Prognostic value of plasma pentraxin 3 levels in patients with septic shock admitted to intensive care.

OBJECTIVE: To evaluate the usefulness of a new marker, pentraxin, as a prognostic marker in septic shock patients. MATERIALS AND METHODS: Single-centre prospective observational study that included all consecutive patients 18 years or older who were admitted to the intensive care unit (ICU) with septic shock. Serum levels of procalcitonin (PCT), C-reactive protein (CRP) and pentraxin (PTX3) were measured on ICU admission. RESULTS: Seventy-five septic shock patients were included in the study. The best predictors of in-hospital mortality were the severity scores: SAPS II (AUC = 0.81), SOFA (AUC = 0.79) and APACHE II (AUC = 0.73). The ROC curve for PTX3 (ng/mL) yielded an AUC of 0.70, higher than the AUC for PCT (0.43) and CRP (0.48), but lower than lactate (0.79). Adding PTX3 to the logistic model increased the predictive capacity in relation to SAPS II, SOFA and APACHE II for in-hospital mortality (AUC 0.814, 0.795, and 0.741, respectively). In crude regression models, significant associations were found between in-hospital mortality and PTX3. This positive association increased after adjusting for age, sex and immunosuppression: adjusted OR T3 for PTX3 = 7.83, 95% CI 1.35-45.49, linear P trend = 0.024. CONCLUSION: Our results support the prognostic value of a single determination of plasma PTX3 as a predictor of hospital mortality in septic shock patients.

Insulin resistance in non-diabetes patients with spondyloarthritis.

Objectives: Insulin resistance (IR) constitutes a major underlying abnormality driving cardiovascular disease in the general population and has been linked to inflammatory diseases. In this study, we aimed to determine the prevalence of IR in patients with spondyloarthritis (SpA) and whether IR can be explained by disease-related features in such cases. Method: The study included 577 subjects: 306 patients diagnosed with SpA according to Assessment of SpondyloArthritis international Society criteria and 271 controls. Insulin and C-peptide serum levels, IR and ß-cell function (%B) indices by homoeostatic model assessment (HOMA2), and lipid profiles were assessed in patients and controls. A multivariable regression analysis was performed to evaluate the differences in IR indices between patients and controls and to determine how IR is associated with disease-related characteristics in SpA patients. Results: HOMA2-%B and HOMA2-IR scores, both calculated with insulin or C-peptide, had significantly higher values in SpA patients compared to controls in multivariable analysis adjusted for age, gender, traditional IR-related factors, and glucocorticoid intake. Disease activity, functional status, and metrological SpA indices were positively related to IR, but only in univariable analysis. Disease duration and positivity for human leucocyte antigen-B27 were independently associated with a higher HOMA2-%B after multivariable analysis. Conclusion: Patients with SpA have an increased IR compared to controls. SpA disease-related data are independently associated with ß-cell dysfunction.

Abnormal bone turnover in individuals with low serum alkaline phosphatase.

The clinical spectrum of hypophosphatasia (HPP) is broad and variable within families. Along severe infantile forms, adult forms with mild manifestations may be incidentally discovered by the presence of low alkaline phosphatase (ALP) activity in serum. However, it is still unclear whether individuals with persistently low levels of ALP, in the absence of overt manifestations of HPP, have subclinical abnormalities of bone remodeling or bone mass. The aim of this study was to obtain a better understanding of the skeletal phenotype of adults with low ALP by analyzing bone mineral density (BMD), bone microarchitecture (trabecular bone score, TBS), and bone turnover markers (P1NP and ß-crosslaps). We studied 42 individuals with persistently low serum ALP. They showed lower levels of P1NP (31.4 ± 13.7 versus 48.9 ± 24.4 ng/ml; p = 0.0002) and ß-crosslaps (0.21 ± 0.17 versus 0.34 ± 0.22 ng/ml, p = 0.0015) than individuals in the control group. There were no significant differences in BMD, bone mineral content, or TBS. These data suggest that individuals with hypophosphatasemia have an overall reduction of bone turnover, even in the absence of overt manifestations of HPP or low BMD. We evaluated bone mineral density (BMD), bone microarchitecture, and bone turnover markers in patients with low serum levels of alkaline phosphatase. Our results show that these patients have low bone remodeling even in the absence of BMD abnormalities, thus supporting the recommendation of avoiding antiresorptives such as bisphosphonates in these subjects.

Insulin resistance in hidradenitis suppurativa: a case-control study.

BACKGROUND: The association between chronic inflammatory diseases, such as rheumatoid arthritis and psoriasis, and insulin resistance (IR) has been well established. Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease that affects the apocrine gland-bearing areas of the body. OBJECTIVE: We aimed to determine the prevalence of IR in patients with HS. METHODS: This cross-sectional, case-control study enrolled 137 subjects, 76 patients with HS and 61 age- and gender-matched controls. Demographic data, clinical examination of HS patients, anthropometric measures, cardiovascular risk factors and laboratory studies were recorded. The homeostasis model assessment of IR (HOMA-IR) was calculated in all participants by measuring fasting plasma glucose and insulin levels. RESULTS: The median (IQR) HOMA-IR value in HS patients was significantly higher [2.0 (1.0-3.6)] than in controls [1.5 (0.9-2.3)] (P = 0.01). The prevalence of IR was significantly higher in cases (43.4%) compared with controls (16.4%) (P = 0.001). In the linear regression multivariable analysis after adjusting for age, sex and body mass index (BMI), HS remained as a significant factor for a higher HOMA-IR [2.51 (0.18) vs 1.92(0.21); P = 0.04]. The HOMA-IR value and the prevalence of IR did not differ significantly among HS patients grouped by severity of the disease. CONCLUSION: Our results show an increased frequency of IR in HS. Thus, we suggest HS patients to be evaluated for IR and managed accordingly.

Diverging results of areal and volumetric bone mineral density in Down syndrome.

Population with Down syndrome (DS) has lower areal BMD, in association with their smaller skeletal size. However, volumetric BMD and other indices of bone microarchitecture, such as trabecular bone score (TBS) and calcaneal ultrasound (QUS), were normal. INTRODUCTION: Patients with DS have a number of risk factors that could predispose them to osteoporosis. Several studies reported that people with DS also have lower areal bone mineral density, but differences in the skeletal size could bias the analysis. METHODS: Seventy-five patients with DS and 76 controls without intellectual disability were recruited. Controls were matched for age and sex. Bone mineral density (BMD) was measure by Dual-energy X-ray Absorptiometry (DXA), and volumetric bone mineral density (vBMD) was calculated by published formulas. Body composition was also measured by DXA. Microarchitecture was measured by TBS and QUS. Serum 25-hidroxyvitamin D (25OHD), parathyroid hormone (PTH), aminoterminal propeptide of type collagen (P1NP), and C-terminal telopeptide of type I collagen (CTX) were also determined. Physical activity was assessed by the International Physical Activity Questionnaires (IPAQ-short form). To evaluate nutritional intake, we recorded three consecutive days of food. RESULTS: DS individuals had lower height (151 ± 11 vs. 169 ± 9 cm). BMD was higher in the controls (lumbar spine (LS) 0.903 ± 0.124 g/cm2 in patients and 0.997 ± 0.115 g/cm2 in the controls; femoral neck (FN) 0.761 ± .126 g/cm2 and 0.838 ± 0.115 g/cm2, respectively). vBMD was similar in the DS group (LS 0.244 ± 0.124 g/cm3; FN 0.325 ± .0.073 g/cm3) and the controls (LS 0.255 ± 0.033 g/cm3; FN 0.309 ± 0.043 g/cm3). Microarchitecture measured by QUS was slightly better in DS, and TBS measures were similar in both groups. 25OHD, PTH, and CTX were similar in both groups. P1NP was higher in the DS group. Time spent on exercise was similar in both groups, but intensity was higher in the control group. Population with DS has correct nutrition. CONCLUSIONS: Areal BMD is reduced in DS, but it seems to be related to the smaller body and skeletal size. In fact, the estimated volumetric BMD is similar in patients with DS and in control individuals. Furthermore, people with DS have normal bone microarchitecture.

Anti-TNF-α therapy improves insulin sensitivity in non-diabetic patients with psoriasis: a 6-month prospective study.

OBJECTIVE: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular death. Several studies have shown a beneficial effect of anti-TNF-α therapy on the mechanisms associated with accelerated atherogenesis in patients with inflammatory arthritis, including an improvement of insulin sensitivity. In this study, we aimed to determine for the first time whether the anti-TNF-α monoclonal antibody adalimumab may improve insulin sensitivity in non-diabetic patients with psoriasis. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate to severe psoriasis seen at the Dermatology Division of Hospital Universitario Marques de Valdecilla (Northern Spain) who completed 6 months of therapy with adalimumab (80 mg at week 0 followed by 40 mg every other week, starting 1 week after the initial dose). Patients with chronic kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation including assessment of insulin sensitivity using the Quantitative Insulin Sensitivity Check Index (QUICKI) was performed at the onset of the treatment (time 0) and at month 6. RESULTS: Twenty-nine patients (52% women; 38.6 ± 10.7 years) with moderate to severe psoriasis [body surface area (BSA) 37.9 ± 16.3%], Psoriasis Area and Severity Index [(PASI) 18.9 ± 7.8] were assessed. Statistically significant improvement (P=0.008) of insulin sensitivity was observed after 6 months of adalimumab therapy (QUICKI at time 0: 0.35 ± 0.04 vs. 0.37 ± 0.04 at month 6). Significant improvement of erythrocyte sedimentation rate, ultrasensitive C-reactive protein, BSA, PASI, Nail Psoriasis Severity Index, physician global assessment and psoriatic arthritis screening and evaluation questionnaire was also observed at month 6 (P < 0.05 for each variable). CONCLUSION: Our results support a beneficial effect of the anti-TNF-α blockade on the mechanisms associated with accelerated atherogenesis in patients with psoriasis.

Visfatin is not associated with inflammation or metabolic syndrome in patients with severe rheumatoid arthritis undergoing anti-TNF-alpha therapy.

BACKGROUND AND OBJECTIVE: Visfatin is an insulin-mimetic adipokine. In non-rheumatoid arthritis (RA) patients circulating levels of visfatin are correlated with the amount of visceral fat. Recent studies have disclosed an implication of visfatin in inflammation. Chronic systemic inflammation is of major importance in the development of atherosclerosis in RA. In the present study we investigated whether inflammation, obesity or metabolic syndrome are potential determinants of circulating visfatin concentrations in a group of RA patients on periodical treatment with the TNF-alpha blocker infliximab due to severe disease. We also assessed whether the infusion of infliximab may alter circulating visfatin concentrations in patients with severe RA. METHODS: We investigated 33 non-diabetic patients with RA on periodical treatment with infliximab. Serum visfatin levels were determined immediately prior to and after infliximab infusion. RESULTS: There was no correlation between body mass index of RA patients and baseline serum level of visfatin. Also, no significant correlations between baseline visfatin levels and the age at the time of the study or at the onset of the disease, disease duration, ESR and CRP levels, DAS28, lipids, insulin sensitivity, resistin or the cumulative prednisone dose at the time of the study were found. Visfatin levels did not change upon infliximab infusion. CONCLUSIONS: In RA patients on TNF-alpha blocker treatment, circulating visfatin levels are unrelated to disease activity, adiposity or metabolic syndrome. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by changes in serum levels of visfatin.

Short-term effect of anti-TNF-alpha therapy on nitric oxide production in patients with severe rheumatoid arthritis.

OBJECTIVE: TNF-alpha increases expression of inducible nitric oxide synthase (iNOS) in macrophages and vascular endothelial cells. Under normal conditions, iNOS activity is very low. However, iNOS activity is stimulated during inflammation by cytokines such as TNF-alpha and the amount of NO produced by iNOS may be a 1,000-fold greater than that produced by endothelial NOS. Since functional iNOS gene polymorphisms have been associated with susceptibility to rheumatoid arthritis (RA), drugs blocking TNF-alpha might decrease production of cytotoxic concentrations of NO leading to beneficial effect on RA or its complications. In the present study we investigated whether the infusion of the anti-TNF-alpha-infliximab may yield a short-term effect altering circulating NO oxidation products in patients with severe RA. METHODS: We investigated 33 RA patients on periodical treatment with infliximab. Serum levels of nitrates, nitrites and NOx (nitrites+nitrates) were determined immediately prior to and after infliximab infusion. Correlation with clinical variables, laboratory markers of inflammation, metabolic syndrome features, adipokines and adhesion molecules was also assessed. RESULTS: Upon infliximab administration, serum NOx concentrations (microM) decreased significantly ([mean+/-SD: 15.0+/-8.8; median: 11.9; interquartile range: 9.2-18.5] before infliximab-time 0 (baseline) and [12.9+/-6.3; 10.9; 7.8-17.2] after infliximab infusion-time 120 minutes; p=0.03). It was also the case for nitrates (9.8+/- 8.3; 7.6; 5.5-10.2] before infliximab and [7.5+/-4.0; 6.6; 5.2-10.0] after infliximab infusion; p=0.008). There was a positive correlation between basal levels of nitrites and leptin concentration prior to infliximab administration. However, no significant correlations between NO oxidation products and clinical or other laboratory variables were found. CONCLUSIONS: Our results show, for the first time, a short-term effect of anti-TNF-alpha therapy on the levels of nitric oxide production.

Anti-TNF-alpha therapy does not modulate leptin in patients with severe rheumatoid arthritis.

OBJECTIVE: The adipocytokine leptin regulates weight centrally and participates in the regulation of the immune and inflammatory responses. Chronic systemic inflammation is of major importance in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study we investigated whether inflammation, obesity or both of these characteristics are potential determinants of circulating leptin concentrations in a group of RA patients on periodical treatment with the TNF-alpha-blocker-infliximab due to severe disease. We also assessed whether the infusion of infliximab may alter circulating leptin concentrations in patients with severe RA. METHODS: We investigated 33 patients with RA on periodical treatment with infliximab. Serum leptin levels were determined immediately prior to and after infliximab infusion. RESULTS: There was a positive correlation between body mass index of RA patients and baseline serum level of leptin (rho=0.665, p<0.001). Apart from a significant correlation with VCAM-1 (rho=0.349, p=0.04), no significant correlations between baseline leptin levels and the age at the time of the study or at the onset of the disease, disease duration, ESR and CRP levels, DAS28, lipids, insulin sensitivity, adhesion molecules, resistin, adiponectin, ghrelin or the cumulative prednisone dose at the time of the study were found. Leptin levels did not change upon infliximab infusion (p=0.48). CONCLUSION: In RA patients on TNF-alpha blocker treatment, circulating leptin levels are unrelated to disease activity but constitute a manifestation of adiposity. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by reduction in serum levels of leptin.

A diet enriched with mackerel (Scomber scombrus)-derived products improves the endothelial function in a senior population (Prevención de las Enfermedades Cardiovasculares: Estudio Santoña--PECES project).

BACKGROUND: Regular consumption of fish reduces cardiovascular risks. Here, we investigate if the consumption of products with mackerel (Scomber scombrus) with 8.82 g of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) content per 100 g of product improves parameters of endothelial function in a controlled population. MATERIALS AND METHODS: Subjects maintained a 12-week diet with products with mackerel. The population consisted of 58 senior subjects (12 withdrawals, 25 women), aged 82.08 +/- 8.13 years (Group A). Twenty-three senior subjects (13 women) on a regular diet were used as the control group (Group B). Subjects of Group A received 57 portions throughout 12 weeks (four to five portions a week of products with a mean EPA + DHA content of 2.5 g a day). A continuous follow-up and a final evaluation were performed to determine the level of consumption. Plasma samples were stored at -70 degrees C for a biochemical study. Endothelial function was analysed by reactive hyperemia with a mercury strain gauge plethysmography with measurement of blood flow in the forearm, both baseline and at the end of the 12-week diet. RESULTS: Endothelium-dependent vasodilatation significantly increased in Group A subjects (P < 0.001). No changes were found in Group B. The subgroup analyses showed that improvements were produced in Group A subjects without cardiovascular disease (P < 0.001). Nitrites/nitrates and von Willebrand factor plasma concentrations were higher in participants after the 12-week diet. CONCLUSIONS: The consumption of mackerel meat products improves endothelium-dependent, flow-mediated vasodilatation in a senior population. This finding might explain some of the cardioprotective effects of fish consumption.

High-grade inflammation, circulating adiponectin concentrations and cardiovascular risk factors in severe rheumatoid arthritis.

OBJECTIVE: To assess whether obesity and systemic inflammation are potential determinants of circulating adiponectin concentrations and whether low adiponectin levels cluster with metabolic syndrome features that are previously documented cardiovascular risk factors in rheumatoid arthritis (RA). METHODS: We investigated 33 RA patients who were treated with the TNF-alpha antagonist infliximab, immediately prior to an infliximab infusion. Adiponectin levels were also determined immediately after administration of an infliximab dose. RESULTS: Adiponectin concentrations correlated with age (R=0.465, p=0.008) and were higher in women (mean [95% confidence interval]=21,595 [15,366 to 30,349] ng/ml) than in men (9,310 [5,653 to 15,335] ng/ml)(p=0.008). C-reactive protein (CRP) levels correlated with circulating adiponectin concentrations (partial (p) R=-0.370, p=0.04), independent of age and gender. By contrast, the body mass index (BMI) did not correlate with adiponectin levels (pR=-0.039, p=0.8). Adiponectin concentrations correlated with triglycerides/HDL cholesterol ratios (pR=-0.396, p=0.03), total cholesterol/HDL cholesterol ratios (pR=-0.444, p=0.01) and high fasting plasma glucose levels (pR=-0.366, p=0.04), independent of CRP levels and the BMI. Adiponectin levels did not change (p=0.3) upon infliximab administration. CONCLUSION: In this cohort, high-grade inflammation was independently and negatively correlated with circulating adiponectin concentrations whereas low adiponectin levels clustered with metabolic syndrome features that reportedly contribute to atherogenesis in RA. Circulating adiponectin may be involved in cardiovascular disease in RA. The impact of inflammation on circulating adiponectin concentrations is not likely to be TNF-alpha mediated in RA.

Anti-TNF-alpha therapy modulates resistin in patients with rheumatoid arthritis.

OBJECTIVE: Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study, we investigated whether anti-TNF-alpha antagonist-monoclonal antibody-infliximab administration alters circulating levels of resistin, a proinflammatory adipokine. We further assessed associations of circulating resistin concentrations with CRP and ESR levels, platelet counts and metabolic syndrome and demographic characteristics in RA patients on periodical treatment with infliximab. METHODS: We investigated 33 patients with RA on periodical treatment with infliximab. Serum resistin levels were determined immediately prior to and after infliximab infusion. RESULTS: Upon infliximab administration, mean (SD) serum resistin concentrations (ng/ml) decreased from 21.9 (9.9) to 17.4 (8.9) (p=0.005). Also, a significant association between the mean ESR (r=0.405; p=0.03) and CRP (r=0.571; p=0.0005) from disease diagnosis and ESR (r=0.486; p=0.004), CRP (r=0.599; p=0.0005) and platelet count (r=0.559; p=0.0007) at the time of the study and baseline resistin levels was found. CONCLUSION: The present study shows that anti-TNF-alpha therapy results in a rapid reduction of serum resistin levels in patients with RA. It also confirms a close association between laboratory markers of inflammation, particularly CRP and resistin levels. These observations support a potential role of resistin in the inflammatory cascade in RA.

Association of the 163A/G and 1181G/C osteoprotegerin polymorphism with bone mineral density.

The aim of the study was to investigate the distribution of 163 A/G osteoprotegerin gene promoter and 1181 G/C osteoprotegerin exon 1 polymorphisms in a group of women with different hormonal status and to analyze their relationship with BMD. Osteoprotegerin polymorphisms and BMD were analyzed in 332 women (69 premenopausal and 263 postmenopausal). BMD was quantified at the lumbar spine (L 2-4), femoral neck, and total hip. Genotyping for the presence of different polymorphisms was performed using the Custom Taqman ((R)) SNP Genotyping assays. There were not significant differences in BMD according to 163 A/G genotype. However, significant differences in lumbar spine BMD were found according to 1181 G/C alleles. Thus, women with CC genotype had significant higher BMD at the lumbar spine than those with GC or GG genotype. No differences were found in femoral neck and total hip BMD. In age-adjusted models, the 1181 G/C OPG polymorphism explained 2.2% of BMD variance at the spine, 0.3% at the femoral neck, and 0.9% at the total hip in the whole group. In the subgroup of premenopausal women, the polymorphism was strongly related to spine BMD, and explained 11.5% of the variance, whereas body weight explained 7.9%. The 1181 G/C polymorphism was associated with lumbar spine BMD in Spanish women. Premenopausal women with the CC genotype had a higher BMD.

Blood-soluble Fas levels are increased in type 2 diabetic patients with peripheral vascular disease.

AIM: To investigate the possible utility of plasma sFas (soluble Fas) levels as a marker of peripheral vascular disease (PVD) in type 2 diabetic patients, and the relationship between classical cardiovascular risk factors and sFas levels in these patients. MATERIALS AND METHODS: sFas levels were measured in 57 type 2 diabetic patients with and 60 without PVD matched for age and sex. Diagnosis of PVD was established in presence of at least one of the following criteria: leg or foot amputation of vascular cause, lower-extremity arterial angioplasty or surgical by-pass, or ankle-braquial index (ABI) less than 1 in at least one side of the body. ELISA was used to measure sFas levels. RESULTS: None of the risk factors assessed total cholesterol, HDL cholesterol, triglycerides, CRP, ACE, fibrinogen, Lp(a) and homocysteine was significantly different between both groups of patients. However, patients with PVD had higher plasma sFas levels than the group without PVD (10.25+/-3.7 ng/ml VS. 8.86+/-2.6 ng/ml; p=0.02). Levels of sFas were 1.45 ng/ml (95% CI: 0.32-2.58; p=0.013) higher in PVD patients when adjusting by age, total, HDL and LDL cholesterol, triglycerides, homocysteine, CRP, ACE, arterial hypertension and tobacco smoking. Using multiple logistic regression sFas is a predictor of PVD, although not potent. CONCLUSION: Plasma sFas may be an independent marker of PVD in type 2 diabetes mellitus patients.

Influence of anti-TNF-alpha infliximab therapy on adhesion molecules associated with atherogenesis in patients with rheumatoid arthritis.

OBJECTIVE: Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). Soluble (s) adhesion molecules were found significantly increased in RA patients with active disease. Since increased levels of some adhesion molecules were closely linked to the development of endothelial dysfunction and atherosclerosis and administration of anti-TNF-alpha-infliximab resulted in a rapid and dramatic improvement of endothelial function in long-term infliximab treated RA patients, we assessed whether infusion of the chimeric anti-TNF-alpha infliximab might also yield a rapid and favorable effect on serum levels of soluble adhesion molecules in RA patients periodically treated with this drug because of severe disease. METHODS: We recruited patients with RA refractory to conventional therapy seen over a period of 2 months at Hospital Xeral-Calde, Lugo, Spain, who were on periodical treatment with infliximab for at least 14 weeks. Blood samples for determination of sICAM-1, sICAM-3, sVCAM-1, sE-selectin, and sP-selectin levels by ELISA were taken immediately before and after infliximab infusion. RESULTS: Thirty-four RA patients (25 women; mean age: 55.4 years; mean DAS28: 4.27) fulfilled the inclusion criteria. Following infliximab infusion a reduction of the overall mean values of the five adhesion molecules was observed. However, when a Wilcoxon signed-rank test was used, only significant differences for sICAM-3 and sP-selectin were observed. In this regard, sICAM-3 and sP-selectin levels fell in 26 (77%) and 28 (82%) of the 34 patients. CONCLUSION: Our study confirms a rapid and beneficial effect of infliximab infusion on expression of some adhesion molecules in RA patients treated periodically with this anti-TNF-alpha monoclonal antibody because of severe disease.

Plasma adrenomedullin levels in patients with polymyalgia rheumatica and giant cell arteritis.

OBJECTIVE: Plasma adrenomedullin (AM) levels are elevated in several inflammatory rheumatic diseases. The aims of the present study were: a) to assess whether plasma AM levels are abnormal in patients with polymyalgia rheumatica and giant cell arteritis (PMR and GCA) and b) to investigate if this parameter is related to clinical and biochemical indicators of disease activity in these patients. MATERIALS AND METHODS: AM plasma levels were analyzed in 17 patients with PMR and GCA and in 14 healthy subjects. Twelve patients (9 PMR and 3 GCA) were studied when they had active disease before any steroid therapy and the remaining 5 patients (2 PMR and 3 GCA) were in complete clinical remission and no longer receiving steroid treatment. AM was measured by a specific radioimmunoassay. RESULTS: Plasma AM concentration was significantly higher in patients with active GCA compared to the control group (p < 0.05) and with patients with isolated PMR (p < 0.05). However, there were no significant differences between patients with active PMR and the control group. Within the PMR/GCA group with active disease, AM plasma levels were positively correlated with ESR (r = 0.6, p = 0.02), and negatively with hematocrit (r = -0.57, p = 0.03) and hemoglobin (r = -0.55, p = 0.04). No correlations were found between AM and CRP. CONCLUSION: Plasma levels of AM are elevated in patients with active GCA and correlate with parameters that reflect the acute phase response. The differences in the secretion of AM between patients with PMR and GCA might reflect the severity of the vascular endothelial cell damage in these conditions. The role of AM in the pathogenesis of PMR and GCA needs to be assessed in a larger series of patients.

Levels of plasma total adrenomedullin are related with two acute phase inflammatory reactants (fibrinogen and sialic acid) but not with markers of endothelial dysfunction in Type 1 diabetes Adrenomedullin and vascular risk factors in Type 1 DM.

Adrenomedullin (AM), an ubiquitous regulatory peptide with different actions, is known to be elevated in different clinical situations, including diabetes mellitus (DM), but its potential role in the pathogenesis of diabetic vascular complications is not clear. In the present study, we examined plasma total AM levels, and their association with different markers of endothelial dysfunction and with other established risk factors for cardiovascular diseases, in patients with Type 1 DM. We studied a total of 155 patients, 117 patients without any kind of vascular complications, 24 patients with retinopathy only, and 14 patients with retinopathy and microalbuminuria but normal renal function. None of them had clinical evidence of atherosclerotic disease. Compared with the control group (64 healthy participants), patients had raised fibrinogen, soluble E-selectin ((s)E-selectin), vascular cellular adhesion molecule (VCAM), angiotensin converting enzyme (ACE), and von Willebrand factor (vWf) (P<.001 in all cases), but plasma total AM, endothelin (ET), sialic acid, and homocysteine were not raised. In the diabetic group, AM levels correlated significantly with sialic acid (r=.16; P<.05), but a more significant correlation was found with fibrinogen (r=.30; P<.001). No correlation was found with the other parameters studied. In summary, plasma total AM levels seem to correlate with inflammatory markers but not with endothelial dysfunction markers in Type 1 diabetic patients without atherosclerotic disease.

Fasting plasma ghrelin levels increase progressively after biliopancreatic diversion: one-year follow-up.

BACKGROUND: The role of ghrelin in weight control after surgery is not clear. We examined plasma ghrelin and leptin levels in patients with morbid obesity undergoing biliopancreatic diversion (BPD) of Scopinaro. METHODS: 30 adult patients (27 females, 3 males), undergoing elective BPD were recruited from the Hospital Surgery Service. Fasting blood samples for biochemical determinations were drawn before surgery and 1, 3 and 12 months after BPD. Human plasma ghrelin was measured by RIA. RESULTS: During the study period, weight, BMI and serum leptin levels decreased significantly at all sample points compared to preoperative values. Ghrelin plasma levels increased during the study, with statistical significance at 3 months and 1 year after surgery compared with preoperative levels. While leptin changes correlated with changes in BMI, no correlation was found between ghrelin and leptin or BMI changes. CONCLUSION: Plasma ghrelin levels could be decreased in obese patients as a compensatory mechanism to their nutritional state, but our results do not support the postulated beneficial role of ghrelin in the 1-year weight loss after BPD. They rather suggest that weight loss somehow stimulates ghrelin secretion, even in the absence of part of the stomach.