RESUMEN
BACKGROUND: sensitivity to food antigens has been postulated as a contributing factor to the pathogenesis of IgA nephropathy (IgAN). METHODS: in this study we used a recently developed mucosal patch technique to evaluate rectal mucosal sensitivity to soy and cow's milk (CM) proteins in IgAN patients (n = 28) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analyzed for IgA and IgG antibodies to alpha-lactalbumin, beta-lactoglobulin, casein and soy. RESULTS: 14 of 28 (14/28) patients experienced a rectal mucosal reaction, measured by increased NO and/or MPO levels, upon rectal challenge with soy and/or cow's milk proteins. The levels of IgG antibodies to alpha-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, whereas the mean serum levels of IgA antibodies were similar. No differences were seen in serum levels of IgA or IgG antibodies to soy. CONCLUSION: it is concluded that approximately half of our IgAN patients have a rectal mucosal sensitivity to soy or CM, and that an immune reactivity against antigens may be involved in the pathogenesis of IgAN in this subgroup of patients.
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Hipersensibilidad a los Alimentos/epidemiología , Glomerulonefritis por IGA/epidemiología , Mucosa Intestinal/inmunología , Hipersensibilidad a la Leche/epidemiología , Proteínas de la Leche/efectos adversos , Proteínas de Soja/efectos adversos , Inmunidad Adaptativa , Adulto , Anciano , Estudios de Casos y Controles , Caseínas/efectos adversos , Proteína Catiónica del Eosinófilo/metabolismo , Femenino , Hipersensibilidad a los Alimentos/inmunología , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/fisiopatología , Humanos , Inmunidad Innata , Inmunidad Mucosa , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Pruebas Inmunológicas , Riñón/fisiopatología , Lactalbúmina/efectos adversos , Lactoglobulinas/efectos adversos , Masculino , Persona de Mediana Edad , Hipersensibilidad a la Leche/inmunología , Proteínas de la Leche/inmunología , Óxido Nítrico/metabolismo , Peroxidasa/metabolismo , Proteinuria/epidemiología , Recto , Proteínas de Soja/inmunología , Suecia/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVES: A dietary link to rheumatoid arthritis (RA) has been suspected and an influence on arthritic symptoms by different diets has been reported. Our primary aim was to record the self-experienced adverse food reactions in patients with RA. A secondary aim was to relate self-experienced adverse reactions to dairy produce and wheat to the local mucosal reactivity observed after rectal challenge with cow's milk protein (CM) and wheat gluten. METHODS: A questionnaire about self-experienced adverse reaction to food was sent to 347 RA patients. Rectal challenge with CM and gluten was performed in 27 of these patients and in healthy controls (n = 18). After a 15-h challenge the mucosal production of nitric oxide (NO) and the mucosal release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured by using the mucosal patch technique. RESULTS: Twenty-seven per cent of the RA patients reported food intolerance (FI) to various foods, and in particular to CM, meat, and wheat gluten. Strong mucosal reactivity to CM was observed in 11% of the patients. Moderately increased mucosal reactivity to CM and gluten was found in 22% and 33%, respectively, of the patients. No relationship was found between self-experienced adverse reactions to CM or gluten and mucosal reactivity to these proteins. CONCLUSIONS: Perceived FI is reported frequently by RA patients, with a prevalence similar to that reported previously in the general population. Mucosal reactivity to CM and gluten is seen in a minor fraction of RA patients and is not related to the frequently perceived intolerance to these proteins.
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Artritis Reumatoide/inmunología , Glútenes/efectos adversos , Hipersensibilidad a la Leche/inmunología , Proteínas de la Leche/efectos adversos , Recto/inmunología , Hipersensibilidad al Trigo/inmunología , Administración Rectal , Adulto , Artritis Reumatoide/complicaciones , Artritis Reumatoide/metabolismo , Femenino , Glútenes/administración & dosificación , Glútenes/inmunología , Glútenes/metabolismo , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina A/metabolismo , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Masculino , Persona de Mediana Edad , Hipersensibilidad a la Leche/complicaciones , Hipersensibilidad a la Leche/metabolismo , Proteínas de la Leche/administración & dosificación , Proteínas de la Leche/inmunología , Proteínas de la Leche/metabolismo , Membrana Mucosa/inmunología , Membrana Mucosa/metabolismo , Óxido Nítrico/metabolismo , Pruebas del Parche , Peroxidasa/metabolismo , Recto/metabolismo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Hipersensibilidad al Trigo/complicaciones , Hipersensibilidad al Trigo/metabolismoRESUMEN
INTRODUCTION: Patients with primary Sjögren's syndrome (pSS) are reported to have a variety of gastrointestinal symptoms partly attributed to an overrepresentation of celiac disease. We have observed that irritable bowel syndrome (IBS)-like symptoms are frequent complaints in this patient group. Allergic manifestations to various drugs are also common in pSS. A role of food allergy in IBS has been proposed. OBJECTIVE: This study is aimed at evaluating the mucosal response to rectal challenge with cow's milk protein (CM) in patients with pSS and relates possible CM reactivity to their intestinal symptoms. METHODS: A rectal challenge with CM was performed in 21 patients with pSS and 18 healthy controls. Fifteen hours after challenge the mucosal production of nitric oxide (NO) and the release of myeloperoxidase (MPO) as signs of mucosal inflammatory reaction were measured using the mucosal patch technique. RESULTS: Eight out of 21 patients with pSS had a definite increase of mucosal NO synthesis and the luminal release of MPO after rectal CM challenge. This sign of milk sensitivity was not linked to IgG/IgA antibodies to milk proteins. The symptoms for IBS according to Rome III criteria were fulfilled in 13 patients. All patients who were CM sensitive suffered from IBS. In a small open study, patients reactive to CM reported an improvement of intestinal symptoms on a CM-free diet. CONCLUSION: A rectal mucosal inflammatory response after CM challenge is seen in 38% of patients with pSS as a sign of CM sensitivity. IBS-like symptoms were common in pSS, linked to CM sensitivity.
Asunto(s)
Síndrome del Colon Irritable/complicaciones , Hipersensibilidad a la Leche/complicaciones , Proteínas de la Leche/efectos adversos , Síndrome de Sjögren/complicaciones , Adulto , Anciano , Animales , Bovinos , Femenino , Antígenos HLA-DQ/análisis , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Síndrome del Colon Irritable/inmunología , Masculino , Persona de Mediana Edad , Hipersensibilidad a la Leche/diagnóstico , Hipersensibilidad a la Leche/inmunología , Membrana Mucosa/inmunología , Membrana Mucosa/metabolismo , Óxido Nítrico/metabolismo , Pruebas del Parche/métodos , Peroxidasa/metabolismo , Recto/inmunología , Recto/metabolismo , Síndrome de Sjögren/inmunología , Estadísticas no ParamétricasRESUMEN
Patients with coeliac disease (CD) on a gluten-free diet may still have gastrointestinal symptoms. On clinical grounds cow's milk (CM) protein sensitivity may be suspected. Here, using rectal protein challenge, we investigated the local inflammatory reaction to gluten and CM protein in adult patients with CD in remission. Rectal challenges with wheat gluten and dried CM powder were performed in 20 patients with CD and 15 healthy controls. Fifteen hours after challenge the mucosal reaction was recorded by the mucosal patch technique with measurements of local release of neutrophil and eosinophil granule constituents; myeloperoxidase (MPO) and eosinophil cationic protein (ECP). We measured the mucosal production of nitric oxide (NO) simultaneously. Six of the patients who reacted to CM were also challenged with alpha-lactalbumin and casein. In 18 of 20 patients gluten challenge induced neutrophil activation defined as increased MPO release and increased NO synthesis. Ten of these 20 patients showed a similarly strong inflammatory reaction to CM challenge. Six of the CM sensitive patients were challenged with specific CM proteins: casein and alpha-lactalbumin. Casein, in contrast to alpha-lactalbumin, induced an inflammatory response similar to that produced by CM. A mucosal inflammatory response similar to that elicited by gluten was produced by CM protein in about 50% of the patients with coeliac disease. Casein, in particular, seems to be involved in this reaction.
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Enfermedad Celíaca/etiología , Hipersensibilidad a la Leche/complicaciones , Proteínas de la Leche/inmunología , Administración Rectal , Adulto , Anciano , Animales , Caseínas/inmunología , Bovinos , Enfermedad Celíaca/inmunología , Femenino , Glútenes/administración & dosificación , Glútenes/inmunología , Humanos , Inmunidad Mucosa , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Mucosa Intestinal/inmunología , Lactalbúmina/inmunología , Masculino , Persona de Mediana Edad , Hipersensibilidad a la Leche/diagnóstico , Hipersensibilidad a la Leche/inmunología , Proteínas de la Leche/administración & dosificación , Óxido Nítrico/metabolismo , Peroxidasa/metabolismoRESUMEN
BACKGROUND AND AIMS: Patients with rheumatoid arthritis (RA) often feel there is an association between food intake and rheumatoid disease severity. To investigate a putative immunological link between gut immunity and RA, food antibodies were measured in serum and perfusion fluid from the jejunum of RA patients and healthy controls to determine the systemic and mucosal immune response. METHODS: IgG, IgA, and IgM antibodies to dietary antigens were measured in serum and jejunal perfusion fluid from 14 RA patients and 20 healthy subjects. The antigens originated from cow's milk (alpha-lactalbumin, beta-lactoglobulin, casein), cereals, hen's egg (ovalbumin), cod fish, and pork meat. RESULTS: In intestinal fluid of many RA patients, all three immunoglobulin classes showed increased food specific activities. Except for IgM activity against beta-lactoglobulin, all other IgM activities were significantly increased irrespective of the total IgM level. The RA associated serum IgM antibody responses were relatively much less pronounced. Compared with IgM, the intestinal IgA activities were less consistently raised, with no significant increase against gliadin and casein. Considerable cross reactivity of IgM and IgA antibodies was documented by absorption tests. Although intestinal IgG activity to food was quite low, it was nevertheless significantly increased against many antigens in RA patients. Three of the five RA patients treated with sulfasalazine for 16 weeks had initially raised levels of intestinal food antibodies; these became normalised after treatment, but clinical improvement was better reflected in a reduced erythrocyte sedimentation rate. CONCLUSIONS: The production of cross reactive antibodies is strikingly increased in the gut of many RA patients. Their food related problems might reflect an adverse additive effect of multiple modest hypersensitivity reactions mediated, for instance, by immune complexes promoting autoimmune reactions in the joints.
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Artritis Reumatoide/inmunología , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/etiología , Reacciones Cruzadas , Proteínas en la Dieta/inmunología , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Humanos , Inmunidad Mucosa , Inmunoglobulinas/análisis , Mucosa Intestinal/inmunología , Yeyuno/inmunología , Masculino , Persona de Mediana Edad , Sulfasalazina/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: To elucidate the dynamics of nitric oxide (NO) production induced by rectal gluten challenge and the relation between NO production and mucosal granulocyte activation. SUBJECTS AND METHODS: Release of rectal NO was measured in 13 patients with coeliac disease and in 18 controls before and after rectal wheat gluten challenge. Rectal gas was collected with a rectal balloon using a newly developed instrument/technique, the "mucosal patch technique". The instrument allows simultaneous measurements of concentrations of granulocyte mediators in the rectal mucosa. We measured myeloperoxidase (MPO), eosinophil cationic protein (ECP), and histamine. For comparison, we made similar measurements after corn (maize) gluten challenge. RESULTS: In all coeliac patients rectal NO concentration increased after gluten challenge and reached a peak after 15 hours (mean 9464 (SEM 2393) parts per billion (ppb); range 250-24982). The maximum MPO and ECP increase occurred five hours after challenge. A correlation was found between mucosal MPO and NO production at 15 hours. Six of the patients showed an increase in NO production 15 hours after rectal corn gluten challenge but this was much smaller than after gluten challenge. No increases were seen in the control group after either challenge. CONCLUSION: Mucosal activation of neutrophils and eosinophils precedes pronounced enhancement of mucosal NO production after rectal wheat gluten challenge in patients with coeliac disease. Some of our coeliac patients displayed signs of an inflammatory reaction, as measured by NO and granulocyte markers, after rectal corn gluten challenge.
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Enfermedad Celíaca/metabolismo , Glútenes/farmacología , Óxido Nítrico/metabolismo , Recto/metabolismo , Administración Rectal , Adulto , Anciano , Análisis de Varianza , Estudios de Casos y Controles , Proteína Catiónica del Eosinófilo/metabolismo , Eosinófilos/metabolismo , Femenino , Glútenes/administración & dosificación , Histamina/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Peroxidasa/metabolismo , Zea maysRESUMEN
BACKGROUND AND AIMS: There is a clear need for a rapid, simple, safe, and sensitive method of determining the type and intensity of inflammation in the gut mucosa in clinical practice. In this study, we have evaluated the potential of a new method, the mucosal patch technique, in patients with and without apparent gut inflammation, as assessed by conventional diagnostic procedures. SUBJECTS AND METHODS: The technique tested is based on the idea that inflammatory mediators released from the rectal mucosa can be absorbed by and then extracted from cellulose patches brought into contact with the mucosa by use of an instrument with an inflatable balloon. Measurements were performed in healthy controls (n = 16) and in patients with active (n = 19) and inactive ulcerative colitis (UC, n = 8), collagen colitis (CC, n = 12), coeliac disease (n = 13), and irritable bowel syndrome (IBS, n = 13). RESULTS: Inflammatory mediators from neutrophils (myeloperoxidase (MPO)) and eosinophils (eosinophil cationic protein (ECP)) were increased on average 300- and 10-fold, respectively, in patients with active UC compared with healthy controls and were correlated with the endoscopic score. Patients with inactive UC, CC, coeliac disease, and IBS exhibited no endoscopic signs of inflammation. These patient groups had significantly lower levels of MPO and ECP than the active UC group but showed on average a four- to sevenfold increase in MPO compared with healthy controls. CONCLUSION: The mucosal patch technique was well tolerated by patients and easily applied by the investigator. Pronounced neutrophil and eosinophil involvement in UC was demonstrated. With the high sensitivity of the technique, low degree mucosal neutrophil activation could also be quantified in patients with CC and UC in clinical remission. The finding of increased neutrophil involvement in patients with IBS contributes to the pathophysiological ideas of this disease.
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Eosinófilos/patología , Enfermedades Inflamatorias del Intestino/diagnóstico , Mucosa Intestinal/patología , Síndrome del Colon Irritable/diagnóstico , Activación Neutrófila , Adulto , Biomarcadores/análisis , Proteína Catiónica del Eosinófilo/análisis , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/patología , Síndrome del Colon Irritable/metabolismo , Síndrome del Colon Irritable/patología , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Peroxidasa/análisis , Recto/metabolismo , Manejo de Especímenes/instrumentación , Manejo de Especímenes/métodosRESUMEN
OBJECTIVES: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. METHODS: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. RESULTS: There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p<0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. CONCLUSIONS: The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment.
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Antiinflamatorios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Budesonida/uso terapéutico , Prednisolona/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antirreumáticos/uso terapéutico , Artritis Reumatoide/patología , Budesonida/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisolona/efectos adversos , Calidad de Vida , Resultado del TratamientoRESUMEN
OBJECTIVES: To evaluate the possible effect of androgen status on sexuality and mental wellbeing in patients with primary Sjögren's syndrome (pSS). METHODS: Serum levels of dehydroepiandrosterone sulphate (DHEA-S), testosterone (T), androstenedione, sex hormone binding globulin (SHBG), and the SHBG/T ratio were measured in 21 women with pSS. Sexual life was assessed by a Swedish version of the McCoy scale, which covers sexual experience and responsiveness during the past 30 days. A standardised questionnaire, the Psychological General Well-Being Index (PGWB), was used to examine quality of life and psychological symptoms in patients with pSS. RESULTS: Positive correlations were found between DHEA-S serum levels and the total McCoy score (r(s)=0.62; p<0.01), as well as the subscales of this score reflecting arousal (0.59; p<0.05), desire (r(s)=0.52; p<0.05), and satisfaction (r(s)=0.66; p<0.01). Serum DHEA-S concentrations were also related to the total PGWB score (r(s)=0.60; p<0.01) and subscales of this score: depression (r(s)=0.62; p<0.01), wellbeing (r(s)=0.64; p<0.01), general health (r(s)=0.67; p<0.01), and self control (r(s)=0.67; p<0.01). Total McCoy and PGWB scores and their subscales were not related to the serum levels of testosterone and androstenedione or the T/SHBG ratio. CONCLUSIONS: Circulating levels of the weak androgen DHEA-S are positively related to the quality of sexual life and mental wellbeing in women with pSS.
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Sulfato de Deshidroepiandrosterona/sangre , Calidad de Vida , Conducta Sexual , Síndrome de Sjögren/sangre , Síndrome de Sjögren/psicología , Adulto , Anciano , Androstenodiona/sangre , Femenino , Humanos , Trastornos Mentales/sangre , Trastornos Mentales/etiología , Persona de Mediana Edad , Psicometría , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangreRESUMEN
The aim of this in-vivo perfusion study in humans was to investigate the influence of a penetration enhancer, sodium caprate, on the rectal absorption of phenoxymethylpenicillin and antipyrine. Six subjects, 3 male and 3 female, were included in two separate studies using perfusion solution of different pH (T1 and T2, respectively). Each in-vivo rectal perfusion investigation lasted for 200 min and consisted of two periods of 100 min, the first serving as a control, and sodium caprate being added in the second period in both T1 and T2. The concentrations of phenoxymethylpenicillin, antipyrine and sodium caprate in the outlet perfusate were assayed by HPLC, as was the plasma concentrations of phenoxymethylpenicillin. At pH 6.0 (0-100 min) the fraction absorbed (f(abs)) and effective permeability (P(eff)) of phenoxymethylpenicillin were 0.3% and 0.06 x 4 cm s(-1), respectively, and remained unaffected by the addition of sodium caprate. When the same subjects were perfused at pH 7.4, the f(abs) and P(eff) of phenoxymethylpenicillin were 2.4% and 0.11 x 10(-4) cm s(-1) (0-100 min), respectively, also remaining unchanged by addition of sodium caprate (100-200 min). It was possible to determine the plasma AUC of phenoxymethylpenicillin after addition of sodium caprate in three subjects at both pHs; this was in the range of 14.0-62.8 and 56.4-231 (min micromol L(-1)) at pH 6.0 and 7.4, respectively. Interestingly, there was a correlation between P(eff) for sodium caprate and the individual plasma AUC and C(max) of phenoxymethyl-penicillin, which indicates that the permeability of the enhancer in the tissue upon which it should act is crucial for achieving an effect. The f(abs) and the P(eff) of antipyrine were not affected at either pH when sodium caprate was added to the perfusion solution. In conclusion, the plasma pharmacokinetics of phenoxymethylpenicillin suggested a slightly increased rectal absorption at pH 7.4 in subjects where sodium caprate was transported into the rectal tissue. However, the increased P(eff) for phenoxymethylpenicillin wastoo small to detectfrom the outlet perfusate, which suggests that sodium caprate alone has a limited effect on the permeability in-vivo across the rectal epithelium when it is presented in a solution.
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Ácidos Decanoicos/farmacología , Absorción Intestinal/efectos de los fármacos , Penicilina V/farmacocinética , Penicilinas/farmacología , Recto/metabolismo , Administración Rectal , Antiinflamatorios no Esteroideos/farmacocinética , Antipirina/farmacocinética , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Femenino , Humanos , Concentración de Iones de Hidrógeno , Mucosa Intestinal/metabolismo , Masculino , Penicilina V/sangre , Perfusión/instrumentación , PermeabilidadRESUMEN
BACKGROUND AND AIM: Accumulation and infiltration by neutrophil granulocytes is a prominent feature in the local inflammatory process in ulcerative colitis (UC). The present study was performed to evaluate human neutrophil lipocalin (HNL) as a specific neutrophil marker in the inflamed lesions of the colon and rectum in patients with colitis and proctitis. METHODS: The activity of intestinal neutrophils with respect to release of granule proteins was studied in 18 patients with UC (10 with colitis and eight with isolated proctitis) and in 18 healthy controls using perfusion fluid and biopsies from the sigmoid colon and rectum. The released amounts of the neutrophil granule proteins HNL and myeloperoxidase (MPO) were determined by radioimmunoassays, and the location of HNL and MPO in biopsies from colonic mucosa was examined by immunohistochemistry. RESULTS: Mucosal release of HNL and MPO was increased 10-55-fold in patients with colitis and proctitis compared with controls. Their bowel biopsies demonstrated that only neutrophils were stained with anti-HNL. We also found correlations between HNL and levels of granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 8 (IL-8) in perfusion fluids from the sigmoidal segments of patients with proctitis, between HNL and GM-CSF in rectal segments in patients with proctitis, and in sigmoidal segments in patients with colitis. CONCLUSION: We conclude that the increased release of HNL and MPO in colorectal perfusion fluids indicates neutrophil involvement in the local inflammatory process, and suggest that HNL may serve as a specific marker of intestinal neutrophil activation in UC. GM-CSF, and to some extent IL-8, may play a role in neutrophil accumulation and priming in this disease.
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Proteínas de Fase Aguda , Proteínas Portadoras/metabolismo , Colitis Ulcerosa/metabolismo , Neutrófilos/metabolismo , Proteínas Oncogénicas , Proctitis/metabolismo , Adulto , Anciano , Biomarcadores , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Humanos , Inmunohistoquímica , Interleucina-8/metabolismo , Mucosa Intestinal , Lipocalina 2 , Lipocalinas , Masculino , Persona de Mediana Edad , Peroxidasa/metabolismo , Proteínas Proto-OncogénicasAsunto(s)
Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/fisiopatología , Trasplante de Corazón/fisiología , Hialuronoglucosaminidasa/uso terapéutico , Animales , Hialuronoglucosaminidasa/administración & dosificación , Infusiones Intravenosas , Presión , Ratas , Ratas Endogámicas , Ratas Endogámicas WKY , Factores de Tiempo , Trasplante Homólogo , Trasplante IsogénicoRESUMEN
OBJECTIVE: To assess the hypothalamic-pituitary-adrenal (HPA) and thyroid axes in women with primary Sjögren's syndrome (pSS). METHODS: In 10 women with pSS and 10 age matched female controls, we evaluated serum dehydroepiandrosterone sulfate (DHEA-S), testosterone, androstenedione, follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone, prolactin, growth hormone, sex hormone binding globulin, cortisol, and adrenocorticotropin hormone (ACTH), in both basal condition and after stimulation with corticotropin releasing hormone, thyrotropin releasing hormone, and luteinizing hormone releasing hormone intravenously. Patients had not previously been treated with glucocorticoids. RESULTS: Patients with pSS had significantly lower basal mean DHEA-S values compared with healthy controls (2.4 +/- 0.4 vs 3.9 +/- 0.3 mumol/l; p < 0.05) and significantly lower DHEA-S values after stimulation. The cortisol/DHEA-S ratio in the patient group was higher than in controls (171 +/- 39 vs 76 +/- 5; p < 0.05). A correlation was found between basal ACTH and DHEA-S values in the patients (r = 0.650; p = 0.05). No correlation was seen between disease activity or age and the serum concentration of DHEA-S. The levels of other hormones both at baseline and after stimulation were similar in patients and controls. CONCLUSION: The results show that women with pSS have intact cortisol synthesis but decreased serum concentrations of DHEA-S and increased cortisol/DHEA-S ratio compared with healthy controls. The findings may reflect a constitutional or disease mediated influence on adrenal steroid synthesis. The thyroid axis and gonadotropin secretion were similar in patients and controls.
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Sulfato de Deshidroepiandrosterona/sangre , Sistema Hipotálamo-Hipofisario/fisiopatología , Sistema Hipófiso-Suprarrenal/fisiopatología , Síndrome de Sjögren/sangre , Síndrome de Sjögren/fisiopatología , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Androstenodiona/sangre , Femenino , Hormona Folículo Estimulante/sangre , Hormona de Crecimiento Humana/sangre , Humanos , Hidrocortisona/sangre , Hormona Luteinizante/sangre , Persona de Mediana Edad , Prolactina/sangre , Globulina de Unión a Hormona Sexual/metabolismo , Testosterona/sangreRESUMEN
Our previous studies have suggested a role for renomedullary interstitial cells (RMICs) and renal medullary hyaluronan (HA) in water homeostasis. In the present study, cultured rat RMICs were used to examine the relationship of osmolality and oxygen tension on the extracellular amount of HA in the culture and to the cellular immunoreactivity to CD44, a HA binding protein. Under isotonic (330 mOsm(.)kg(-1) H(2)O), normoxic (20% O(2)) conditions, supernatant from sub-confluent RMICs contained 120+/-37 pg 10(4) cells(-1) 24 h(-1) of HA. Under hyperosmotic conditions (630 mOsm kg(-1) H(2)O), HA in the supernatant was decreased by 42% and under hypoosmotic conditions (230 mOsm kg(-1) H(2)O) it was doubled. Under hypoxic, iso-osmolar conditions (5% and 1% O(2), 330 mOsm kg(-1) H(2)O) this HA content was decreased by 56 and 48%, respectively, compared with normoxic, iso-osmolal conditions. Expression of CD44 on sub-confluent cells increased with increasing osmolality, as shown by immunostaining and flow cytometric analysis. The increases in CD44 from 330 to 630, 930 and 1230 mOsm kg(-1) H(2)O amounted to 5, 142 and 212%, respectively. Low oxygen tension (5% O(2)) decreased the intensity of CD44 immunofluorescence by 31%. Cell viability was similar at all conditions studied. In summary, these data indicate that cultured RMICs produce HA and are immunoreactive to CD44. In the supernatant of RMICs, the HA content decreases under hyperosmotic, hypoxic conditions. Conversely, CD44 immunoreactivity increases under hyperosmotic conditions. These results may explain our previous in vivo findings of a decreased renal papillary HA content during anti-diuresis and an increased content during water diuresis. The results support the concept that RMICs play an important role in renal water handling.
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Receptores de Hialuranos/metabolismo , Ácido Hialurónico/metabolismo , Riñón/metabolismo , Oxígeno/metabolismo , Animales , Células Cultivadas , Medios de Cultivo , Riñón/citología , Concentración Osmolar , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVES: To evaluate quality of life and psychological symptoms in patients with primary Sjögren's syndrome and to compare this with patients with rheumatoid arthritis. METHODS: A standardised questionnaire, the Psychological General Well-Being Index (PGWB), was used to examine the quality of life and psychological symptoms in patients with primary Sjögren's syndrome (pSS; n = 34). Patients with rheumatoid arthritis (RA; n = 32) were used as patient controls. RESULTS: The total mean score +/- SD for PGWB was 84.9 +/- 16.2 in pSS patients and significantly lower (p = 0.001) than in RA patients (97.7 +/- 17.5). Patients with pSS had an increased propensity for depressed mood (p = 0.0009), and suffered from reduced well-being (p = 0.002) and impaired vitality (p = 0.003). CONCLUSION: The results suggest that patients with pSS have a reduced quality of life, a higher degree of distress and a lower sense of well-being than patients with RA.
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Salud Mental , Calidad de Vida , Síndrome de Sjögren/psicología , Adulto , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/psicología , Depresión/etiología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Growing evidence suggests that the interstitial hyaluronan (HA) content is a determinant of the fluid exchange barrier in tissues through its high resistance to water flow. This study addressed the possible involvement of renal papillary HA in water balance regulation. METHODS: In anesthetized rats during different states of renal water handling (euvolemia, water diuresis, antidiuresis), in desert rodents, and in Brattleboro rats (diabetes insipidus) with a hereditary difference in water handling, regional renal HA and water contents were measured. RESULTS: The intrarenal HA distribution is heterogeneous, with 100 times larger amounts in the papilla than in the cortex. Compared with control rats, two hours of water diuresis increased the papillary HA content by 48% and that in the outer medulla by 52%, leaving the cortex unaffected. After 24 hours of water deprivation, papillary HA was decreased by 17%, while outer medullary HA remained unchanged. In gerbils, papillary and outer medullary HA contents were only 25 and 13%, respectively, of those in normal rats, while the cortical content was similar. In Brattleboro rats, the outer medullary HA content was significantly higher (285%) than in the normal rat, while the papillary content was similar. Generally, papillary HA was positively correlated to water content but was inversely related to urine osmolality. CONCLUSIONS: The amount of renal papillary HA changes in response to water balance of the organism. When excess water needs to be excreted, increased papillary interstitial HA could antagonize water reabsorption. The opposite occurs during water conservation. HA may play a role in renal water handling by affecting physicochemical characteristics of the papillary interstitial matrix and influencing the interstitial hydrostatic pressure, thereby determining interstitial water diffusion.
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Agua Corporal/metabolismo , Ácido Hialurónico/metabolismo , Riñón/metabolismo , Animales , Desamino Arginina Vasopresina/farmacología , Diabetes Insípida/metabolismo , Diuresis , Gerbillinae , Masculino , Ratas , Ratas Brattleboro , Ratas Sprague-Dawley , Valores de Referencia , Fármacos Renales/farmacología , Privación de Agua/fisiologíaRESUMEN
BACKGROUND: Basic fibroblast growth factor (bFGF) promotes angiogenesis and several other biologic processes, including proliferation of mesenchymal cells and tumor progression. We investigated whether bFGF could be detected in the intraluminal secretion of the small intestine, sigmoid colon, and rectum in healthy individuals and in patients with ulcerative colitis. METHODS: We used endoscopic perfusion techniques to obtain samples from well-defined intestinal segments. The perfusion fluid concentrations of bFGF, biochemical markers of inflammation, myeloperoxidase (MPO), interleukin-6 (IL-6), and permeability (albumin) were determined with immunochemical methods. RESULTS: In the perfusion fluids the albumin concentration, which reflects passive diffusion, was less than 1% of the plasma concentration, whereas the intestinal concentration of bFGF was similar to that in plasma. Among healthy subjects the concentration of bFGF was eightfold higher in the jejunum and twofold higher in the rectum than in the sigmoid colon. The perfusion fluid from colorectal segments in patients with ulcerative colitis had a significantly higher mean concentration of bFGF than that from healthy individuals; an almost 10-fold difference was found in rectal segments. There were strong correlations between the concentration of bFGF and the concentrations of MPO and IL-6. CONCLUSIONS: The high concentrations of bFGF in the intestinal perfusion fluid reflect either a local synthesis or an active secretion of bFGF within the mucosa. The bFGF concentration differs in intestinal anatomic location and increases significantly in patients with ulcerative colitis in close relationship with biochemical markers of inflammation and permeability.
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Colitis Ulcerosa/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Mucosa Intestinal/metabolismo , Adulto , Albúminas/metabolismo , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Técnicas para Inmunoenzimas , Interleucina-6/metabolismo , Masculino , Perfusión , Peroxidasa/metabolismo , Radioinmunoensayo , Análisis de RegresiónRESUMEN
BACKGROUND: The connective tissue component hyaluronan is accumulated locally in the damaged tissue during various inflammatory conditions. Owing to the strong water-binding capacity of this glycosaminoglycan, increased tissue content of hyaluronan is paralleled by the development of interstitial edema. The aim with the current experiment was to investigate whether hyaluronan is accumulated in acute pancreatitis and if increased levels of hyaluronan can be correlated to the inflammation of the pancreatic tissue. METHODS: Acute pancreatitis was induced in Sprague-Dawley rats by the administration of supramaximal doses of the cholecystokinin analogue caerulein. The animals were followed for 5 hours (n = 4), 24 hours (n = 6), or 48 hours (n = 5), and the pancreata were then investigated for hyaluronan and water content, hyaluronan distribution, general morphology and the presence of CD44-positive cells, macrophages, and T lymphocytes. RESULTS: Hyaluronan accumulated in the edematous interstitium during acute pancreatitis. Twenty-four hours after the induction of pancreatitis, the hyaluronan content of the pancreata had increased by more than 100%. Simultaneously, CD44-positive cells infiltrated the tissue. However, no correlation between hyaluronan and water was seen at any time point. CONCLUSIONS: This study shows that acute pancreatitis is associated with a strong but transient increase in interstitial hyaluronan and an infiltration of CD44-positive cells located mainly in the same region as the accumulated hyaluronan.
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Ácido Hialurónico/metabolismo , Pancreatitis/etiología , Pancreatitis/metabolismo , Enfermedad Aguda , Amilasas/sangre , Animales , Ceruletida/toxicidad , Edema/metabolismo , Hialuronoglucosaminidasa/farmacología , Masculino , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Pancreatitis/patología , Ratas , Ratas Sprague-Dawley , Agua/metabolismoRESUMEN
OBJECTIVE: To examine the degree of anxiety and depression and to assess well being and general symptoms in patients with primary Sjögren's syndrome (SS). METHODS: A standardized questionnaire, the Hospital Anxiety and Depression Scale, was used to examine the degree of anxiety and depression in patients with primary SS (n = 62) and in age matched healthy female controls. The Gothenburg quality of life instrument (GQOL) was used to assess well being and general symptoms. Patients with rheumatoid arthritis (RA; n = 38) were used as patient controls. RESULTS: The patients with primary SS had significantly higher scoring rate for "possible" clinical anxiety (48%) and for "possible" clinical depression (32%) compared with reference groups (p<0.05). The physical and mental well being of the patients with primary SS were significantly reduced compared with controls. Furthermore, patients with primary SS complained more commonly of low mood, irritability, headache, gastrointestinal symptoms, and impaired concentration and memory than the patients with RA. CONCLUSION: The results indicate that patients with primary SS often have psychiatric symptoms and worse well being, which may affect their quality of life.
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Ansiedad/etiología , Depresión/etiología , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/psicología , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/diagnóstico , Ansiedad/epidemiología , Depresión/diagnóstico , Depresión/epidemiología , Femenino , Humanos , Masculino , Escala de Ansiedad Manifiesta , Persona de Mediana Edad , Calidad de VidaRESUMEN
BACKGROUND: Treatment with the hyaluronan-degrading enzyme, hyaluronidase, reduces rejection-induced interstitial edema of transplanted organs. Hyaluronidase has also been demonstrated to reduce tissue necrosis after experimentally induced myocardial infarction, but its clinical use has been limited by an observed interaction between heparin and hyaluronan. In the present work, we investigated whether it is also possible to retain the effect of the enzyme in heparinized animals. METHODS: Day 5 after heterotopic heart transplantation, recipient rats received a 2-hour intravenous infusion of hyaluronidase, either of ovine or of bovine origin. Concomitantly, the animals received intravenous heparin, either as 2 bolus doses or as a constant infusion. RESULTS: Both hyaluronidase preparations effective reduced the hyaluronan content as well as the water content of the rejecting cardiac grafts. The concomitant use of heparin did not hamper the positive results, neither when heparin was administered intermittently nor when it was given continuously. CONCLUSIONS: Our results in the transplantation model clearly demonstrate that hyaluronidase can be successfully used in heparinized individuals, provided that sufficient doses of the enzyme are given.