RESUMEN
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterized by focal lymphocytic infiltration of the exocrine glands causing dry eyes and dry mouth. Similar glandular features can also occur as a late complication in patients with other rheumatic disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and scleroderma ('secondary' Sjögren's syndrome).1 Anti-Ro and/or anti-La (ENA) antibodies are found in approximately 70% of pSS patients, generally with ANA positivity. Hypergammaglobulinaemia is also common. Systemic features also occur in some patients with pSS. A positive rheumatoid factor (RF) is often seen and so if patients present with arthritis, dryness and a positive RF a diagnosis of pSS should be considered as a possible alternative to RA. Anti-CCP antibodies are more specific for RA.
Asunto(s)
Síndrome de Sjögren/diagnóstico , Anticuerpos Antinucleares/sangre , Artritis Reumatoide/diagnóstico , Humanos , Hidroxicloroquina/uso terapéutico , Hipergammaglobulinemia/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Síndrome de Sjögren/tratamiento farmacológicoRESUMEN
Primary Sjögren's Syndrome (PSS) is characterized by dryness of the eyes and mouth due to lymphocytic infiltration of secretory exocrine glands. As well as disabling dryness, patients commonly have fatigue and arthralgia and an associated reduction in quality of life. The condition principally affects adult women and is relatively common--approximately 1:1000 to 1:250 adult women are estimated to have the condition in European/North American studies. Current therapy is principally symptomatic with the use of artificial tears and oral gels, pastilles and sprays. Medications to stimulate residual glandular secretion can be helpful for appropriate individuals. A proportion of patients also develop extraglandular features such as skin vasculitis, or lung, neurological, haematological or other systemic involvement. Conventional general immunosuppressive therapies such as corticosteroids or disease-modifying drugs, have been used in some patients with these clinical features. Biologic therapies specifically directed against molecules involved in disease pathogenesis represent a potentially more effective approach to therapeutic intervention in rheumatic diseases including PSS. The greatest experience in PSS is with rituximab, an anti-B-cell monoclonal antibody already in use for the treatment of B-cell lymphoma and rheumatoid arthritis. A randomised placebo controlled study is currently recruiting in France and a further study is planned in the UK. This review discusses the utility of biologic therapies in PSS, potential challenges for their use, the available data on rituximab and the potential role for other biologic therapies currently in development, or in clinical trials, in other autoimmune conditions.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Productos Biológicos/uso terapéutico , Síndrome de Sjögren/tratamiento farmacológico , Animales , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/clasificación , Productos Biológicos/administración & dosificación , Productos Biológicos/clasificación , Quimiocinas/inmunología , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/inmunología , Linfoma de Células B de la Zona Marginal/patología , Terapia Molecular Dirigida , Ensayos Clínicos Controlados Aleatorios como Asunto , Rituximab , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/patología , Resultado del TratamientoRESUMEN
OBJECTIVES: Fatigue is a prominent symptom in many rheumatic diseases and has a substantial impact on many outcomes. In previous research, fatigue has been linked with poor sleep and discomfort, including joint pain and sicca symptoms. The aim of the present study was to investigate prospectively the daily variations in fatigue and the roles of discomfort and adequacy of sleep the previous night in that fatigue for people with primary Sjögren's syndrome (pSS) or rheumatoid arthritis (RA). METHODS: Thirty-nine women with pSS or RA reported their discomfort and fatigue for 35 days using the Profile of Fatigue and Discomfort. Sleep was monitored with wrist actigraphy, and the quantity and quality of the night's sleep was reported in a diary each morning. RESULTS: The pattern of fatigue did not differ significantly between women with pSS and women with RA. For participants with either condition, both somatic and mental fatigue increased steadily throughout the day. Multi-level regressions indicated that evenings of worse discomfort were followed by poorer reported quantity/quality of sleep and worse sleep efficiency (percentage of time asleep when in bed). In addition, a night of worse discomfort and poor sleep was followed by more severe fatigue compared with the individual's average. CONCLUSIONS: Fatigue management for people with rheumatic disease could include strategies for coping with discomfort at night and difficulties in sleeping. Further research into ameliorating fatigue should include assessments of persistent discomfort or periods of insomnia and identify disease-specific needs that require targeted intervention.
Asunto(s)
Artritis Reumatoide/complicaciones , Ritmo Circadiano , Fatiga/etiología , Síndrome de Sjögren/complicaciones , Privación de Sueño/etiología , Adulto , Anciano , Artritis Reumatoide/fisiopatología , Fatiga/fisiopatología , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/fisiopatología , Privación de Sueño/fisiopatologíaRESUMEN
OBJECTIVES: The long-form 64-item Profile of Fatigue and Discomfort--Sicca Symptoms Inventory (PROFAD-SSI) questionnaire was developed as a patient-reported assessment tool for use in primary SS (PSS) and other rheumatic disorders. In this study, we assess whether the (shorter and more practical) 19-item PROFAD-SSI-SF (short form) gives similar results and whether a still briefer version using visual analogue scales (VASs) is feasible. METHODS: Questionnaire surveys comprising the long and short versions of the PROFAD-SSI were mailed to 43 patients with PSS and 50 patients with RA, who were asked to complete these contemporaneously as well as repeating the process 1 month later. PSS patients also completed a series of VASs comprising fatigue and sicca domains of the SSI. RESULTS: Surveys were returned from 35 PSS patients and 35 RA patients. All domains of the long- and short-form PROFAD-SSI showed strong correlations (Spearman rho between 0.779 and 0.996, P < 0.01). Factor analysis generally confirmed the previously validated domain structure with Cronbach's alpha = 0.99. The PROFAD-SF somatic fatigue domain correlated more strongly with a fatigue VAS than did the mental fatigue domain. The SSI-SF domain scores correlated with equivalent VAS scores. CONCLUSION: The long- and short-form PROFAD-SSI questionnaires correlate closely suggesting that the PROFAD-SF is valid as an outcome tool. Preliminary data also suggest that an even briefer form with compression of the domains into single VAS is also feasible.
Asunto(s)
Evaluación de la Discapacidad , Síndrome de Sjögren/psicología , Anciano , Fatiga , Femenino , Humanos , Persona de Mediana Edad , Psicometría , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/fisiopatología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To validate a tool for assessment of accumulated damage in patients with Primary SS (PSS). METHODS: Of the total 114 patients fulfilling American-European Consensus Group (AECG) criteria for PSS 104 were included in the study and assessed by rheumatologists at T (time) = 0 months and T = 12 months. On each occasion, damage and activity data, and autoantibody status were collected. SF-36 and Profile of Fatigue and Discomfort-Sicca Symptoms Inventory (PROFAD-SSI) questionnaires were completed. Cross-sectional analysis of this data was subject to a process of expert validation by 11 ophthalmologists, 14 oral medicine specialists and 8 rheumatologists. Items were removed from the index if >or= 50% of respondents recommended exclusion. Statistical validation was performed on remaining items. Spearman's rank analysis was used to investigate associations between damage scores and other disease status measures and Wilcoxon matched-pair analysis to assess sensitivity to change in the damage score. RESULTS: Based on the expert validation, a 29-item damage score was agreed incorporating ocular, oral and systemic domains. Total damage score correlated with disease duration at study entry (r = 0.436; P < 0.001), physical function as measured by SF-36 (r = 0.250, T = 0 months; r = 0.261 T = 12 months) and activity as measured by the Sjögren's Systemic Clinical Activity Index (r = 0.213, T = 0 months; r = 0.215, T =12 months). Ocular damage score correlated with the 'eye dry' domain of PROFAD-SSI (r = 0.228, T = 0 months; r = 0.365, T = 12 months). Other associations not present on both assessments were considered clinically insignificant. On Wilcoxon analysis, the index was sensitive to change over 12 months (z = -3.262; P < 0.01). CONCLUSION: This study begins validation of a tool for collection of longitudinal damage data in PSS. We recommend further trial in both the experimental and clinical environment.
Asunto(s)
Índice de Severidad de la Enfermedad , Síndrome de Sjögren/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Síndromes de Ojo Seco/diagnóstico , Métodos Epidemiológicos , Femenino , Humanos , Persona de Mediana Edad , Enfermedades de la Boca/diagnóstico , Factores de TiempoRESUMEN
OBJECTIVE: Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. METHODS: A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. RESULTS: There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. CONCLUSIONS: This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Fatiga/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales de Origen Murino , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada , Fatiga/etiología , Glucocorticoides/uso terapéutico , Humanos , Inmunosupresores/efectos adversos , Persona de Mediana Edad , Proyectos Piloto , Calidad de Vida , Rituximab , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: Fatigue is common in both Sjögren's syndrome (SS) and rheumatoid arthritis (RA) and can restrict functioning. AIMS: We tested the convergent validity of the Profile of Fatigue (ProF) using the Multidimensional Fatigue Inventory (MFI) in SS and RA. METHODS: The 16-item ProF and the 20-item MFI were completed by 82 White-British women aged 35-79 years (mean 60.4 years). Thirty-four had been diagnosed with SS for a mean of 7.0 years and 48 had been diagnosed with RA for a mean of 14.5 years. The ProF measures four somatic facets of fatigue and two mental facets; the MFI contains one mental and four somatic facets. The structures of the items from both measures were tested by principal component factor analysis using varimax rotation. RESULTS: No significant differences in fatigue were found between the women with SS or RA. Five factors explained a total of 76% of the variance of the MFI; six factors explained 94% of the variance of the ProF. Mental fatigue items from both questionnaires loaded onto separate factors from somatic fatigue items; the two original facets of mental fatigue in the ProF were replicated. The four somatic fatigue facets of the ProF were generally replicated but the somatic facets of the MFI did not replicate as clearly. Equivalent facets correlated well between the two questionnaires (r >or= 0.65). CONCLUSIONS: Both the ProF and the MFI distinguish between somatic and mental fatigue in SS and RA but the ProF appears better at resolving somatic facets of fatigue.
Asunto(s)
Artritis Reumatoide/complicaciones , Fatiga/etiología , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/complicaciones , Adulto , Anciano , Análisis de Varianza , Análisis Factorial , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
OBJECTIVE: This article describes the development of the Sjögren's Systemic Clinical Activity Index (SCAI) for the measurement of systemic disease activity in patients with primary Sjögren's syndrome (PSS). METHODS: A pilot tool was developed based on expert consensus and previous published data. One hundred and four patients with PSS were evaluated in a cross-sectional analysis, of whom 65 were reviewed at 3-monthly intervals, using this index, over a 12-month period. Factor analysis was used to evaluate the proposed domain structure. External validation was assessed by comparison with relevant domains of the Profile of Fatigue and Discomfort (PROFAD), Medical Outcomes Study Short Form-36 (SF-36) and The World Health Organization Quality of Life-Bref (WHOQOL-BREF). Sensitivity to change was assessed by comparing SCAI-derived flares with physician-designated disease flare and intention-to-treat analysis. A reliability and repeatability workshop was also held. RESULTS: Factor analysis supported the proposed domain structure. There were strong correlations between the SCAI fatigue, musculoskeletal and Raynaud's components and the PROFAD fatigue, arthralgia and vascular domains. There was a significant correlation between change in therapy and SCAI-defined flares (P = 0.01). The mean kappa-test results both for reliability of the SCAI and for physician repeatability were 0.71. CONCLUSION: This initial evaluation supports the potential for the SCAI as a tool for systemic activity assessment in patients with PSS but additional work is required to assess sensitivity to change in clinical therapeutic trials.
Asunto(s)
Fatiga/diagnóstico , Perfil de Impacto de Enfermedad , Síndrome de Sjögren/diagnóstico , Anciano , Ensayos Clínicos como Asunto , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Probabilidad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/clasificación , Factores de TiempoRESUMEN
OBJECTIVES: To analyse the healthcare usage, direct healthcare costs and predictors of cost in primary Sjögren's syndrome (PSS) in the UK and to compare the findings with the data from healthy control groups and rheumatoid arthritis (RA) patients. METHODS: A total of 129 patients with PSS (American-European criteria), 91 with RA and 92 controls, were included in the study. All groups were age-matched females and all completed questionnaires on health status (SF-36) and healthcare utilization (economic component of the Stanford Health Assessment Questionnaire). Annual direct healthcare costs were calculated (and expressed in 2004 UK pound sterling) and predictors of costs for each patient group were determined by regression analyses. Age, health status, disease duration and anti-Ro/La antibody positivity were used as potential predictor variables. RESULTS: Mean age was similar in the PSS (59.2 yrs, S.D. 11.6), RA (60.3 yrs, S.D. 10.5) and control groups (57.7 yrs, S.D. 12.5). The mean disease duration was 5.4 yrs (S.D. 4.8) in the PSS group and 13.4 yrs (S.D. 11.4) in the RA group. The mean annual total direct cost per patient [95% confidence interval (CI)] was 2188 pounds sterling (1831 and 2546 pounds sterling) in the PSS group, 2693 pounds sterling(2069 and 3428 pounds sterling) in the RA group and 949 pounds sterling (741 and 1156 pounds sterling) in the control group. The costs in the PSS group were greater than for the RA and control groups for visits to all healthcare professionals (total) as well as visits to the dentist, dental hospital and ophthalmologist. The costs in the PSS and RA groups were higher than in controls for diagnostic tests and visits to hospital and the accident and emergency (A&E) department. The PSS group also incurred higher costs than controls, but lower costs than the RA group, for visits to a rheumatologist, urine and blood tests, assistive devices and drug therapy. Regression analysis identified the SF-36 physical function subscale as the best predictor of costs in PSS patients as well as controls and the mental health subscale in RA patients. CONCLUSION: This is the first study to evaluate direct healthcare costs in patients with PSS. PSS has a significant impact on the healthcare system, similar to that of RA, by more than doubling costs compared with control patients.
Asunto(s)
Costos de la Atención en Salud/estadística & datos numéricos , Síndrome de Sjögren/economía , Medicina Estatal/economía , Adulto , Anciano , Artritis Reumatoide/economía , Artritis Reumatoide/terapia , Terapias Complementarias/economía , Costos Directos de Servicios/estadística & datos numéricos , Costos de los Medicamentos/estadística & datos numéricos , Empleo/estadística & datos numéricos , Femenino , Investigación sobre Servicios de Salud , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Perfil de Impacto de Enfermedad , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/terapia , Medicina Estatal/estadística & datos numéricos , Reino UnidoRESUMEN
The 6th European Lupus Meeting was held at the Royal College of Physicians of London and was attended by 450 delegates. The conference brought together leading speakers from Europe and North America who reviewed current knowledge and exciting new developments in both clinical and basic science aspects of systemic lupus erythematosus. This review summarizes the major points covered in each session.
Asunto(s)
Lupus Eritematoso Sistémico , Animales , Apoptosis , Arteriosclerosis , Autoanticuerpos , Autoantígenos , Biomarcadores , Proteínas del Sistema Complemento , Citocinas , Europa (Continente) , Humanos , Interferones , Nefritis Lúpica/etiología , Nefritis Lúpica/genética , Nefritis Lúpica/inmunología , Polimorfismo Genético , Proyectos de Investigación , Transducción de SeñalRESUMEN
OBJECTIVE: To analyse T cell receptor beta variable (TCRBV) gene polymorphisms (insertion/deletion related polymorphism (IDRP) and BV6S7) in primary Sjögren's syndrome (PSS). METHODS: Genomic DNA was extracted from blood samples from patients fulfilling the modified European criteria for PSS (n = 61). Healthy control blood samples were obtained from the Blood Transfusion Service (n = 121). As a disease control group, samples from patients with systemic lupus erythematosus (n = 42) were analysed. BV6S7 was genotyped using an established PCR/RFLP method. The IDRP was determined by comparison of the intensity of PCR product bands from within BV9S2 and an internal control region (BV9S1), to ascertain whether 0, 1, or 2 copies of the insertion were present. RESULTS: There was a decrease (p = 0.018) in the proportion of PSS patients with the deleted/deleted genotype. There was no association with specific BV6S7 alleles or genotypes with either the PSS group or the hypergammaglobulinaemic subgroup. There were no significant differences in haplotype frequencies after Bonferroni correction. CONCLUSIONS: A reduced proportion of patients with PSS have the deleted/deleted genotype. Eighty nine per cent of PSS patients have at least one extra germline copy of BV13S2*1. This may relate to previous observations of increased BV13 specific T cells and mRNA in the salivary glands.
Asunto(s)
Eliminación de Gen , Genes Codificadores de la Cadena beta de los Receptores de Linfocito T/genética , Polimorfismo Genético , Síndrome de Sjögren/genética , Frecuencia de los Genes , Haplotipos , Humanos , Lupus Eritematoso Sistémico/genética , Mutagénesis Insercional , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
OBJECTIVES: To test the hypothesis that fluoride varnish is effective in reducing demineralization (white spot) lesions adjacent to bonded orthodontic brackets. DESIGN: Two similar samples of extracted bovine incisors, with bonded orthodontic brackets, were separated into an experimental group (fluoride varnish was applied) and control group (no fluoride varnish) to examine the preventive effects of fluoride varnish. SETTING AND SAMPLE POPULATION: The dental clinic of the State University of Maringá--UEM (Maringá, Paraná, Brazil). Thirty-eight extracted bovine incisors with bonded orthodontic brackets. EXPERIMENTAL VARIABLE: Fluoride varnish was applied topically to half of the sample of extracted bovine teeth. No varnish was applied to the other half. OUTCOME MEASURE: The depths of enamel demineralization (white spot) lesions were measured from polarized light microscopy images using image analysis software. RESULTS: The teeth in both the experimental and control groups had been exposed to a cariogenic environment twice a day for 35 days. Those teeth that had been treated with two applications of fluoride varnish (one at the outset and another 15 days later) demonstrated about 38% less mean lesion depth than teeth where no varnish had been applied. CONCLUSION: Orthodontists may wish to consider the application of fluoride varnish during fixed orthodontic therapy to help reduce the development of enamel white spot lesions.
Asunto(s)
Cariostáticos/uso terapéutico , Esmalte Dental/efectos de los fármacos , Fluoruros Tópicos/uso terapéutico , Soportes Ortodóncicos , Desmineralización Dental/prevención & control , Animales , Bovinos , Recubrimiento Dental Adhesivo , Caries Dental/prevención & control , Procesamiento de Imagen Asistido por Computador , Laca , Microscopía de Polarización , Saliva Artificial/química , Cepillado DentalRESUMEN
OBJECTIVE: To establish the prevalence among women of primary Sjögren's syndrome (PSS) in Birmingham, UK. METHODS: Eight hundred and forty-six female Caucasians from two general practitioner lists were invited to complete a questionnaire that included a screening question on dry eyes and mouth. Individuals who responded positively were evaluated further. RESULTS: Overall, 65/% of individuals who were sent a questionnaire responded. Two had possible PSS, but were negative for anti-Ro/La antibodies. Our estimates of the prevalence of PSS ranged from < 0.1% up to 0.4%, depending on the assumptions used. CONCLUSION: Our data support previous studies suggesting a prevalence of PSS in the community of 0.1-0.6% rather than those suggesting a higher figure.
Asunto(s)
Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/epidemiología , Adulto , Distribución por Edad , Anciano , Medicina Familiar y Comunitaria , Femenino , Encuestas Epidemiológicas , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Probabilidad , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Reino Unido/epidemiología , Población UrbanaRESUMEN
OBJECTIVE: Fatigue is a prominent symptom in primary Sjögren's syndrome (PSS). We set out to compare existing instruments and a new tool for measuring fatigue and general discomfort in PSS, with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and healthy controls. METHODS: Groups of female Caucasian PSS patients completed a new questionnaire developed from PSS patients' own vocabulary, as well as the SF-36, WHOQOL-BREF and HAD scales. For comparison, the questionnaire was also completed by groups of SLE and RA patients and healthy controls. RESULTS: Each disease group differed significantly from healthy controls on each facet of fatigue and general discomfort in the new tool. Somatic fatigue was worst in RA, while mental fatigue was worst in PSS and SLE. The facets of somatic fatigue and discomfort in the new tool correlated well with comparable domains in existing scales. CONCLUSIONS: Fatigue in PSS can be measured using this new Sjögren's-based psychometric instrument. The new questionnaire tool was more sensitive than the SF-36, WHOQOL-BREF and HAD at distinguishing the three rheumatic disorders from controls.
Asunto(s)
Fatiga/diagnóstico , Índice de Severidad de la Enfermedad , Síndrome de Sjögren/diagnóstico , Adulto , Anciano , Artritis Reumatoide/complicaciones , Fatiga/etiología , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Fatiga Mental/diagnóstico , Fatiga Mental/etiología , Persona de Mediana Edad , Psicometría , Calidad de Vida , Sensibilidad y Especificidad , Síndrome de Sjögren/psicología , Encuestas y CuestionariosRESUMEN
KHEYLRF-NH(2) (AF2) is a FMRFamide-related peptide (FaRP) present in parasitic and free-living nematodes. At concentrations as low as 10 pM, AF2 induces a biphasic tension response, consisting of a transient relaxation followed by profound excitation, in neuromuscular strips prepared from Ascaris suum. In the present study, the effects of AF2 on cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and inositol-1,4,5-triphosphate (IP(3)) levels were measured following muscle tension recordings from 2 cm neuromuscular strips prepared from adult A. suum. AF2 induced a concentration- and time-dependent increase in cAMP, beginning at 1 nM; cAMP levels increased by 84-fold following 1 h exposure to 1 microM AF2. cGMP and IP(3) levels were unaffected by AF2 at concentrations =1 microM. AF2-induced stimulation of cAMP was unaffected by removal of the dorsal or ventral nerve cord, even though this form of denervation abolished the excitatory phase of the tension response. The effects of 0.1 and 1 microM AF2 on cAMP were also unaffected by 10 microM SDPNFLRF-NH(2) (PF1, an inhibitory FaRP) and 10 microM PF1022A (an inhibitory cyclodepsipeptide), even though each of these peptides abolished the excitatory phase of the tension response induced by AF2. Within an alanine-scan series of AF2 analogues, only KHAYLRF-NH(2) stimulated cAMP production with equipotency to AF2; the effects of this peptide on muscle tension also mimicked AF2. Another excitatory FaRP present in nematodes, KNEFIRF-NH(2) (AF1), also stimulated cAMP production, but was 100-fold less potent than AF2. The stimulatory effects of AF1 on tension and cAMP levels were blocked by an alanine-substituted analogue of this peptide (Ala(6)-AF1, KNEFIAF-NH(2)), while the stimulatory effects of AF2 on tension and cAMP were not affected by this analogue. AF2 and AF1 increase A. suum somatic muscle cAMP by targeting different receptors. Increases in cAMP stimulated by AF2 can be decoupled from the excitatory response caused by this peptide, and it is not possible to establish a causal linkage between the contractile response elicited by this peptide and its effects on cAMP accumulation.