Rheumatoid arthritis and the Th1 chemokine MIG.

Monokine induced by interferon (IFN)-γ (MIG) and its receptor chemokine (C-X-C motif) receptor 3 (CXCR)3 seem to play an important role in the pathogenesis of rheumatoid arthritis (RA). MIG expression has been observed in sera, synovial fluid (SF) and synovial tissue of RA patients; it is highly expressed in RA synovium by infiltrating macrophage-like cells and fibroblast-like synoviocytes. A Type-1 helper-response orientated disease was suggested because of the high expression of CXCR3 in SF T cells and the presence of elevated IFN-γ levels. It has been observed a decrease of the inflammation by anti-CXCR3, and anti-MIG molecules, in fact they inhibit CXCR3-enhanced cell migration and pro-inflammatory cytokine expression, leading to an amelioration of the arthritis progression. These findings suggest a possible therapeutic role of these molecules in humans.

The MIG Chemokine in Inflammatory Myopathies.

The chemokine monokine induced by interferon (IFN)-γ (MIG) is expressed in idiopathic inflammatory myopathies muscle. Abundant expression of MIG was observed on macrophages and T cells surrounding and invading non-necrotic muscle fibers in polymyositis and in inclusion-body myositis and in T cells in perimysial infiltrates of dermatomyositis. MIG is also localized to blood vessel endothelial cells in all inflammatory and normal muscle tissues and it exerts its biological effects mainly via binding to the chemokine (C-X-C motif) receptor (CXCR)3. Serum MIG is high in patients with inflammatory myopathies. Human skeletal muscle cells might actively self-promote muscular inflammation by eliciting MIG secretion, under the influence of cytokines (IFN-γ, tumor necrosis factor-α), which can amplify Th1 cell tissue infiltration in vivo. It has been shown that drugs able to block the MIG/CXCR3 axis can suppress inflammation in muscle.

MRI assessment of the postprandial gastrointestinal motility and peptide response in healthy humans.

BACKGROUND: Feeding triggers inter-related gastrointestinal (GI) motor, peptide and appetite responses. These are rarely studied together due to methodological limitations. Recent MRI advances allow pan-intestinal, non-invasive assessment of motility in the undisturbed gut. This study aimed to develop a methodology to assess pan-intestinal motility and transit in a single session using MRI and compare imaging findings to GI peptide responses to a test meal and symptoms in a healthy volunteer cohort. METHODS: Fifteen healthy volunteers (29.3±2.7 years and BMI 20.1±1.2 kg m-2 ) underwent baseline and postprandial MRI scans, symptom questionnaires, and blood sampling (for subsequent GI peptide analysis, Glucagon-like peptide-1 [GLP-1], Polypeptide YY [PYY], Cholecystokinin [CCK]) at intervals for 270 minutes following a 400 g soup meal (204 kcal, Heinz, UK). Gastric volume, gall bladder volume, small bowel water content, small bowel motility, and whole gut transit were measured from the MRI scans. KEY RESULTS: (mean±SEM) Small bowel motility index increased from fasting 39±3 arbitrary units (a.u.) to a maximum of 87±7 a.u. immediately after feeding. PYY increased from fasting 98±10 pg mL-1 to 149±14 pg mL-1 at 30 minutes and GLP-1 from fasting 15±3 µg mL-1 to 22±4 µg mL-1 . CCK increased from fasting 0.40±0.06 pmol mL-1 to 0.94±0.1 pmol mL-1 . Gastric volumes declined with a T1/2 of 46±5 minute and the gallbladder contracted from a fasting volume of 19±2 mL-1 to 12±2 mL-1 . Small bowel water content increased from 39±2 mL-1 to 51±2 mL-1 postprandial. Fullness VAS score increased from 9±5 mm to 41±6 mm at 30 minutes postprandial. CONCLUSIONS AND INFERENCES: The test meal challenge was effective in inducing a change in MRI motility end-points which will improve understanding of the pathophysiological postprandial GI response.

Bladder cancer and Th1 chemokines

Bladder cancer arises from the epithelial lining of the urinary bladder, and it is known as transitional cell carcinoma (TCC). Tobacco smoking is the main known contributor to urinary bladder cancer. However thirty percent of bladder tumors probably result from occupational exposure in the workplace to carcinogens. Immunotherapy by intravesicular delivery of Bacillus Calmette­Guérin (BCG) is used to treat and prevent the recurrence of superficial bladder cancer. Successful BCG immunotherapy for bladder cancer is associated with proper induction of T helper (Th)1 immunity. In bladder cancer patients after intravesicular BCG, urine was found to contain high levels of IP-10, and Interferon (IFN)-γ. TCC and endothelial cell lines were able to secrete IP-10 in response to BCG or IFN stimulation in vitro. Furthermore intravesicular BCG induces a cytokine-rich urinary microenvironment that is inhibitory to human endothelial cells and it is anti-angiogenetic by the induction of Th1 chemokines. Other studies suggest that therapeutic strategies involving Th1 induction and Th2 dampening may improve responses to immunotherapy. Further studies are needed to evaluate the IP-10 in circulation, and urine, as prognostic marker of bladder cancer patients, also in relation to BCG immunotherapy

High IgE levels in patients affected by psoriasis: review of the literature and personal observations.

OBJECTIVE: The concomitance of psoriasis and high IgE levels in the same patient, possibly associated to allergies, should not come as a surprise anymore, because both diseases are characterised by an immunological disorder, involving cytokines and other inflammatory mediators, with massive activation of the cell-mediated immunity. MATERIALS AND METHODS: During a period of 18 months, using a radio-immunologic method, we assessed the level of IgE in patients with severe psoriasis who were not responding to the common therapy. RESULTS: Patients with severe psoriasis had high levels of IgE. CONCLUSIONS: IgEs have an important role in pathogenesis of psoriasis and atopic dermatitis, but the mechanism is not yet clear.

Anti-neutrophil cytoplasmic antibodies in echinococcus granulosus hydatid disease.

The authors studied the presence of ANCA, evaluated by indirect immunofluorescence (IIF) and ELISA for anti-lactoferrin (LF), and anti-myeloperoxidase antibodies (anti-MPO), in sera of 69 patients with cystic echinococcosis (CE). According to Caremani's classification, 27 patients were considered to have active cysts and 42 patients were considered to have inactive cysts. ANCA were detected in 9 out of 27 patients (33.3%) with active cysts and in 3 out of 42 patients (7.1%) with inactive cysts. Differences between the two groups were statistically significant (P < 0.05). Anti-LF antibodies were found in seven patients (10.14%) and anti-MPO antibodies in ten patients (14.5%).

[ANP in the cirrhotic patient. A clinical contribution]. / L'ANP nel paziente cirrotico. Contributo clinico.

Pathogenesis of ascites in patients affected by liver cirrhosis is still debated; humoral and haemodynamic factors can play a role. Plasmatic renin activity (PRA), plasmatic aldosterone (PA), atrial natriuretic peptide (ANP) plasma levels, blood Na, K, urea, urinary K and Na were evaluated in 14 patients affected by liver cirrhosis (11 males and 3 females, aged from 38 to 62 years), 8 of them with ascites. The results were compared with those obtained in a control group poised to age and sex to the experimental group. 4 out of 14 patients suffering from ascites unresponsive to medical treatment were submitted to peritoneal venous jugular shunt (PVGS) and blood samples for PRA, PA and ANP were withdrawn immediately before, 4, 8 hours following surgery. The patients affected by liver cirrhosis without ascites showed PRA and PA levels similar to those observed in the control group, while ANP plasma levels were significantly higher (50.6 + 9.6 vs. 39.7 + 9.5 Pg/ml) (p < 0.02). In patients with ascites ANP, PA and PRA levels were higher than those observed in non ascites patients (ANP = 147.8 + 97.3 vs. 50.6 + 9.6 pg/ml; PA = 20.6 + 2.7 vs 7.8 + 0.8 ng/dl; PRA = 4.48 + 0.5 vs 1.9 + 0.34 ng/ml/h). In patients submitted to PVGS, PA and PRA levels were reduced 4 and 8 hours following the surgery, while ANP levels showed significant increase. A natriuretic and diuretic response has been observed even in the absence of ANP plasma levels variations.(ABSTRACT TRUNCATED AT 250 WORDS)

[The circulation of the hepatitis A and B viruses in the Somali population]. / Ricerche sulla circolazione del virus A e del virus B dell'epatite nella popolazione somala.

We report the results of a study carried out to evaluate the extent of hepatitis A virus (HAV) and hepatitis B virus (HBV) circulation in Somalia. Serum samples were collected from 593 subjects (age range 0-83 years) and tested for anti-hepatitis A (HAV) and anti-HAV IgM. Serum samples taken from 1272 individuals (age range 0-83 years) were tested for HBsAg, anti-HBsAg, anti-HBcAg, HBeAg and anti-HBeAg. We confirmed a very high rate of HAV exposure (about 90% of the subjects tested had circulating anti-HAV) as is typical of fecal-orally transmitted infectious agents. The age-specific anti-HAV IgM prevalence suggests that HAV infection is acquired very early in life. Our data also indicate a high rate of HBsAg carriers (range: 10.5%-27.4%) in the Somalian population. When all markers are considered, 60% of the adult population showed evidence of HBV exposure. HBV spreads very subtly: in fact, it is generally transmitted via non-overtly percutaneous routes. In Somalia, hepatitis A virus infection is highly endemic and occurs very early in life. Hepatitis B virus infection is also widespread in this country.

Basophil releasability in human hydatidosis.

We studied immunoglobulin E (IgE)- and non-IgE-mediated releasability in basophils from 31 patients with hydatidosis. Histamine release to non-IgE-dependent stimuli did not differ significantly between normal individuals and patients with hydatidosis. On the contrary, an increased histamine liberation was obtained by challenging basophils from hydatid patients with anti-human IgE. It is concluded that Echinococcus granulosus infection induces an enhanced sensitivity of basophils to IgE-dependent stimuli.

A new serological technique, time-resolved fluoroimmunoassay (TRFIA), for the immunological diagnosis of urinary schistosomiasis.

The application of a new serological method, time-resolved fluoroimmunoassay (TRFIA), is described for the diagnosis of urinary schistosomiasis. A chelate of lanthanides (europium) with a long fluorescent life-time is used as label. The intensity of fluorescence is measured after a delay selected to eliminate almost completely the background fluorescence, which decays rapidly. TRFIA was compared with an established method, enzyme linked immunosorbent assay (ELISA). Using sera from proven cases of Schistosoma haematobium infection, 98.1% of the samples were positive by TRFIA and 86.5% by ELISA. Sera from patients infected with helminths other than schistosomes produced only 1.5% of false positives with TRFIA, compared with 12.3% by ELISA. TRFIA is more sensitive and specific than ELISA.