms during vulcanization from residual monomer acrylonitrile and rubber additives.

Positive Patch Test Reactions to Carba Mix and Thiuram Mix: The North American Contact Dermatitis Group Experience (1994-2016).

BACKGROUND/OBJECTIVE: This study characterizes concomitant reactions to carba mix (CM) and thiuram mix (TM) in a large North American population. Because thiurams and dithiocarbamates have structural similarity, concomitant reactions are expected. METHODS: The 1994-2016 North American Contact Dermatitis Group data were analyzed. Patients with a final reaction interpreted as "allergic" to either CM or TM were included. RESULTS: A total of 49,758 patients were tested to both CM and TM. A total of 3437 (6.9%) had positive reactions to CM and/or TM including the following groups: CM+ only (n = 1403, 40.8%), TM+ only (n = 1068, 31.0%), or both (n = 966, 28.1%). A total of 47.5% of TM+ patients were positive to CM and 40.8% of CM+ patients were positive to TM. Male sex, occupationally related dermatitis, and hand involvement were significantly more common in individuals positive to CM and/or TM as compared with those who were negative (P < 0.0001). More than 80% of CM+/TM+ reactions were currently relevant. Gloves were the most common source of CM and TM; clothing and footwear were also frequent. CONCLUSIONS: Carba mix and TM remain important, clinically relevant allergens. Although significant concomitant reaction frequency was demonstrated, more than half of the patients reacting to either CM or TM would have been missed if both had not been tested, underscoring the importance of testing to both.

Patch Testing to Diphenylguanidine by the North American Contact Dermatitis Group (2013-2016).

BACKGROUND/OBJECTIVES: Carba mix (CM, 3% petrolatum) contains 1,3-diphenylguanidine (DPG, 1%), zinc diethyldithiocarbamate (1%), and zinc dibutyldithiocarbamate (1%). Because DPG is a component of CM, DPG is often not tested separately. The purpose of this study was to determine the frequency of concomitant reactions to CM and DPG. METHODS: A retrospective analysis of the 2013-2016 North American Contact Dermatitis Group data was conducted. The study group consisted of patients with final interpretation of "allergic" to either DPG or CM. Reactions coded as irritant or doubtful/macular erythema (+/- and not interpreted as allergic) were excluded. RESULTS: A total of 10,457 patients were patch tested to both CM and DPG, and 610 (5.8%) had allergic reactions to either CM or DPG (CM only [n = 292, 47.9%], DPG only [n = 190, 31.1%], both [n = 128, 21.0%]). A total of 39.4% of CM-allergic patients reacted to DPG, and 59.7% of DPG-allergic patients reacted to CM. Analyses found that 25% (++/+++ subgroup) to 40% (all patients) of allergic reactions to DPG would have been missed by testing to CM alone. More than 70% of reactions to CM and DPG were +/- or +. CONCLUSIONS: Patch testing to CM will miss 25% to 40% of positive reactions to DPG. Both CM and DPG have a high frequency of +/- and + reactions.

Allergic contact dermatitis caused by synthetic rubber gloves in healthcare workers: Sensitization to 1,3-diphenylguanidine is common.

BACKGROUND: The frequency of allergic contact dermatitis has significantly increased in healthcare workers since the transition from latex to synthetic rubber gloves, with 1,3-diphenylguanidine being identified as the most frequently implicated allergen. OBJECTIVES: To highlight the role of 1,3-diphenylguanidine as the culprit allergen in contact allergies to synthetic rubber gloves, to propose recommendations for patch testing, and to discuss alternatives for sensitized subjects. MATERIALS AND METHODS: Patch test data from healthcare workers who developed hand dermatitis after wearing rubber gloves and who reacted positively to glove samples and rubber additives were collected from September 2010 to December 2017 in a Belgian hospital. RESULTS: A total of 44 caregivers were included in this study. Patch tests showed that: (a) 84% of the study population reacted positively to carba mix; (b) 86% reacted positively to 1,3-diphenylguanidine; and (c) 13 (30%) reacted positively to thiuram mix. Half of the subjects reacted positively to gloves containing 1,3-diphenylguanidine, whereas none reacted to accelerator-free gloves. CONCLUSION: The most commonly identified allergen was 1,3-diphenylguanidine, far ahead of thiurams, which were previously described as the most sensitizing accelerators. The use of 1,3-diphenylguanidine-free gloves is recommended. No subject reacted to gloves without accelerators, thus confirming their efficiency among accelerator-sensitized patients. We recommend that 1,3-diphenylguanidine be added to the European baseline series.

Occupational contact sensitization in female geriatric nurses: Data of the Information Network of Departments of Dermatology (IVDK) 2005-2014.

BACKGROUND: Geriatric nurses (GN) have a high risk of occupational contact dermatitis (OCD), with chronic irritant contact dermatitis predominating. However, allergic contact dermatitis is an important issue as well. Little is known whether the relevant occupational allergen spectrum reported in the 1990s, including fragrances, preservatives, rubber chemicals and ingredients of surface disinfectants to be the most common sensitizers in GN, is still valid. OBJECTIVES: To monitor the current allergen spectrum in GN with OCD and verify the validity of the patch test recommendations (baseline-, preservative-, ointment base-, rubber-, disinfectant, series and fragrances) in GN with suspected OCD given by the German Contact Dermatitis Research Group (DKG). METHODS: Retrospective analysis of IVDK data (2005-2014) of 743 female GN with OCD, in comparison to 695 GN without OCD. RESULTS: GN with OCD reacted significantly more frequently to both fragrance mixes, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC), thiuram mix, zinc diethyldithiocarbamate and mercaptobenzothiazole than GN without OCD. Reactions to MDBGN, methylchloroisothiazolinone/methylisothiazolinone and oil of turpentine occurred substantially, but not significantly more frequently among GN with OCD. The latter may be due to former use of a special alcoholic liniment in geriatric care. Among material from the patients' workplaces, tetrazepam was a frequent allergen, due to dust exposure from pill crushing. Furthermore, occupationally used protective gloves, body care products as well as surface disinfectants were often tested positively. CONCLUSIONS: The general allergen spectrum in GN with OCD is unchanged, so the DKG patch test recommendations are still valid. Prevention of occupational sensitization should focus on fragrance-free hygiene and body care products, usage of accelerator-free protective gloves and avoidance of drug dust exposure.

Ammonium salts of carbamodithioic acid as potent vaginal trichomonacides and fungicides.

Chemical attenuation of the reactive oxygen species (ROS)-sensitive anaerobes Trichomonas vaginalis, which is the most prevalent non-viral sexually transmitted infection, and two often coexisting vaginal infections, namely Candida albicans and Staphylococcus aureus, which are opportunistic reproductive tract infections, was attempted with novel ammonium salts of carbamodithioic acid through inhibition of free thiols. In vitro and in vivo efficacies of the designed compounds were evaluated as topical vaginal microbicides. Five compounds showed exceptional activity against drug-resistant and -susceptible strains with negligible toxicity to host (HeLa) cells in vitro in comparison with the standard vaginal microbicide nonoxynol-9 (N-9), without disturbing the normal vaginal flora (i.e. Lactobacillus). The compounds significantly inhibited the cytopathic effects of Trichomonas on HeLa cells in vitro with efficacies comparable with metronidazole (MTZ); however, their efficacy to rescue host cells from co-infection (protozoal and fungal) was greater than that of MTZ. The compounds inhibited ß-haemolysis of red blood cells caused by Trichomonas and were found to be active in vivo in the mouse subcutaneous abscess assay. Some compounds rapidly immobilized human sperm. A mechanism involving inhibition of free thiols and consequently the cysteine proteases of T. vaginalis by the new compounds has been proposed. Thus, a unique scaffold of antimicrobial agents has been discovered that warrants further investigation for development as contraceptive vaginal microbicides.

ESSCA results with the baseline series, 2009-2012: rubber allergens.

BACKGROUND: Allergic contact dermatitis caused by rubber allergens is common, and causes significant patient morbidity. Contemporary data are important to allow appropriate preventive measures and identification of contact allergy trends. OBJECTIVES: To describe the pattern of patch test reactivity to rubber allergens, including those in the European baseline series. METHODS: Data collected by the European Surveillance System on Contact Allergies (ESSCA) network between 2009 and 2012 from 12 European countries were analysed. RESULTS: Contact allergy to thiuram mix declined over the studied time period, with an overall prevalence of 1.87%. The prevalence of allergy to carba mix was 2.29%, and was significantly increasing. Prevalence rates of sensitization to other rubber allergens were largely unchanged. Statistical analysis with the MOAHLFA index confirmed the strong links between rubber allergy and occupational hand dermatitis. CONCLUSIONS: Changing patterns of allergy to rubber additives have been identified. Inclusion of carba mix in the European baseline series may be appropriate.

UK rates of occupational skin disease attributed to rubber accelerators, 1996-2012.

BACKGROUND: Natural and synthetic rubbers containing rubber accelerators are well-known causes of allergic contact dermatitis (ACD). Latex contact urticaria (CU) has been widely reported, especially when powdered latex glove use was commonplace. Consequently, interventions to reduce latex exposure by altering glove manufacture were introduced. OBJECTIVE: This study aimed to analyse trends in UK-reported incidence of occupational skin disease associated with rubber accelerators. METHOD: We analysed cases reported to EPIDERM (part of The Health and Occupation Research network) of occupational ACD caused by natural and synthetic rubber products, between 1996 and 2012. RESULTS: For the studied period, a decreasing incidence of ACD associated with rubber products was found, with an average annual change of -1.2% [95% confidence interval (CI) -3.1 to 0.7]. The number of cases of latex CU (n = 580) significantly declined. The number of cases of ACD caused by mercapto mix and mercaptobenzothiazole (n = 177) and thiuram mix (n = 603) also declined. Reports of ACD associated with carba mix and its constituents (n = 219) increased significantly, by an average annual percentage of 10.1% (95%CI: 6.1-14.2). Twenty-six cases of ACD caused by rarer rubber compounds were identified, highlighting skin disease attributable to less widely recognized chemicals. CONCLUSIONS: These data show a falling reported incidence of occupational ACD attributed to rubber chemicals, but within this a significant rise attributable to the constituents of the carba mix. Clinicians should recognize the changing diversity of chemicals used in rubber manufacturing, and consider including carba mix in their baseline series and testing beyond this in suspect cases to avoid false-negative results.

Positive patch test reactions to carba mix and iodopropynyl butylcarbamate: data from the North American Contact Dermatitis Group, 1998-2008.

BACKGROUND: Carba mix (CM) contains 3 chemicals used as accelerators in manufacturing of rubber products and agricultural chemicals. Iodopropynyl butylcarbamate (IPBC) is a preservative used in industrial and personal care products. Potential cross-reactivity between these allergens is unclear. OBJECTIVE: This study aimed to determine concomitant reaction rates between CM (3% petrolatum [pet]) and IPBC (0.1% pet and/or 0.5% pet). DESIGN: A retrospective cross-sectional analysis of data from the North American Contact Dermatitis Group from 1998 to 2008 was conducted. Frequencies of positive reactions, strength of reactions, and concomitant reaction rates were calculated. RESULTS: A total of 25,435 patients were tested. There were 1131 allergic reactions to CM and 346 positive reactions to IPBC (either 0.1% pet and/or 0.5% pet). Fifty-two patients reacted to both allergens. Most reactions (>69%) were doubtful/weakly positive, and of those who reacted to both, most (58%) had doubtful and/or weakly positive reactions. There was a statistically significant association of concomitant reactions between CM and IPBC; formaldehyde positivity was used as control and showed statistically significant concomitant reactions. CONCLUSIONS: Overall, concomitant reactions to CM and IPBC were low, and rates varied by strength of reaction. True cross-reactivity is unlikely; statistical association is likely due to frequent low-grade reactions to irritant patch test preparations.

Purification and partial characterization of oxalate oxidase from leaves of forage Sorghum (Sorghum vulgare var. KH-105) seedlings.

An oxalate oxidase was purified to apparent homogeneity from the leaves of 10-days old seedlings of forage Sorghum (Sorghum vulgare var. KH-105). The enzyme had a Mr of 124 kDa with two identical subunits, an optimum pH of 4.5, optimum temperature of 37 degrees C and activation energy (Ea) of 2.0338 Kcal/mol. The rate of reaction was linear up to 7 min. K(m) value for oxalate was 0.22 mM. The enzyme was stimulated by Cu2+ and inhibited by EDTA, NaCN, diethyldithiocarbamate, Na2SO4, but unaffected by NaCl at 0.1 mM concentration. Although the enzyme was stimulated by flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), UV and visible spectra of the enzyme did not match with that of a flavoprotein. The positive reaction of the enzyme with orcinol-H2SO4 reagent indicated its glycoprotein nature. The superiority of the purified enzyme over earlier reported oxalate oxidases for determination of urinary oxalate has been demonstrated.

Soccer shin guard reactions: allergic and irritant reactions.

In spite of the worldwide popularity of soccer among youth and the common requirement of the use of protective shin guards, reports of allergy to shin guards is sparse. This is surprising in light of the fact that this equipment is often made of materials that are reported to cause allergies, and that friction and moisture from the use of these shin guards during the sport would seem to predispose soccer players to the development of an allergic response. We present eight patients that presented for evaluation of dermatitis under their shin guards--some of which had allergy to their shin guards and some of which were diagnosed as having an irritant reaction.

Avaliação in vitro de fármacos pró-oxidantes sobre o Schistosoma mansoni / In vitro evaluation of drugs pro-oxidants on Schistosoma mansoni

Segundo a Organização Mundial de Saúde (2002), a esquistossomose é a segunda maior doença tropical, causadora de 200 a 300 mil mortes por ano. Mesmo apresentando alguns quimioterápicos eficazes para o tratamento, como o praziquantel (PZQ) e a oxamniquina (OXQ), ocorrem muitos casos refratários e efeitos colaterais. Diante deste contexto, é necessária a busca racional de novos medicamentos e combinações para o tratamento desta doença. Uma possível solução é o estudo de drogas relacionadas com o estresse oxidativo do patógeno. Dentre estas podem ser analisadas: a artemisinina (ART) , que induz uma maior produção de radicais livres por inibição da formação da hemozoína em Plasmodium falciparum; a butionina sulfoximina (850), que impede a produção da glutationa; além do dietilditiocarbamato de sódio (DDC), que age como inibidor das superóxido dismutases. Portanto, o objetivo deste trabalho foi testar in vitro essas drogas, isoladas e combinadas, analisando a atividade das superóxido dismutases, alterações morfológicas e produção de hemozoína em vermes adultos, além de avaliar a toxicidade em esplenócitos. A ART apresentou efeito esquistossomicida em concentrações elevadas. O DDC mostrou um efeito esquistossomicida satifatório e inibiu as superóxido dismutases. Quanto à associação ART - DDC, esta inibiu a formação da hemozoína, apresentou danos nos tegumentos dos vermes e não apresentou citotoxicidade significativa. Estes resultados indicam que estas drogas são viáveis para estudos in vivo, podendo ser uma nova alternativa quimioterápica para esta patologia.

Zinc diethyldithiocarbamate allergenicity: potential haptenation mechanisms.

BACKGROUND: Zinc diethyldithiocarbamate (ZDEC) and its disulfide, tetraethylthiuram disulfide (TETD), are rubber accelerators and contact allergens that cross-react in some individuals. OBJECTIVE: This study explored potential protein haptenation mechanisms of ZDEC and its oxidation products. METHODS: ZDEC oxidation/reduction products and sites of protein binding were assessed using high-performance liquid chromatography and mass spectrometry. The murine local lymph node assay (LLNA) was employed to probe haptenation mechanisms of ZDEC by examining its allergenicity along with its oxidation products and through elimination of oxidation and chelation mechanisms by substituting cobalt for zinc [cobalt (II) dithiocarbamate, CoDEC]. RESULTS: Oxidation of ZDEC by hypochlorous acid (bleach, HOCl), iodine, or hydrogen peroxide resulted in production of TETD, tetraethylthiocarbamoyl disulfide, and tetraethyldicarbamoyl disulfide (TEDCD). Albumin thiols reduced TETD with subsequent mixed disulfide formation/haptenation. ZDEC directly chelated the copper ion on the active site of the superoxide dismutase, whereas CoDEC did not bind to Cu proteins or form mixed disulfides with free thiols. ZDEC, sodium diethyldithiocarbamate, TEDCD, and TETD were all positive in the LLNA except CoDEC, which was non-allergenic. CONCLUSION: The thiol is the critical functional group in ZDEC's allergenicity, and haptenation is predominantly through chelation of metalloproteins and formation of mixed disulfides.

[AIDS: ethics and scientific investigation on human beings]. / Sida: éthique et investigation scientifique sur l'être humain.

The experimentation on human beings of one or several therapeutic molecules discovered in laboratory is necessary and important because it helps to find new treatments or new diagnostic methods. But, it presents serious ethical problems. In this article we are analysing the example of the HIV infection. We are succinctly describing the research methods in laboratory for therapeutic molecules, first the experimentation on animals and then on human being in clinical trials. We will then try to show, with several examples, how during these last 25 years of HIV infection, the research of new molecules has not always respected the ethical rules set out in Helsinki declaration, "Code de la santé publique" or "Guide de bonnes pratiques cliniques-ICH" etc. We are discussing here the way to avoid these irregularities.

Contact allergy to p-tert-butylphenol formaldehyde resin and zinc diethyldithiocarbamate in a wet suit.

Rubber materials are common causes of contact dermatitis. Neoprene is a special synthetic rubber used in many products (eg, wet suits, elastic supports, gloves, shoes, and orthopedic devices). A 31-year-old man was admitted to our dermatoallergologic clinic with the development of a generalized itching erythematovesicular eruption. He reported that clinical manifestations occurred after he wore a neoprene wet suit that he was used to wearing for water sports. Although allergic contact dermatitis from a wet suit is not uncommon, it is usually due to thiourea derivatives whereas our patient presented with contact allergy to p-tert-butylphenol formaldehyde resin and zinc diethyldithiocarbamate.