Metabolic syndrome: its features in overweight women with polycystic ovary syndrome as compared with obese women without ovarian dysfunction?

UNLABELLED: OVARIAN DYSFUNCTIOBJECTIVE: The study assesses the frequency of metabolic changes in overweight patients with or without polycystic ovary syndrome. MATERIAL AND METHODS: The study group was made up by 148 patients of whom 99 patients without polycystic ovary syndrome (group A, control group) and 49 with polycystic ovary syndrome (group B), that came in our endocrine unit for a weight loss program, in the September 2008 March 2009 period. Morphometric parameters (height, weight, body mass index), biological parameters (cholesterol, triglycerides, blood glucose, glycated hemoglobin) and body composition analysis by measuring the electrical bioimpedance, were evaluated. RESULTS: Patients with polycystic ovary syndrome have a higher percentage of total fat (38.22+/-7.2) than patients without polycystic ovary syndrome (36.316+/-5.65) (p<0.05), for the same characteristics. Glycated hemoglobin, blood glucose and triglycerides were found higher in group B patients. Furthermore, the amount of free testosterone is higher in group B patients compared to those in group A. The prevalence of metabolic syndrome was higher in polycystic ovary syndrome cases (26.13%) comparative with overweight cases (16.16%, p<0.01). CONCLUSIONS: In the group of overweight patients, the group of patients with polycystic ovary syndrome is a particular group showing more severe metabolic changes.

Diagnostic value of a negative single color duplex ultrasound in deep vein thrombosis suspicion during pregnancy.

OBJECTIVE: to determine whether a negative single complete ultrasound (US) of the lower limbs veins is a safe and accurate diagnostic method to rule out deep venous thrombosis (DVT) in pregnancy. MATERIAL AND METHODS: We performed a prospective study on 87 consecutive pregnant women with clinical suspicion of DVT in "Dr. D. Popescu" Maternity, Timisoara, between January 2007 and December 2009. All cases were investigated by color duplex ultrasound. Those who were negative but with high clinical probability of DVT underwent MR venography, the rest with negative US findings did not received anticoagulant therapy and US was repeated after seven days. All were instructed about the signs and symptoms of DVT and asked to return at six weeks postpartum when they were questioned if presented any. RESULTS: from the 87 women 30 (34.48%) were found positive and two (2.29%) had a high clinical suspicion of DVT. 55 (63.21%) with negative findings repeated the US exam after 7 days which remained negative. Only 43 (78.18%) returned for the 6 weeks postpartum visit and none of them experienced any thromboembolic event during follow-up. CONCLUSIONS: A single complete color duplex ultrasonography of lower limbs veins appears to be a safe method to rule out the diagnosis of deep venous thrombosis in pregnant women and if negative is safe to withhold heparin therapy.

The T-cell suppressive effect of bufadienolides: structural requirements for their immunoregulatory activity.

Many studies indicate that substances similar to cardenolides and bufadienolides naturally occur in mammals. The majority of previous studies focused on their cardiovascular, renal, and central nervous action. We analyzed the immunoregulatory property of 52 bufadienolides. Human T-cells were stimulated "in vitro" with mitogens or alloantigens in the presence of bufadienolides. The most active compound totally inhibited T-cell activity at a concentration of 0.75 pmol/10(5) cells. This effect is 16,384 x stronger than that of cortisol and 256 x stronger than that of cyclosporin A or tacrolimus. Preactivated T cells were downregulated and, most importantly, suppressed viable T cells could not be restimulated. Lack of the 17 beta-lactone ring dramatically reduced the activity of bufadienolides. Substitution at C3 also affected their function: components with a 3-OH group were up to 1000 x stronger than those without. The replacement of 14 beta-OH with an epoxy-group slightly decreased the activity. Because there is evidence that the latter change abolishes the cardiac activity, this finding is relevant for therapeutic applications in which immunosuppression without the risk of cardiotoxicity is attempted. One of the substances analyzed in this study was Proscillaridin A. A similar bufadienolide occurs naturally in mammals. We speculate that bufadienolides represent an important bioregulatory link between the cardiovascular, nervous and immune systems.

Inverse association between IgG-anti-kappa and antierythrocyte autoantibodies in patients with cold agglutination.

It has been known for a long time that IgG-anti-F(ab')(2) antibodies (Abs) are able to suppress the B-cell response. We showed that natural IgG-anti-F(ab')(2) autoantibodies appear in the serum of patients with cold agglutination. If the anti-F(ab')2 Ab suppresses cold agglutinin (CA)-producing B cells, one would expect an inverse correlation between the titers of these two Abs. Our study confirmed this correlation. Subsequent experiments showed that some anti-F(ab')(2) Abs bind to the hinge region of IgG. It was difficult to explain how this Ab suppresses CA-producing B cells, which are of IgM isotype. Here we show that patients with cold agglutination have an IgG-anti-kappa light chain autoantibody in their serum. This is another member of the anti-F(ab')(2) Ab group. Because the vast majority of CAs are IgM-kappa Abs, the anti-kappa Ab might suppress CA-producing B cells. If this is the case, there should be an inverse association between the titer of anti-kappa Ab and CA. In a group of 302 patients, we found that high titers of the anti-kappa Ab correlate with low titers of CA and vice versa (P =.009). Interestingly, this association is found only in patients whose disease is caused by noninfectious agents, including mainly B-cell proliferations (P =.0058). Our data show that the inverse correlation is not confined to a particular CA autoantibody specificity. The results are discussed in the light of recent findings showing that anti-IgM Abs may either inactivate or kill tumoral B cells by apoptosis.

Inverse correlation between IgG-antihinge region and antierythrocyte autoantibody in chronic benign and malignant cold agglutination.

Previous reports provided evidence of an immunosuppressive role of natural anti-F(ab')2 antibodies. If suppressive anti-F(ab')2 antibodies also regulated the autoantibody production in cold agglutination, one would expect high titers of anti-F(ab')2 to be associated with low titers of cold agglutinins. Indeed, our previous studies revealed an inverse correlation between IgG-anti-F(ab')2 and cold agglutinins. Many previous experiments focused on anti-F(ab')2 of an antiidiotypic nature. Recent epitope mapping showed that anti-F(ab')2 of healthy persons is not an antiidiotype but recognizes a hinge region sequence. We attempted to answer the question whether this IgG-antihinge antibody is responsible for the previously described association between anti-F(ab')2 and cold agglutinins. IgG-antihinge and IgG-anti-F(ab')2 antibody was determined and statistically analyzed in the serum of 334 patients with cold agglutination. Our experiments revealed a strong correlation between the concentrations of antihinge and the previously described anti-F(ab')2 antibody. The anti-F(ab')2 activity was competitively inhibited by a synthetic hinge peptide. Moreover, patients with high antihinge titers had low cold agglutinin titers, and vice versa. A stratification according to cold agglutinin specificity and disease etiology showed that the inverse correlation is present only in anti-I and anti-i patients suffering from monoclonal B-lymphocyte proliferation. In conclusion, our results confirm the correlation previously described for anti-F(ab')2 antibody and antierythrocyte autoantibody and define for the first time an association between an idiotype-independent anti-IgG autoantibody and cold agglutinin.

A natural IgA-anti-F(ab')2gamma autoantibody occurring in healthy individuals and kidney graft recipients recognizes an IgG1 hinge region epitope.

Natural anti-IgG autoantibodies are found both in healthy individuals and in patients with certain diseases. One group of these Abs recognizes epitopes located in the F(ab')2 region of the IgG molecule. The immunoregulatory role of these Abs in healthy individuals, graft rejection, and disease was previously studied, usually with a focus on the characterization of anti-idiotypic Abs. In the present study, we characterize the epitope recognized by an anti-F(ab')2gamma autoantibody of the IgA isotype, which occurs in the serum of healthy individuals and kidney transplant recipients. The autoantibody described herein reacts strongly with F(ab')2gamma but only poorly with Fab(gamma) fragments, a binding pattern pointing to an epitope located in the hinge region. Using synthetic peptides, we identified a conformational epitope that overlaps the middle and part of the lower hinge region. Structural analyses of peptide constructs showed that a defined conformation of the first three residues of the lower hinge is required for a full expression of the epitope. Binding of IgA to the hinge region of IgG1 covers part of the physiologically active Fc domain, immobilizes the Fab arms, and thereby can be expected to exert immunoregulatory functions.

Striking inverse correlation between IgG anti-F(ab')2 and autoantibody production in patients with cold agglutination.

Previous experiments showed that the physiologic IgG anti-F(ab')2 antibody suppresses the response of human autoreactive B cells. In the present study, we analyzed the IgG anti-F(ab')2 antibody in 293 patients with cold agglutination (CA). Their average IgG anti-F(ab')2 titer was not much different (211 +/- 8.3) from that of 279 healthy persons (195 +/- 6.7). However, CA patients with high anti-F(ab')2 titers had low CA autoantibody titers and vice versa (P = .0028; rho = -0.175). The stratification of patients according to the auto-antibody's specificity (anti-I, anti-i, anti-Pr) showed an inverse correlation between anti-F(ab')2 and CA in the anti-I group (P = .0057; rho = -0.180). Interestingly, the association was present only in patients whose disease was caused by noninfectious agents (P < .0001; rho = -0.423). The inverse correlation argues for an important role of the IgG anti-F(ab')2 in the regulation of autoantibody production in CA patients.