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BACKGROUND: Aquagenic keratoderma is triggered in the palms and soles after contact with water, and is characterized by the appearance of translucent papules forming macerated plaques. It may be associated with medications and diseases such as cystic fibrosis, atopy, and malnutrition, or be idiopathic. CASE REPORT: We describe the case of a 17-year-old female patient with chronic functional abdominal pain. She presented with a 2-month history of "wrinkling" of palms after contact with water. After stimulation with water, palmar hyperlinearity and whitish, translucent papules forming macerated-looking plaques with a central depression were observed. Dermoscopically, we observed whitish and anfractive structures with coral appearance and microdroplets of water. In the histological study, we observed continuous hyperkeratosis and acrosyringium dilation from the middle dermis to the stratum corneum. With the clinical presentation and histological findings, aquagenic keratoderma was diagnosed, and treatment was started with partial improvement. CONCLUSIONS: Aquagenic keratoderma is an underdiagnosed entity. Despite its indolent course, it could be considered as a marker of a systemic disease such as cystic fibrosis. Since the discussion about the terminology of the disease has arisen, we considered adjusting to a descriptive nomenclature, proposing the term whitish macerated aquagenic plaques of the acrosyringium. It is necessary to continue reporting these cases to understand the disease better and offer adequate management and comprehensive follow-up to the patients.
INTRODUCCIÓN: La queratodermia acuagénica se desencadena tras el contacto de las palmas de las manos y las plantas de los pies con el agua. Se caracteriza por la aparición de pápulas translúcidas que forman placas de aspecto macerado. Puede asociarse con el consumo de ciertos medicamentos y con afecciones como la fibrosis quística, la atopia y la desnutrición, o ser idiopática. CASO CLÍNICO: Se describe el caso de una paciente de 17 años con dolor abdominal crónico funcional. Presentó una dermatosis de 2 meses de evolución que afectaba las palmas con «arrugamiento¼ después del contacto con el agua. Tras el estímulo con el agua, se observaron hiperlinealidad palmar y pápulas blanquecinas y translúcidas que formaban placas de aspecto macerado con una depresión central. Dermatoscópicamente se observaron estructuras blanquecinas anfractuosas de apariencia coraliforme y microgotas de agua. En el estudio histológico se observaron hiperqueratosis continua y dilatación del acrosiringio desde la dermis media hasta el estrato córneo. Con el cuadro clínico y los hallazgos histológicos, se confirmó el diagnóstico de queratodermia acuagénica y se inició el tratamiento, con el que se observó una mejoría parcial. CONCLUSIONES: La queratodermia acuagénica es una afección subdiagnosticada y poco reportada. A pesar de cursar de forma indolente, puede considerarse como un marcador de enfermedad sistémica como la fibrosis quística. Ya que existe discusión sobre la nomenclatura de la enfermedad, consideramos ajustarnos a una nomenclatura descriptiva, como «placas blanquecinas y maceradas acuagénicas del acrosiringio¼. Es necesario continuar reportando estos casos para comprender mejor la enfermedad, ofrecer un manejo adecuado y dar seguimiento integral a los pacientes.
Assuntos
Fibrose Cística , Ceratodermia Palmar e Plantar , Feminino , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/tratamento farmacológico , Ceratodermia Palmar e Plantar/etiologia , ÁguaRESUMO
Resumen Introducción: La queratodermia acuagénica se desencadena tras el contacto de las palmas de las manos y las plantas de los pies con el agua. Se caracteriza por la aparición de pápulas translúcidas que forman placas de aspecto macerado. Puede asociarse con el consumo de ciertos medicamentos y con afecciones como la fibrosis quística, la atopia y la desnutrición, o ser idiopática. Caso clínico: Se describe el caso de una paciente de 17 años con dolor abdominal crónico funcional. Presentó una dermatosis de 2 meses de evolución que afectaba las palmas con «arrugamiento¼ después del contacto con el agua. Tras el estímulo con el agua, se observaron hiperlinealidad palmar y pápulas blanquecinas y translúcidas que formaban placas de aspecto macerado con una depresión central. Dermatoscópicamente se observaron estructuras blanquecinas anfractuosas de apariencia coraliforme y microgotas de agua. En el estudio histológico se observaron hiperqueratosis continua y dilatación del acrosiringio desde la dermis media hasta el estrato córneo. Con el cuadro clínico y los hallazgos histológicos, se confirmó el diagnóstico de queratodermia acuagénica y se inició el tratamiento, con el que se observó una mejoría parcial. Conclusiones: La queratodermia acuagénica es una afección subdiagnosticada y poco reportada. A pesar de cursar de forma indolente, puede considerarse como un marcador de enfermedad sistémica como la fibrosis quística. Ya que existe discusión sobre la nomenclatura de la enfermedad, consideramos ajustarnos a una nomenclatura descriptiva, como «placas blanquecinas y maceradas acuagénicas del acrosiringio¼. Es necesario continuar reportando estos casos para comprender mejor la enfermedad, ofrecer un manejo adecuado y dar seguimiento integral a los pacientes.
Abstract Background: Aquagenic keratoderma is triggered in the palms and soles after contact with water, and is characterized by the appearance of translucent papules forming macerated plaques. It may be associated with medications and diseases such as cystic fibrosis, atopy, and malnutrition, or be idiopathic. Case report: We describe the case of a 17-year-old female patient with chronic functional abdominal pain. She presented with a 2-month history of "wrinkling" of palms after contact with water. After stimulation with water, palmar hyperlinearity and whitish, translucent papules forming macerated-looking plaques with a central depression were observed. Dermoscopically, we observed whitish and anfractive structures with coral appearance and microdroplets of water. In the histological study, we observed continuous hyperkeratosis and acrosyringium dilation from the middle dermis to the stratum corneum. With the clinical presentation and histological findings, aquagenic keratoderma was diagnosed, and treatment was started with partial improvement. Conclusions: Aquagenic keratoderma is an underdiagnosed entity. Despite its indolent course, it could be considered as a marker of a systemic disease such as cystic fibrosis. Since the discussion about the terminology of the disease has arisen, we considered adjusting to a descriptive nomenclature, proposing the term whitish macerated aquagenic plaques of the acrosyringium. It is necessary to continue reporting these cases to understand the disease better and offer adequate management and comprehensive follow-up to the patients.
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Low doses of mercury (Hg) promote deleterious effects on cardiovascular system, but the mechanisms implicated remain unclear. This study analyzed whether angiotensin II AT-1 receptors are involved in the vascular dysfunction caused by chronic exposure to low HgCl2 doses. For this, rats were divided into four groups and untreated (saline by im injections and tap water by gavage) or treated for 30 days as follows: Mercury (HgCl2im, first dose of 4.6⯵gâ¯kg-1 and subsequent doses of 0.07⯵gâ¯kg-1 day-1, and tap water by gavage); Losartan (saline im and losartan, 15â¯mgâ¯kg-1 day-1, by gavage); Losartan-Mercury (HgCl2im and Losartan by gavage). Systolic blood pressure was measured by tail plethysmography, vascular reactivity in aorta by isolated organ bath, oxidative stress by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and antioxidant capacity (FRAP) and protein expression of AT-1 receptors by Western Blot. As results, co-treatment with losartan prevented the increased aortic vasoconstrictor responses to phenylephrine (Phe), the involvement of ROS and prostanoids on the response to Phe and the reduced negative endothelial modulation by nitric oxide on these responses. Moreover, this co-treatment avoided the increase in plasmatic and vascular oxidative stress and AT-1 protein expression in aorta. In conclusion, these results suggest that AT-1 receptors upregulation might play a key role in the vascular damage induced by Hg exposure by increasing oxidative stress and probably by reducing NO bioavailability.
Assuntos
Angiotensina II , Mercúrio , Estresse Oxidativo , Receptor Tipo 1 de Angiotensina , Receptores de Angiotensina , Angiotensina II/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Endotélio Vascular , Mercúrio/toxicidade , Ratos , Ratos Wistar , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores de Angiotensina/efeitos dos fármacos , Receptores de Angiotensina/metabolismo , Regulação para Cima , VasoconstriçãoRESUMO
Mercury is a ubiquitous environmental pollutant and mercury contamination and toxicity are serious hazards to human health. Some studies have shown that mercury impairs male reproductive function, but less is known about its effects following exposure at low doses and the possible mechanisms underlying its toxicity. Herein we show that exposure of rats to mercury chloride for 30 days (first dose 4.6µgkg-1, subsequent doses 0.07µgkg-1day-1) resulted in mean (±s.e.m.) blood mercury concentrations of 6.8±0.3ngmL-1, similar to that found in human blood after occupational exposure or released from removal of amalgam fillings. Even at these low concentrations, mercury was deposited in reproductive organs (testis, epididymis and prostate), impaired sperm membrane integrity, reduced the number of mature spermatozoa and, in the testes, promoted disorganisation, empty spaces and loss of germinal epithelium. Mercury increased levels of reactive oxygen species and the expression of glutathione peroxidase (GPx) 1 and GPx4. These results suggest that the toxic effects of mercury on the male reproductive system are due to its accumulation in reproductive organs and that the glutathione system is its potential target. The data also suggest, for the first time, a possible role of the selenoproteins GPx1 and GPx4 in the reproductive toxicity of mercury chloride.
Assuntos
Glutationa Peroxidase/metabolismo , Mercúrio/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Epididimo/efeitos dos fármacos , Epididimo/metabolismo , Glutationa/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismoRESUMO
Mercury is a toxic and bio-accumulative heavy metal of global concern. While good deals of research have been conducted on the toxic effects of mercury, little is known about the mechanisms involved in the pathogenesis of male reproductive dysfunction induced by mercury. Therefore, the purpose of this study was to assess the effects and underlying mechanisms of chronic mercury exposure at low levels on male reproductive system of rats. Three-month-old male Wistar rats were divided into two groups and treated for 60 days with saline (i.m., Control) and HgCl2 (i.m. 1st dose: 4.6 µg/kg, subsequent doses 0.07 µg/kg/day). We analyzed sperm parameters, hormonal levels and biomarkers of oxidative stress in testis, epididymis, prostate and vas deferens. Mercury treatment decreased daily sperm production, count and motility and increased head and tail morphologic abnormalities. Moreover, mercury treatment decreased luteinizing hormone levels, increased lipid peroxidation on testis and decreased antioxidant enzymes activities (superoxide dismutase and catalase) on reproductive organs. Our data demonstrate that 60-day chronic exposure to low concentrations of HgCl2 impairs sperm quality and promotes hormonal imbalance. The raised oxidative stress seems to be a potential mechanism involved on male reproductive toxicity by mercury.
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Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Imunoensaio , Peroxidação de Lipídeos/efeitos dos fármacos , Hormônio Luteinizante/análise , Masculino , Ratos , Ratos Wistar , Contagem de Espermatozoides , Superóxido Dismutase/metabolismo , Testosterona/análise , Fatores de TempoRESUMO
Hypertension is considered as a low-grade inflammatory disease, with adaptive immunity being an important mediator of this pathology. TLR4 may have a role in the development of several cardiovascular diseases; however, little is known about its participation in hypertension. We aimed to investigate whether TLR4 activation due to increased activity of the renin-angiotensin system (RAS) contributes to hypertension and its associated endothelial dysfunction. For this, we used aortic segments from Wistar rats treated with a non-specific IgG (1 µg/day) and SHRs treated with losartan (15 mg/kg·day), the non-specific IgG or the neutralizing antibody anti-TLR4 (1 µg/day), as well as cultured vascular smooth muscle cells (VSMC) from Wistar and SHRs. TLR4 mRNA levels were greater in the VSMC and aortas from SHRs compared with Wistar rats; losartan treatment reduced those levels in the SHRs. Treatment of the SHRs with the anti-TLR4 antibody: 1) reduced the increased blood pressure, heart rate and phenylephrine-induced contraction while it improved the impaired acetylcholine-induced relaxation; 2) increased the potentiation of phenylephrine contraction after endothelium removal; and 3) abolished the inhibitory effects of tiron, apocynin and catalase on the phenylephrine-induced response as well as its enhancing effect of acetylcholine-induced relaxation. In SHR VSMCs, angiotensin II increased TLR4 mRNA levels, and losartan reduced that increase. CLI-095, a TLR4 inhibitor, mitigated the increases in NAD(P)H oxidase activity, superoxide anion production, migration and proliferation that were induced by angiotensin II. In conclusion, TLR4 pathway activation due to increased RAS activity is involved in hypertension, and by inducing oxidative stress, this pathway contributes to the endothelial dysfunction associated with this pathology. These results suggest that TLR4 and innate immunity may play a role in hypertension and its associated end-organ damage.
Assuntos
Angiotensina II/farmacologia , Aorta/fisiopatologia , Hipertensão/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like/metabolismo , Regulação para Cima/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Antioxidantes/farmacologia , Aorta/efeitos dos fármacos , Aorta/patologia , Pressão Sanguínea/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/genética , Hipertensão/patologia , Técnicas In Vitro , Masculino , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenilefrina/farmacologia , Ratos Endogâmicos SHR , Ratos Wistar , Superóxidos/metabolismo , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genética , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
Mercury (Hg) is a widespread environmental pollutant that adversely affects the male reproductive system. The precise mechanisms underlying mercuric chloride (HgCl2)-induced toxicity are not fully understood; however, evidence indicates that oxidative stress may be involved in this process. Although the adverse effects of high levels of inorganic Hg on the male reproductive system have been investigated, the effects of low levels of exposure are unknown. Therefore, the aim of this study was to investigate the effects of chronic exposure to low concentrations of HgCl2 on sperm parameters, lipid peroxidation, and antioxidant activity of male rats. Three-month-old male Wistar rats were treated for 30 d and divided into groups: control (saline, i.m.) and HgCl2 group (i.m., first dose 4.6 µg/kg, subsequent doses 0.07 µg/kg/d). Sperm parameters (count, motility and morphology) and biomarkers of oxidative stress in testis, epididymis, prostate, and vas deferens were analyzed. Mercury treatment produced a reduction in sperm quantity (testis and epididymis) and daily sperm production, following by decrease in sperm motility and increase on head and tail morphologic abnormalities. HgCl2 exposure was correlated with enhanced oxidative stress in reproductive organs, represented not only by augmented lipid peroxidation but also by changes in antioxidant enzymes activity superoxide dismutase (SOD) and catalase (CAT) and nonprotein thiol levels. In conclusion, chronic exposure to low doses of Hg impaired sperm quality and adversely affected male reproductive functions, which may be due, at least in part, to enhanced oxidative stress.
Assuntos
Poluentes Ambientais/toxicidade , Cloreto de Mercúrio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Espermatozoides/fisiologia , Testes de Toxicidade CrônicaRESUMO
UNLABELLED: Mercury increases the risk of cardiovascular disease and oxidative stress and alters vascular reactivity. This metal elicits endothelial dysfunction causing decreased NO bioavailability via increased oxidative stress and contractile prostanoid production. NADPH oxidase is the major source of reactive oxygen species (ROS) in the vasculature. Our aim was to investigate whether treatment with apocynin, an NADPH oxidase inhibitor, prevents the vascular effects caused by chronic intoxication with low concentrations of mercury. Three-month-old male Wistar rats were treated for 30 days with a) intramuscular injections (i.m.) of saline; b) HgCl(2) (i.m. 1(st) dose: 4.6 µg/kg, subsequent doses: 0.07 µg/kg/day); c) Apocynin (1.5 mM in drinking water plus saline i.m.); and d) Apocynin plus HgCl(2). The mercury treatment resulted in 1) an increased aortic vasoconstrictor response to phenylephrine and reduced endothelium-dependent responses to acetylcholine; 2) the increased involvement of ROS and vasoconstrictor prostanoids in response to phenylephrine, whereas the endothelial NO modulation of such responses was reduced; and 3) the reduced activity of aortic superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increased plasma malondialdehyde (MDA) levels. Treatment with apocynin partially prevented the increased phenylephrine responses and reduced the endothelial dysfunction elicited by mercury treatment. In addition, apocynin treatment increased the NO modulation of vasoconstrictor responses and aortic SOD activity and reduced plasma MDA levels without affecting the increased participation of vasoconstrictor prostanoids observed in aortic segments from mercury-treated rats. CONCLUSIONS: Mercury increases the vasoconstrictor response to phenylephrine by reducing NO bioavailability and increasing the involvement of ROS and constrictor prostanoids. Apocynin protects the vessel from the deleterious effects caused by NADPH oxidase, but not from those caused by prostanoids, thus demonstrating a two-way action.