Circulating monoclonal immunoglobulins in Sjögren syndrome: prevalence and clinical significance in 237 patients

We conducted the current study to analyze the prevalence and clinical significance of circulating monoclonal immunoglobulins in patients with Sj?gren syndrome (SS), focusing on the association with extraglandular features, immunologic markers, hematologic neoplasia, and hepatitis C virus (HCV) infection. We performed serum immunoelectrophoresis in 200 patients with primary SS and 37 patients with HCV-related SS. All patients fulfilled 4 or more of the 1993 European classification criteria for SS.Of the 200 patients with primary SS, 35 (18%) presented circulating monoclonal immunoglobulins. The monoclonal bands identified were 20 IgG (13 kappa, 7 lambda), 10 IgM (5 kappa, 5 lambda), 2 IgAkappa, and 3 free circulating light chains. Of the 37 SS-HCV patients, 16 (43%) had circulating monoclonal immunoglobulins. The monoclonal bands identified were 10 IgMkappa, 5 IgGlambda, and 1 free light lambda chain. Compared with primary SS patients, SS-HCV patients presented a higher frequency of monoclonal immunoglobulins (43% vs 18%, p = 0.001), with monoclonal IgMkappa being the most frequent monoclonal band. Six (12%) of the 51 SS patients with circulating monoclonal immunoglobulins presented hematologic neoplasia, compared with 3 (1.6%) of those without monoclonal immunoglobulins (p = 0.004; odds ratio = 8.13; 95% confidence intervals, 1.64-51.54). In 2 of the 6 patients with monoclonal immunoglobulins and lymphoproliferative disorders, a change of the monoclonal component was detected in previous immunoelectrophoresis determinations before the development of hematologic neoplasia. Circulating monoclonal immunoglobulins were detected in nearly 20% of patients with primary SS, with monoclonal IgG being the most frequent type of immunoglobulin detected. In SS-HCV patients, the prevalence of monoclonal immunoglobulins was higher (43%), with monoclonal IgM being the most frequent type found. SS-HCV patients presented a more restrictive monoclonal expression (limited to either monoclonal IgMkappa or monoclonal IgGlambda) than primary SS patients, who showed all types of heavy and light chains.     

Influence of the degree of adherence to the mediterranean diet and its components on cardiometabolic risk during pregnancy. The GESTAFIT project

Background and aimsStudies regarding dietary patterns and cardiometabolic risk markers during pregnancy are scarce. The aim of the present study was to analyse whether different degrees of adherence to the Mediterranean diet (MD) and the MD components were associated with cardiometabolic markers and a clustered cardiometabolic risk during pregnancy.Methods and resultsThis study comprised 119 pregnant women from the GEStation and FITness (GESTAFIT) project. Dietary habits were assessed with a food frequency questionnaire at the 16th and 34th gestational weeks (g.w.). The Mediterranean Diet Score was employed to assess MD adherence. The following cardiometabolic markers were assessed: pre-pregnancy body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C). A greater MD adherence was associated with a better cardiometabolic status in cross-sectional (16th g.w. and 34th g.w.) and prospective analyses (MD adherence at the 16th g.w. and cardiometabolic markers at the 34th g.w.; SBP, DBP and HDL-C; all, p < 0.05). Participants with the highest MD adherence (Tertile 3) had a lower clustered cardiometabolic risk than those with the lowest MD adherence (Tertile 1) at the 16th and 34th g.w. (both, p < 0.05). A higher intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts were associated with a lower cardiometabolic risk during pregnancy (all, p < 0.05).ConclusionA higher MD adherence, a greater intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts showed a cardioprotective effect throughout gestation.     

Preventive effect of zaprinast and 3-isobutyl, 1-methylxanthine (phosphodiesterase inhibitors) on gastric injury induced by nonsteroidal antiinflammatory drugs in rats

Cyclic GMP plays an important role in maintaining homeostasis in the gastric mucosa. NSAIDs damage the mucosa by mechanisms that may be mediated by alterations in the intragastric concentration of cyclic GMP. To test this hypothesis we studied the effects of the oral administration of acetylsalicylic acid (100, 300, and 500 mg/kg), piroxicam (5, 10, and 20 mg/kg) and sodium diclofenac (10, 25, 50, and 100 mg/kg), and of their interaction with zaprinast (5 mg/kg) and IBMX (10 mg/kg), on intragastric concentrations of cyclic GMP and the gastric erosive index in rats. All determinations were done 3 hr after the NSAID was given. All NSAIDs induced dose-dependent decreases in mucosal concentrations of cyclic GMP, which correlated inversely with the surface area showing mucosal injury. In contrast, cyclic GMP concentrations remained normal, and no intragastric damage was seen in rats given zaprinast (cyclic GMP-specific phosphodiesterase inhibitor) or IBMX (non-specific phosphodiesterase inhibitor) or in combination with NSAIDs. These findings are in line with the hypothesis that cyclic GMP is involved in the biochemical mechanisms of NSAID-induced gastric injury.     

MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells

MT1-MMP plays a key role in endothelial function, as underscored by the angiogenic defects found in MT1-MMP deficient mice. We have studied the molecular interactions that underlie the functional regulation of MT1-MMP. At lateral endothelial cell junctions, MT1-MMP colocalizes with tetraspanin CD151 (Tspan 24) and its associated partner alpha3beta1 integrin. Biochemical and FRET analyses show that MT1-MMP, through its hemopexin domain, associates tightly with CD151, thus forming alpha3beta1 integrin/CD151/MT1-MMP ternary complexes. siRNA knockdown of HUVEC CD151 expression enhanced MT1-MMP-mediated activation of MMP2, and the same activation was seen in ex vivo lung endothelial cells isolated from CD151-deficient mice. However, analysis of collagen degradation in these experimental models revealed a diminished MT1-MMP enzymatic activity in confined areas around the cell periphery. CD151 knockdown affected both MT1-MMP subcellular localization and its inclusion into detergent-resistant membrane domains, and prevented biochemical association of the metalloproteinase with the integrin alpha3beta1. These data provide evidence for a novel regulatory role of tetraspanin microdomains on the collagenolytic activity of MT1-MMP and indicate that CD151 is a key regulator of MT1-MMP in endothelial homeostasis.     

HIV-associated lymphoma successfully treated with peripheral blood stem cell transplantation

OBJECTIVE: To evaluate feasibility, safety, and efficacy of peripheral blood stem cell collection (PBSCC) and autologous stem cell transplantation (ASCT), to treat patients diagnosed of high-risk or relapsed HIV-associated lymphoma (HIV+ Ly), responding to highly active antiretroviral therapy (HAART). METHODS: Prospective and multicentric study in patients with high-risk or relapsed chemosensitive HIV+ Ly, candidate for consolidation with ASCT. Eligibility criteria were similar to those of HIV- lymphoma. HAART was aimed to be maintained during the procedure. RESULTS: Fourteen patients were admitted. Adequate PBSCC was obtained from all patients (median CD34+ cells was 4.7 x 10(6)/kg). Three patients died before ASCT; two had disease progression and one died from VHC-liver failure. Eleven transplanted patients showed neutrophil engraftment after a median time of 16 days (range, 9-33 days), and nine patients showed platelet engraftment after a median time of 20 days (range, 11-36 days). CD4+ cell counts and HIV viral load (VL) were appropriately preserved along the procedure. No patients died from treatment-related complications. One patient died from lymphoma progression (day +19), and another died in complete remission (CR) with undetectable VL, 15 months after transplant, due to infection. One patient relapsed at 32 months after ASCT. The remaining eight patients are alive in CR with an event-free survival of 65% and a median follow-up of 30 months after ASCT (range, 7-36 months). CONCLUSIONS: These results show that feasibility, safety, and efficacy of PBSCC and ASCT in HIV+ Ly patients responding to HAART are similar to those observed in the HIV- lymphoma setting.     

Ghrelin: beyond hunger regulation

Man ingests food to mitigate hunger (mediated by physiological and biochemical signals), satisfy appetite (subjective sensation) and because of psychosocial reasons. Satiation biomarkers (stop feeding) are gastric distention and hormones (CCK, GLP-1) and satiety biomarkers (induce feeding) are food-induced thermogenesis, body temperature, glycaemia and also hormones (insulin, leptin and ghrelin). Oxidative metabolism/body composition, tryptophan/serotonin and proinflammatory cytokines are also implicated on hunger physiology. At the present time, ghrelin is the only known circulating orexigenic with potential on hunger/body weight regulation. It is a neuropeptide (endogenous ligand for the GH secretagogue) recently isolated from the oxyntic mucosa and synthesized mainly in the stomach. Its blood concentration depends on diet, hyperglucemia and adiposity/leptin. It is secreted 1-2 hours preprandially and its concentration decreases drastically during the postprandium. Ghrelin acts on the lateral hypothalamus and theoretically inhibits proinflammatory cytokine secretion and antagonizes leptin. Ghrelin physiologically increases food intake and stimulates adipogenesis, gastrointestinal motility and gastric acid secretion, and has other hormonal and cardiovascular functions. Ghrelin blood concentration is reduced in massive obesity, non-alcoholic steatohepatitis, polycystic ovary syndrome, acromegaly, hypogonadism, ageing, short bowel syndrome and rheumatoid arthritis; and increased in primary or secondary anorexia, starvation, chronic liver disease and celiac disease. Cerebral and peritoneal ghrelin administration (rats) and systemic administration (rats and healthy volunteers, cancer patients or patients on peritoneal dialysis) promotes food consumption and increases adiposity, of utmost importance in the treatment of patients with anorexia.     

Cardiac damage in hypertensive patients with inverse white coat hypertension. Hospitalet study

BACKGROUND: Few studies have assessed the relationship between ambulatory blood pressure (BP) and cardiac damage in essential hypertensive patients with inverse white coat hypertension (IWCH). OBJECTIVES: To determine the frequency of IWCH in untreated grade 1-2 hypertension and to assess possible differences in cardiac damage among patients with IWCH, white coat hypertension (WCH) and the rest of patients with grade 1-2 hypertension. PATIENTS AND METHODS: Two hundred and eleven patients with grade 1-2 hypertension were sequentially included. A good quality 24-h ambulatory BP monitoring was obtained in 204 patients (age: 41 +/- 12 years, 56% males). IWCH was defined as a daytime systolic and/or diastolic BP higher than diagnostic office systolic and/or diastolic BP, respectively. WCH was defined as a daytime BP < 135/85 mmHg. A good quality echocardiogram was obtained in 174 patients. We considered left ventricular hypertrophy a left ventricular mass index (LVMI) > or = 125 g/m2. RESULTS: We found IWCH in 29 subjects (14%), and WCH in 68 (33%). Office BP in patients with IWCH was in an intermediate position between WCH and the rest of grade 1-2 hypertension patients. The IWCH patients showed 24-h, daytime and night-time BP higher than the other groups. Left ventricular mass was significantly greater in patients with IWCH than in the other grade 1-2 hypertension patients after adjusting for age, gender, body mass index, smoking and office BP (regression coefficient 28.14, 95%CI: 7.36-48.91). CONCLUSION: IWCH is independently associated with higher values of left ventricular mass in patients with grade 1-2 hypertension.     

Prothrombin A19911G and G20210A polymorphisms' role in thrombosis

The prothrombin G20210A polymorphism, which correlates with the plasmatic prothombin levels, is the second genetic risk factor for deep venous thrombosis (DVT), although its prothrombotic role is mild. Recently, the prothrombin A19911G polymorphism, also associated with slight variations of the prothrombin level, has been suggested to modulate the thrombotic risk of the G20210A polymorphism in a preliminary study including few patients and controls. Our study evaluated the effect of the A19911G polymorphism in the arterial and venous thrombotic risk of the prothrombin 20210G/A genotype, analysing 204 consecutive DVT patients and 204 matched controls. Moreover, we analysed 213 carriers of the 20210G/A genotype (152 with DVT, 26 with arterial thrombosis and 35 healthy subjects) and 10 homozygous 20210 A/A carriers. We developed a simple method to simultaneously determine the genotype of both polymorphisms. In accordance with our case/control study, the A19911G polymorphism did not play a significant role in the development of DVT. Analysis of 120 20210 A alleles demonstrated a complete linkage disequilibrium with the 19911 A allele. These polymorphisms (alone or combined) did not modify the risk of arterial thrombosis. However, the 19911A/G genotype slightly increased the risk of developing DVT in carriers of the 20210G/A genotype (OR 3.34 vs 5.86), supporting that the prothrombin 19911 polymorphism could modulate the risk of the G20210A polymorphism in developing DVT.     

First Report of Paralytic Shellfish Toxins in Marine Invertebrates and Fish in Spain

A paralytic shellfish poisoning (PSP) episode developed in summer 2018 in the Rías Baixas (Galicia, NW Spain). The outbreak was associated with an unprecedentedly intense and long-lasting harmful algal bloom (HAB) (~one month) caused by the dinoflagellate Alexandrium minutum. Paralytic shellfish toxins (PSTs) were analyzed in extracts of 45 A. minutum strains isolated from the bloom by high-performance liquid chromatography with post-column oxidation and fluorescence detection (HPLC-PCOX-FLD). PSTs were also evaluated in tissues from marine fauna (invertebrates and fish) collected during the episode and in dolphin samples. The analysis of 45 A. minutum strains revealed a toxic profile including GTX1, GTX2, GTX3 and GTX4 toxins. With regard to the marine fauna samples, the highest PSTs levels were quantified in bivalve mollusks, but the toxins were also found in mullets, mackerels, starfish, squids and ascidians. This study reveals the potential accumulation of PSTs in marine invertebrates other than shellfish that could act as vectors in the trophic chain or pose a risk for human consumption. To our knowledge, this is the first time that PSTs are reported in ascidians and starfish from Spain. Moreover, it is the first time that evidence of PSTs in squids is described in Europe.