RESUMEN
OBJECTIVE: Glucocorticoids (GCs) remain a cornerstone of the initial management of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), but have several dose-dependent side effects, in particular infections. The optimal dosing and tapering of oral GCs for remission induction are unknown. A systematic review and meta-analysis was undertaken to determine the efficacy and safety of low- versus high-dose GC regimens. METHOD: A systematic search of MEDLINE, Embase, and PubMed databases was conducted. Clinical studies using a GC-based induction protocol were selected. A daily dose of 0.5 mg/kg or < 30 mg/day oral prednisolone equivalent by the start of week 4 of the induction tapering schedule marked the threshold between high- and low-dose GCs. Risk ratios (RRs) were calculated by the random effects model for outcomes of remission and infection. Relapse events were summarized using risk differences with 95% confidence intervals (CIs). RESULTS: In total, 1145 participants were included in three randomized controlled trials and two observational studies, of whom 543 were assigned to the low-dose GC group and 602 to the high-dose GC group. A low-dose GC regimen was non-inferior to high-dose GCs with respect to outcomes of remission (RR 0.98, 95% CI 0.95-1.02, p = 0.37; I2 = 0%) and relapse (risk difference 0.03, 95% CI -0.01 to 0.06, p = 0.15; I2 = 12%), while significantly reducing the incidence of infection (RR 0.60, 95% CI 0.39-0.91, p = 0.02; I2 = 65%). CONCLUSION: Studies with low-dose GC regimens in AAV are associated with fewer infections while obtaining equivalent efficacy.
Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Glucocorticoides , Humanos , Glucocorticoides/uso terapéutico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Inducción de Remisión , Recurrencia , Citoplasma , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Mast cells contain granules packed with a mixture of proteins that are released on degranulation. The proteoglycan serglycin carries an array of glycosaminoglycan (GAG) side chains, sometimes heparin, sometimes chondroitin or dermatan sulphate. Tight packing of granule proteins is dependent on the presence of serglycin carrying these GAGs. The GAGs of mast cells were most intensively studied in the 1970s and 1980s, and though something is known about the fine structure of chondroitin sulphate and dermatan sulphate in mast cells, little is understood about the composition of the heparin/heparan sulphate chains. Recent emphasis on the analysis of mast cell heparin from different species and tissues, arising from the use of this GAG in medicine, lead to the question of whether variations within heparin structures between mast cell populations are as significant as variations in the mix of chondroitins and heparins.
Asunto(s)
Sulfatos de Condroitina/química , Dermatán Sulfato/química , Heparina/química , Mastocitos/química , Proteoglicanos/química , Proteínas de Transporte Vesicular/química , Animales , Conformación de Carbohidratos , Secuencia de Carbohidratos , Degranulación de la Célula , Células Cultivadas , Gránulos Citoplasmáticos/química , Humanos , Mastocitos/citología , Péptido Hidrolasas/química , Péptido Hidrolasas/metabolismo , Unión Proteica , Proteoglicanos/metabolismo , Relación Estructura-Actividad , Proteínas de Transporte Vesicular/metabolismoRESUMEN
Hexamidine (HEX) has been used as a preservative in topical preparations since the 1950s. A number of studies also indicate that the molecule plays a beneficial role in skin homoeostasis. In this review, we describe the physicochemical properties of hexamidine diisethionate (HEX D) and the corresponding hydrochloride salt (HEX H). The biocidal and protease inhibition properties of HEX are outlined as well as the effects of HEX on lipid processing enzymes, corneocyte maturity, stratum corneum thickness and transepidermal water loss (TEWL). Skin permeation properties of HEX D and HEX H are summarized, and formulation approaches for effective dermal targeting of HEX are discussed.
Asunto(s)
Cosméticos , Administración Tópica , Benzamidinas/administración & dosificación , Benzamidinas/química , Benzamidinas/farmacología , Humanos , Sales (Química)/química , Piel/efectos de los fármacosRESUMEN
BACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor-alpha (TNF-alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL-beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also examined. KEY RESULTS: Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil-endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS AND IMPLICATIONS: These data suggest that an optimum chain length of heparin possibly exists for certain non-anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti-inflammatory actions.
Asunto(s)
Anticoagulantes/farmacología , Heparina/farmacología , Neutrófilos/efectos de los fármacos , Adhesión Celular , Fraccionamiento Químico , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Humanos , Técnicas In Vitro , Interleucina-1beta/fisiología , Peso Molecular , N-Formilmetionina Leucil-Fenilalanina , Neutrófilos/metabolismo , Elastasa Pancreática/efectos de los fármacos , Elastasa Pancreática/metabolismo , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/fisiología , Venas Umbilicales/citologíaRESUMEN
Giardia intestinalis is the commonest gastrointestinal protozoal pathogen worldwide, and causes acute and chronic diarrhoea with malabsorption. First-line treatment is with a nitroimidazole, with a reported efficacy rate of 89%. Failure of treatment can occur in patients with hypogammaglobulinaemia or human immunodeficiency virus (HIV), or be due to nitroimidazole-resistant organisms. There is little evidence to guide the clinical management of nitroimidazole-refractory disease. We performed a retrospective audit of nitroimidazole-refractory giardiasis in returned travellers at the Hospital for Tropical Diseases, London between 2011 and 2013. Seventy-three patients with microscopy-proven or PCR-proven giardiasis in whom nitroimidazole treatment had failed were identified, and their management was investigated. In 2008, nitroimidazole treatment failed in 15.1% of patients. This increased to 20.6% in 2011 and to 40.2% in 2013. Patient demographics remained stable during this period, as did routes of referral. Of patients with giardiasis, 39.0% had travelled to India; this rose to 69.9% in patients with nitroimidazole-refractory disease. Of the patients with refractory disease, 44.6% had HIV serological investigations performed and 36.5% had immunoglobulin levels determined. Patients with refractory disease were treated with various agents, including albendazole, nitazoxanide, and mepacrine, alone or in combination. All 20 patients who received a mepacrine-containing regimen were cured. This data shows a worrying increase in refractory disease, predominantly in travellers from India, which is likely to represent increasing nitroimidazole resistance. Improved tools for the diagnosis of resistant G. intestinalis are urgently needed to establish the true prevalence of nitroimidazole-resistant giardiasis, together with clinical trials to establish the most effective second-line agent for empirical treatment regimens.
Asunto(s)
Antiprotozoarios/farmacología , Resistencia a Medicamentos , Giardia lamblia/efectos de los fármacos , Giardia lamblia/aislamiento & purificación , Giardiasis/epidemiología , Giardiasis/parasitología , Nitroimidazoles/farmacología , Adulto , Albendazol/uso terapéutico , Antiprotozoarios/uso terapéutico , Femenino , Giardiasis/tratamiento farmacológico , Hospitales , Humanos , Incidencia , Londres/epidemiología , Masculino , Nitrocompuestos , Quinacrina/uso terapéutico , Estudios Retrospectivos , Tiazoles/uso terapéutico , Viaje , Insuficiencia del TratamientoRESUMEN
Fourteen adult patients with chronic atopic dermatitis and active skin lesions had a skin biopsy and venous blood sample taken on the same day. Absolute numbers of circulating lymphocytes were normal in all patients. Fluorescence-activated cell sorter (FACS) analysis revealed normal numbers of total T lymphocytes and T-helper and T-suppressor subsets (helper:suppressor ratio, 2:1) in the atopic patients' peripheral blood, but an increase in circulating B lymphocytes and in HLA-D-related antigen-bearing cells. The skin biopsy showed a dermal infiltrate of predominantly T-helper lymphocytes (helper:suppressor ratio, 7:1). These cells showed strong HLA-DR plasma membrane staining. There was no HLA-DR staining in the membranes of epidermal keratinocytes. Using a monoclonal antihuman IgE, positive staining was observed in the dermis, though none was identified in the epidermis. The dermal anti-IgE staining was concentrated around clusters of T lymphocytes.
Asunto(s)
Células Sanguíneas/inmunología , Dermatitis Atópica/inmunología , Monocitos/inmunología , Piel/inmunología , Adolescente , Adulto , Separación Celular , Dermatitis Atópica/sangre , Dermatitis Atópica/genética , Femenino , Citometría de Flujo , Antígenos HLA-DR/análisis , Humanos , Técnicas para Inmunoenzimas , Inmunoglobulina E/metabolismo , Masculino , Persona de Mediana Edad , Fenotipo , Piel/metabolismoRESUMEN
1. The effects of unfractionated heparin (UH) and a selectively O-desulphated derivative of heparin (ODSH), lacking anticoagulant activity, on the adhesion of human peripheral blood mononuclear cells (HPBMNC) to human stimulated umbilical vein endothelial cells (HUVECs), were investigated. 2. For comparison, the effects of poly-L-glutamic acid (PGA), a large polyanionic molecule without sulphate groups and two different molecular weight sulphated dextrans (DS 5 k and DS 10 k) were studied. 3. UH (50 - 1000 u ml(-1)) significantly (P<0.05) inhibited the adhesion of HPBMNC to HUVECs, stimulated with IL-1beta (100 u ml(-1)), TNF-alpha (1000 u ml(-1)) or LPS (100 microg ml(-1)), when the drugs were added together with stimuli to HUVECs and coincubated for 6 h. Such effects on adhesion occurred with limited influence on expression of relevant endothelial adhesion molecules (ICAM-1 and VCAM-1). 4. UH (100 - 1000 u ml(-1)), when added to prestimulated HUVECs, significantly (P<0.05) increased adhesion of mononuclear cells to endothelium at the higher concentrations tested, without any effect on adhesion molecule expression. In contrast, the opposite effect was observed when human polymorphonuclear leucocyte adhesion was examined, under the same experimental conditions, suggesting that the observed potentiation of HPBMNC adhesion is cell specific. 5. The effects of UH on HPBMNC adhesion were shared by the non-anticoagulant ODSH (600 - 6000 microg ml(-1)) but not by sulphated dextrans or PGA (300 - 6000 microg ml(-1)). 6. Heparin affects the adhesion of HPBMNC to stimulated endothelium, in both an inhibitory and potentiating manner, effects which are unrelated to its anticoagulant activity and not solely dependent on molecular charge characteristics.
Asunto(s)
Adhesión Celular/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Heparina/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Línea Celular , Sulfato de Dextran/química , Sulfato de Dextran/farmacología , Relación Dosis-Respuesta a Droga , Endotelio Vascular/citología , Humanos , Molécula 1 de Adhesión Intercelular/farmacología , Interleucina-1/farmacología , Leucocitos Mononucleares/citología , Lipopolisacáridos/farmacología , Peso Molecular , Ácido Poliglutámico/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Venas Umbilicales/citología , Venas Umbilicales/efectos de los fármacos , Molécula 1 de Adhesión Celular Vascular/farmacologíaRESUMEN
1. The effects of an unfractionated heparin preparation (Multiparin), a low molecular weight heparin preparation (Fragmin) and a selectively O-desulphated derivative of heparin lacking anticoagulant activity, have been investigated for their effects on the adhesion of human polymorphonuclear leucocytes (PMNs) to cultured human umbilical vein endothelial cells (HUVECs) in vitro. The effect of poly-L-glutamic acid, a large, polyanionic molecule was also studied. 2. Unfractionated heparin (50-1000 U ml-1), the O-desulphated derivative (0.3-6 mg ml-1) and the low molecular weight heparin (50 U-1000 U ml-1) all inhibited significantly the adhesion of 51Cr labelled PMNs to HUVECs stimulated with interleukin-1 beta (IL-1 beta; 10 U ml-1), bacterial lipopolysaccharide (LPS; 2.5 micrograms ml-1) or tumour necrosis factor-alpha (TNF-alpha; 125 U ml-1) for 6 h, whereas poly-L-glutamic acid had no effect. In addition, the three heparin preparations in the same concentration range inhibited significantly the adhesion of f-met-leu-phe-stimulated PMNs to resting HUVECs. 3. The effects of unfractionated heparin upon the expression of adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and E-selection were also investigated, as were the effects of unfractionated heparin upon adhesion of human PMNs to previously stimulated HUVECs. Heparin had little effect upon levels of expression of these adhesion molecules on stimulated HUVECs. However, a profound effect upon PMN adhesion to previously stimulated HUVECs was demonstrated using the same preparation, suggesting that inhibition of adhesion molecule expression is not a major component of the described inhibitory effects of heparin. 4. Pre-incubation of PMNs with heparin followed by washing inhibited their adhesion to HUVECs, under different conditions of cellular activation, implying that heparin can bind to these cells and exert its anti-adhesive effects even when not directly present in the system. 5. These observations would suggest that both heparin and a low molecular weight heparin are capable of inhibiting adhesion of human PMNs to endothelial cells, an effect not dependent solely upon the polyanionic nature of these molecules, nor dependent upon their ability to act as anticoagulants.
Asunto(s)
Anticoagulantes/farmacología , Endotelio Vascular/citología , Heparina/análogos & derivados , Heparina/farmacología , Neutrófilos/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Línea Celular , Endotelio Vascular/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Humanos , Indicadores y Reactivos , Interleucina-1/farmacología , Lipopolisacáridos/farmacología , N-Formilmetionina Leucil-Fenilalanina/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Cordón Umbilical/citología , Cordón Umbilical/efectos de los fármacosRESUMEN
Of 73 adult patients attending a clinic specially provided to treat patients with atopic dermatitis, 31 (42%) showed one or more positive patch reaction on contact testing. There was a striking female preponderance in the patch test positive group (26F:5M) in contrast to those with negative test results (9F:17M). The commonest allergens identified were fragrances in 13 patients, nickel (7), rubber (5), lanolin (4) and formaldehyde (3). In 21 patients, topical preparations, cosmetic or medically prescribed, could be implicated. Contact sensitivity seems to be relatively common in adult patients who have a continuing problem with their atopic dermatitis. Recognizing this sensitization may be important in their management.
Asunto(s)
Dermatitis Alérgica por Contacto/complicaciones , Dermatitis Atópica/complicaciones , Adolescente , Adulto , Anciano , Niño , Dermatitis Alérgica por Contacto/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas del Parche , Perfumes/efectos adversos , Prueba de Radioalergoadsorción , Factores SexualesRESUMEN
An Indian atopic child presented with benign chronic bullous disease of childhood (BCBDC). HLA grouping did not show the typical finding of HLA B8 which questions the value of HLA typing in this condition.
Asunto(s)
Enfermedades Cutáneas Vesiculoampollosas , Enfermedad Crónica , Antígenos HLA/análisis , Antígenos HLA-B , Humanos , India/etnología , Lactante , Recién Nacido , Masculino , Escocia , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/inmunología , Enfermedades Cutáneas Vesiculoampollosas/terapiaRESUMEN
I have volunteered for many years for a woman's organization raising money to build trade and technical schools around the world, but I had never been asked to use my education as a nurse for this purpose. When the opportunity came for me and my classmates to join a volunteer mission to Honduras we jumped at the chance. Since we were all nurses we knew how to deliver patient care. This mission gave us the opportunity to use our newly acquired nurse practitioner skills. It also gave us the opportunity to see first hand how much need there is in other countries, as well as our own, for professional volunteers to help in multicultural settings.
Asunto(s)
Educación de Postgrado en Enfermería/organización & administración , Enfermeras Practicantes/organización & administración , Misiones Religiosas/organización & administración , Enfermería Transcultural/organización & administración , Honduras , Humanos , Enfermeras Practicantes/educación , Enfermeras Practicantes/psicología , Enfermería Transcultural/educación , Voluntarios/psicologíaRESUMEN
Research on Parkinson's disease (PD) has mainly focused on the degeneration of the dopaminergic neurons of nigro-striatal pathway; however, post-mortem studies have demonstrated that other brain regions such as the locus coeruleus (LC) and raphe nuclei (RN) are significantly affected as well. Degeneration of these crucial neuronal cell bodies may be responsible for depressive behavior and cognitive decline present in the pre-motor stage of PD. We have thus set out to create a pre-motor rodent model of PD which mimics the early stages of the condition. N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a selective noradrenergic neurotoxin, and parachloroampetamine (pCA), a selective serotonergic neurotoxin, were utilized concomitantly with bilateral 6-hydroxydopamine (6-OHDA) injections into the striatum to produce a pre-motor rodent model of PD with partial deficits in the dopaminergic, noradrenergic, and serotonergic systems. Our model exhibited a depressive/anhedonic condition as assessed using sucrose preference testing and the forced swim test. Our model also demonstrated deficits in object memory. These behavioral impairments were accompanied by a decline in both tissue and extracellular levels of all three neurotransmitters in both the frontal cortex and striatum. Immunohistochemistry also revealed a decrease in TH+ cells in the LC and substantia nigra. Exendin-4 (EX-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, promoted recovery of both the biochemical and behavioral dysfunction exhibited by our model. EX-4 was able to preserve the functional integrity of the dopaminergic, noradrenergic, and serotonergic systems. In conclusion, we have generated a novel animal model of PD that recapitulates certain pre-motor symptomology. These symptoms and causative physiology are ameliorated upon treatment with EX-4 and thus it could be used as a possible therapy for the non-motor symptoms prominent in the early stages of PD.
Asunto(s)
Encéfalo/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Norepinefrina/metabolismo , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Péptidos/uso terapéutico , Serotonina/metabolismo , Ponzoñas/uso terapéutico , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Dopamina/metabolismo , Exenatida , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Oxidopamina/envenenamiento , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/metabolismo , Enfermedad de Parkinson Secundaria/patología , Péptidos/farmacología , Ratas , Ratas Wistar , Reconocimiento en Psicología/efectos de los fármacos , Ponzoñas/farmacologíaRESUMEN
BACKGROUND AND PURPOSE Parkinson's disease (PD) is characterized by progressive dopaminergic cell loss; however, the noradrenergic system exhibits degeneration as well. Noradrenergic deficit in PD may be responsible for certain non-motor symptoms of the pathology, including psychiatric disorders and cognitive decline. The aim of this study was to generate a pre-motor rodent model of PD with noradrenergic denervation, and to assess whether treatment with exendin-4 (EX-4), a glucagon-like peptide 1 receptor agonist, could reverse impairment exhibited by our model. EXPERIMENTAL APPROACH We generated a model of PD utilizing N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine and 6-hydroxydopamine to create partial lesions of both the noradrenergic and dopaminergic systems respectively. We then assessed the validity of our model using an array of behavioural paradigms and biochemical techniques. Finally, we administered EX-4 over a 1 week period to determine therapeutic efficacy. KEY RESULTS Our model exhibits anhedonia and decreased object recognition as indicated by a decrease in sucrose preference, increased immobility in the forced swim test and reduced novel object exploration. Tissue and extracellular dopamine and noradrenaline were reduced in the frontal cortex and striatum. TH+ cell counts decreased in the locus coeruleus and substantia nigra. Treatment with EX-4 reversed behavioural impairment and restored extracellular/tissue levels of both dopamine and noradrenaline and TH+ cell counts. CONCLUSION AND IMPLICATIONS We conclude that early treatment with EX-4 may reverse certain neuropsychiatric dysfunction and restore dopamine and noradrenaline content.
Asunto(s)
Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Péptidos/uso terapéutico , Ponzoñas/uso terapéutico , Animales , Conducta Animal/efectos de los fármacos , Bencilaminas , Cerebro/metabolismo , Modelos Animales de Enfermedad , Dopamina/metabolismo , Exenatida , Masculino , Fármacos Neuroprotectores/farmacología , Norepinefrina/metabolismo , Oxidopamina , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/fisiopatología , Péptidos/farmacología , Ratas , Ratas Wistar , Ponzoñas/farmacologíaRESUMEN
BACKGROUND: Tecastemizole, a major metabolite of astemizole, is a potent and selective H1 receptor antagonist. Evidence suggests that this and certain other H1 receptor antagonists may possess anti-inflammatory effects that are, in some cases, independent of H1 receptor antagonism. Objective The aim of this study was to investigate the anti-inflammatory effects of tectastemizole in models of allergic inflammation. METHODS: Effects of tecastemizole were assessed in a murine model of allergic lung inflammation, in passive cutaneous anaphylaxis (PCA) responses in guinea-pig skin and in in vitro assays measuring endothelial adhesion molecule expression and leucocyte-endothelial adhesion. RESULTS: Tecastemizole inhibited antigen-induced eosinophil recruitment to the lungs of allergic mice in a dose-dependent manner. Furthermore, combination of a sub-effective dose of tecastemizole, combined with a sub-effective dose of dexamethasone inhibited eosinophil accumulation in this model. Plasma extravasation in PCA reactions was inhibited by tecastemizole, although by a mechanism that would appear to be H1 receptor-dependent. Cytokine-induced endothelial intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, as well as mononuclear cell adhesion to human umbilical vein endothelial cells was inhibited by tecastemazole in a manner independent of H1 receptor antagonism. CONCLUSION: These data suggest that tecastemizole may have H1 receptor-independent effects in inhibiting late-phase inflammatory responses, while acute responses appear to be inhibited in a H1 receptor-dependent manner. Furthermore, our data suggest an important potential steroid-sparing role for such drugs in the treatment of allergic inflammatory conditions.
Asunto(s)
Anafilaxia/inmunología , Bencimidazoles/farmacología , Dermatitis Atópica/inmunología , Antagonistas de los Receptores Histamínicos H1/farmacocinética , Piperidinas/farmacología , Receptores Histamínicos H1/inmunología , Hipersensibilidad Respiratoria/inmunología , Anafilaxia/tratamiento farmacológico , Anafilaxia/patología , Animales , Antiinflamatorios/farmacología , Astemizol/farmacología , Astemizol/uso terapéutico , Bencimidazoles/uso terapéutico , Adhesión Celular/efectos de los fármacos , Adhesión Celular/inmunología , Moléculas de Adhesión Celular , Movimiento Celular/efectos de los fármacos , Movimiento Celular/inmunología , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Dexametasona/farmacología , Modelos Animales de Enfermedad , Endotelio Vascular/inmunología , Endotelio Vascular/patología , Eosinófilos/inmunología , Eosinófilos/patología , Cobayas , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/patología , Molécula 1 de Adhesión Intercelular/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Piperidinas/uso terapéutico , Hipersensibilidad Respiratoria/tratamiento farmacológico , Hipersensibilidad Respiratoria/patología , Venas Umbilicales/inmunología , Venas Umbilicales/patología , Molécula 1 de Adhesión Celular Vascular/inmunologíaRESUMEN
BACKGROUND: While narrowband ultraviolet B (UVB) phototherapy is a well-established treatment for a range of skin conditions in adults, there is little in the literature about its use in children and data regarding its long-term carcinogenic potential are lacking. AIM: We undertook a retrospective review of the use of narrowband UVB phototherapy in a paediatric population attending two Glasgow Hospitals. METHODS: Phototherapy case notes for all children aged 16 years and under at time of treatment were reviewed at two hospital sites between 1996 and 2002. RESULTS: In total, 77 children had been treated (median age 12 years, range 4-16). The conditions treated most frequently were psoriasis (45%) and atopic eczema (32%). Other dermatoses treated included alopecia areata, acne, hydroa vacciniforme and polymorphic light eruption. Treatment courses for atopic conditions were longer than those required for psoriatic conditions: median number of treatments 24 for atopic eczema (range 3-46), and 17.5 for psoriasis (range 9-35). By the end of treatment, 68% of the atopic patients and 63% of the patients with psoriasis had cleared. The adverse event profile was similar to that in adults, with erythema, herpes simplex reactivation and PLE all recorded. Anxiety was a problem for five patients. CONCLUSION: We conclude that narrowband UVB phototherapy is a useful and well-tolerated treatment for children with severe or intractable inflammatory skin disease, but concerns remain regarding long-term side-effects.
Asunto(s)
Dermatitis Atópica/radioterapia , Psoriasis/radioterapia , Terapia Ultravioleta , Adolescente , Ansiedad/etiología , Vesícula/etiología , Niño , Preescolar , Eritema/etiología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Escocia , Resultado del Tratamiento , Terapia Ultravioleta/efectos adversos , Virosis/etiologíaRESUMEN
Neutrophil-derived proteases such as neutrophil elastase (NE) and matrix metalloproteinase (MMP) are implicated in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). In this study, the effects of selective phosphodiesterase (PDE) inhibition on NE and MMP-9 release, as well as Myeloperoxidase (MPO) activity and integrin-mediated neutrophil adhesion to human umbilical vein endothelial cells (HUVECs), were investigated. Human neutrophils were treated with PDE inhibitors (10(-11)-10(-4)M) in the absence and presence of TNF-alpha (tumour necrosis factor) (100 U ml(-1)) for 30 min, prior to fMLP activation. After 45 min, the cells were removed and NE, MPO and MMP-9 release assessed. In the adhesion studies, the neutrophils were radio-labelled with 51Cr, stimulated and immediately transferred to cultured HUVEC monolayers for 30 min, prior to assessment of adhesion. TNF-alpha (100 U ml(-1)) acted synergistically with fMLP in stimulating azurophil degranulation with respect to both MPO activity (P<0.01) and NE release (P<0.01). In contrast, an additive effect was observed with TNF-alpha and fMLP with regard to MMP-9 release and neutrophil adhesion to HUVECs. The PDE4 inhibitors, roflumilast, roflumilast N-oxide, cilomilast and rolipram significantly suppressed MPO, NE and MMP-9 release in both the presence and absence of TNF-alpha (P<0.05; n=6-10) and also reduced neutrophil adhesion to HUVECs. In contrast, milrinone, a PDE3 inhibitor and the non-selective PDE inhibitor, theophylline did not inhibit azurophil degranulation under any of the experimental conditions. These data provide further evidence that selective PDE4 isoenzyme inhibitors can inhibit neutrophil degranulation, effects not shared by PDE3 inhibitors or theophylline.