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Biomedical subjects

S Pierangeli

Publications and source records attributed to S Pierangeli.

At least 19 recordsLinked to original sources

Amenorrhea after weight recover in anorexia nervosa: role of body composition and endocrine abnormalities.

UNLABELLED: Hypothalamic amenorrhea in anorexia nervosa often precedes weight loss and may persist after re-feeding and restoration of a stable normal weight. AIM: To assess the rate of persistent amenorrhea in anorexia nervosa (AN) after re-feeding and the relations of this condition with body composition changes and other endocrine parameters. METHODS: A cohort of 250 female outpatients was studied to assess persistent amenorrhea prevalence after stable weight recovery. Among these, we selected 20 AN female patients (age 16.5-35), 10 with amenorrhea (group 1) and 10 with normal menses (group 2). We collected data such as age, age at menarche, age at onset of AN, actual body mass index (BMI) and at onset of AN, duration of disease. Physical activity has been evaluated as minute per day. The following data were obtained: prolactin, growth hormone, estradiol, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone, free triiodothyronine, free thyroxine, free urinary cortisol, serum calcium and phosphates, urinary calcium, phosphaturia and alkaline phosphatase. Body composition was assessed with a dual energy x-ray absorptiometry (DEXA). RESULTS: Thirty-five patients (14%) over a cohort of 250 where still amenorrhoic after stable weight recovery. No significance was found in the evaluation of blood biochemical tests of the 2 groups. Free urinary cortisol was significantly higher in amenorrhoic patients (58.14+/-0.4 vs 15.91+/-9.5), p=0.02. The analysis of body composition has shown a percentage of fat of 22.23+/-5.32% in group 1 and of 26.03%+/-9.1% in group 2, respectively, showing no significant differences. Amenorrhoic patients carried on doing a significantly heavier physical activity than eumenorrhoic patients. CONCLUSIONS: An adequate body composition and a well represented fat mass are certainly a necessary but not sufficient condition for the return of the menstrual cycle. Such menstrual cycle recovery would probably need other conditions at present being studied and evaluated to occur, such as secretory patterns of leptin and its correlations with adrenal function.

Adolescent↗

The molecular basis of antiphospholipid syndrome.

We herein review evidence that the phospholipid-binding protein beta2 glycoprotein-1 (beta2GPI) is a causative autoantigen in APS. Recent work suggests that the molecular regions in beta2GPI that facilitate autoimmunization are those that promote binding to negatively charged phospholipids by means of strong positive (anionic) charge and hydrophobicity. Although many common infections can cause antiphospholipid antibodies to be produced in humans, such postinfectious aPL are rarely associated with thromboses or pregnancy morbidity, the central features of antiphospholipid syndrome (APS). We propose that the causes of APS include those infectious agents that mimic the above molecular domains in beta2GPI. In people who are susceptible to APS, tolerance to self-beta2GPI and phospholipids is likely to be broken by foreign bacterial or viral proteins that contain such beta2GPI-like epitopes.

Animals↗

Osteoporosis and anorexia nervosa: relative role of endocrine alterations and malnutrition.

BACKGROUND AND AIM: Anorexia nervosa (AN) is a psychiatric disorder characterised by self-induced starvation or a very reduced caloric intake, and frequently by severe life-threatening protein calory malnutrition. Its physiological consequences include amenorrhea, estrogen deficiency and osteoporosis. Osteoporosis may develop as a consequence of a lack of estrogens, low calcium or vitamin D intake, hypercortisolemia or the duration of the illness. The aim of this study was to identify the best endocrinological and nutritional indicators of bone density. SUBJECTS AND METHODS: The study involved 49 young females with AN and malnutrition and 24 age-matched normal controls in whom AN had been excluded on the basis of a clinical evaluation using DSM IV criteria. We studied bone density in early osteopenia, a condition in which the potential risk of fractures is certainly high and traditionally related to a variety of endocrinological and nutritional factors. RESULTS: Bone density was significantly lower in the AN than the control group in all of the examined bone districts: bone mineral density (BMD) spine 0.89 +/- 0.19 vs 1.27 +/- 0.2 (p<0.0001), BMD neck 0.75 +/- 0.14 vs 1.08 +/- 0.17 (p<0.001), BMD Ward 0.74 +/- 0.17 vs 1.12 +/- 0.11 (p<0.0001). Non-significant differences were found in the patients who had undergone previous estrogen medication. Body mass index (BMI) correlated with bone density, but caloric and calcium intake were not significant predictors. IGF-1, a known nutritionally dependent trophic bone factor, was significantly reduced in our patients but did not correlate with BMD. Like other authors, we found a close correlation between lean body mass and BMD in neck and spine. Physical exercise, urinary free cortisol osteocalcin and type I collagen-telopeptide (NTX) did not significantly correlate with the degree of osteopenia. CONCLUSIONS: Our data suggest the importance of nutritional factors (particularly lean body mass and BMI) in determining bone mass, and the relatively limited importance of endocrinological factors with the exception of the duration of amenorrhea as an indirect indicator of endocrinological status.

Adult↗

Pregnancy complicated by the antiphospholipid syndrome: outcomes with intravenous immunoglobulin therapy.

OBJECTIVE: To assess maternal and fetal outcomes in 15 patients with antiphospholipid syndrome (19 pregnancies) treated with intravenous immunoglobulin (IV Ig) during pregnancy. METHODS: Monthly IV Ig therapy was initiated in the first or early second trimester of all pregnancies except two. Additional therapy consisted of low-dose aspirin and subcutaneous heparin. Six patients also received steroid therapy. Serial anticardiolipin IgG levels were measured in eight pregnancies. RESULTS: The live-birth rate was 84% (16 of 19 live births), and there were three pregnancy losses. There were no cases of fetal growth restriction (FGR). Preeclampsia and nonreassuring fetal status were each diagnosed in 25% of the pregnancies. Seventy-five percent of the infants were delivered at 34 weeks' gestation or later. Anticardiolipin IgG decreased throughout the course of therapy in seven pregnancies. Placental pathology was minimal. CONCLUSION: Pregnancy complications appear to be minimized with the use of IV Ig. Definitive recommendations regarding the use of IV Ig in pregnancy await the conclusion of randomized trials. If the combination of IV Ig, aspirin, and heparin significantly decreases the incidences of FGR and prematurity, it may be a cost-effective primary therapy for pregnancies complicated by the antiphospholipid syndrome.

Adult↗

The effect of severe burn injury on proinflammatory cytokines and leukocyte behavior: its modulation with granulocyte colony-stimulating factor.

Severe injury causes immunosuppression. The main contributors are impaired leukocyte function and a cytokine dysbalance. GCSF increases PMN count, function and modulates the inflammatory response. However GCSF may overactivate leukocytes. The purpose of this study is to investigate whether GCSF is able to restore immune competence after severe injury. Lewis rats were divided into three groups: 30% TBSA burn + vehicle; 30% TBSA burn + GCSF (150 microg rhGCSF); Control. Blood samples were taken for total white cell count, PMNs, TNFalpha and IFNgamma. Leukocyte rolling and sticking were measured in the cremaster muscle microcirculation. Leukocyte diapedesis was investigated by lavage of the abdominal cavity and the lungs. Total white cell and PMN counts in the burn + GCSF group were significantly higher (P<0.001) than in burn+vehicle animals. Leukocyte adherence and diapedesis were not elevated in the burn + GCSF group as compared to the burn + vehicle group. TNFalpha (P<0.05) and IFNgamma (P<0.001) levels were significantly increased in the burn + vehicle animals compared to the burn + GCSF animals. GCSF modifies the immune system, as shown by an increase in white cell and PMN counts and by balancing the overall immune response from proinflammatory to normal, as shown by decreased TNFalpha and IFNgamma levels. GCSF does not overactivate PMNs.

Abdomen↗

Lipid interactions with human antiphospholipid antibody, beta 2-glycoprotein 1, and normal human IgG using the fluorescent probes NBD-PE and DPH.

Recurrent venous thrombosis, arterial thrombosis and pregnancy losses are clinical manifestation associated with antiphospholipid antibody (aPL) that recognizes negatively charged phospholipid antigens. Enzyme-linked immunosorbent assays (ELISA) are generally used to determine the presence and specificity of aPL. In this paper, a fluorescence spectroscopy method has been applied, through monitoring the alteration of fluorescence intensity and anisotropy of a fluorophore that was incorporated in liposomes to explore the changes of molecular structure or configuration elicited by the binding aPL with phospholipid antigens. The bilayer surface was markedly ordered by aPL binding as indicated by the surface-sensitive probe NBD-PE. The binding of aPL on the bilayer surface is saturable. The saturation concentration of aPL is 40% (w/w, aPL/lipid) for cardiolipin membranes. The binding of aPL on cardiolipin took place in the absence of beta 2-GP1. The addition of beta 2-GP1 further increased the anisotropy and decreased the intensity of fluorescence. The binding of aPL is predominantly attributed to electrostatic interaction, but the configuration of the acyl chains of phospholipid also plays a role. It is found that the thermal history is important for aPL binding. The incubation at 37 degrees C is more favorable for aPL binding than ambient temperature. Normal human serine (IgG-NHS) did not elicit any distinct change of NBD-PE fluorescence, which indicates it does not interact with the lipid.

Animals↗

Do leukocytes contribute to impaired microvascular tissue perfusion after arterial repair?

Impaired capillary perfusion may result in flap failure. Platelet emboli, polymorphonuclear leukocytes (PMNs), and/or vasospasm have been identified as possible causes. This study investigates the role of PMNs in causing impaired capillary perfusion in a free flap model. PMN concentrations were depleted using antineutrophil serum. The cremaster muscles of 20 Sprague-Dawley rats were isolated on a single neurovascular pedicle and after a simulated technically poor arterial anastomosis upstream and reperfusion, capillary perfusion was measured each hour for 6 hours. Even though the number of PMNs was significantly reduced in the animals treated with antineutrophil serum, capillary perfusion was not changed compared with controls. These results demonstrate that depleting circulating PMNs does not protect capillary perfusion in our model. These findings suggest that reduced capillary perfusion downstream from an anastomotic repair is not mediated by the presence of PMNs in the microcirculation.

Anastomosis, Surgical↗

Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice.

BACKGROUND: Previous studies have demonstrated that human monoclonal and polyclonal anticardiolipin antibodies have thrombogenic properties in vivo. Using such a model in which these antibodies have been shown to increase both the size of an induced thrombus and the duration of time in which such a clot lasts, we investigated whether hydroxychloroquine alters the dynamics of such thrombus formation. METHODS AND RESULTS: Three groups of nine mice were injected with purified immunoglobulin G (IgG) from a patient with the antiphospholipid syndrome (IgG-APS) and then fed with hydroxychloroquine at various doses (100, 6, and 3 mg/kg body wt). Three control groups of mice were also studied, including mice injected with IgG-APS and then fed with placebo, as well as two other groups injected with IgG from normal human serum and fed either hydroxychloroquine or placebo. A standardized thrombogenic injury was subsequently induced in the femoral vein of each mouse and the area (size) of thrombus measured as well as the total period of time that thrombus was present. Mice treated with hydroxychloroquine and IgG-APS showed significantly smaller thrombi that persisted for a shorter period of time compared with animals treated with IgG-APS and placebo. CONCLUSIONS: Hydroxychloroquine significantly diminished both thrombus size and total time of thrombus formation in mice previously injected with IgG-APS.

Animals↗

Antiphospholipid antibodies and cerebral lupus.

Antiphospholipid antibodies probably play a minor role in cerebral lupus. They are associated primarily with stroke and transient ischemic attacks, which occur only in a minority of patients with central nervous system complications of SLE. However, ready demonstration of functional effects of antiphospholipid antibodies in the coagulation system as well as persuasive evidence that they can induce thrombosis and pregnancy loss in experimental mice lend credence to the belief that many autoantibodies play a direct role in disease pathogenesis. Hence the role of the many autoantibodies associated with CNS lupus is a legitimate field of inquiry. This review outlines the history of antiphospholipid antibodies, discusses the controversy concerning antiphospholipid antibody specificity, summarizes recent experimental data on their functional effects in the coagulation system, and describes animal models of the antiphospholipid syndrome in which antibodies with cardiolipin-binding activity have been shown to play a direct role in thrombosis and pregnancy loss.

Animals↗

Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome.

OBJECTIVE: To determine whether antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin are associated with recurrent pregnancy loss. METHODS: Sera from three groups of women were studied: 1) 147 women with recurrent pregnancy loss but no clinical signs or symptoms of autoimmune disease who tested negative for lupus anticoagulant and medium-to-high levels of immunoglobulin G anticardiolipin antibodies; 2) 104 healthy, fertile controls of similar age and gravidity; and 3) 43 women with well-characterized antiphospholipid syndrome. Serum antibody binding against six phospholipids (cardiolipin, phosphatidic acid, phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol) was determined using enzyme-linked immunoassays, and results were normalized using an anticardiolipin standard. RESULTS: Twenty-six (18%) women with recurrent pregnancy loss and nine (9%) controls tested positive (above the 99th percentile) for antiphospholipid antibodies. Sera from five (3.4%) women with recurrent pregnancy loss and four (3.8%) controls demonstrated binding to phospholipid antigens other than cardiolipin. In contrast, binding to phospholipid antigens was demonstrated in sera from more than 90% of women with antiphospholipid syndrome. Among women testing positive for antiphospholipid antibodies, the median positive value for women in the antiphospholipid syndrome group was significantly higher than for those with recurrent pregnancy loss or normal fertile controls. CONCLUSIONS: Women with recurrent pregnancy loss are no more likely than fertile controls to have elevated levels of antiphospholipid antibodies once lupus anticoagulant, anticardiolipin, and an obvious clinical history of autoimmune disease have been excluded. Testing for antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin is not clinically useful in the evaluation of recurrent pregnancy loss.

Abortion, Habitual↗

In vitro platelet aggregation studies in microvascular surgery research: a method in the rat model.

There is now a growing awareness of the central role of platelet function in microvascular thrombosis. Platelet aggregation studies remain one of the most useful ways of studying platelet function and response to different stimuli. This brief communication highlights some of the main variables that can affect platelet aggregation in rats and emphasizes the existence of important differences in these variables compared with human platelet aggregation.

Anastomosis, Surgical↗

Diastolic dysfunction is a feature of the antiphospholipid syndrome.

Recurrent thrombi, thrombocytopenia, pregnancy loss, and stroke in association with medium to high concentrations of anticardiolipin antibodies are well-recognized features of antiphospholipid syndrome. Cardiac manifestations of primary antiphospholipid syndrome (PAPS) also have been documented but involve structural and valvular heart disease. Diastolic dysfunction in PAPS has not been well described. Therefore, 10 patients with PAPS (nine women and one man) of mean age 30 +/- 7 years (range 20 to 46 years) and 10 healthy age-, sex-, weight-, and height-matched control subjects were studied by echocardiography. Anticardiolipin antibody concentrations of patients with PAPS were > 80 immunoglobulin G phospholipid units as determined by enzyme-linked immunosorbent assay. Doppler-derived parameters of left ventricular filling showed a significant association between PAPS and diastolic dysfunction compared with control, as evidenced by a decrease in peak early filling velocity (52 +/- 10 cm/sec vs 67 +/- 12 cm/sec; p < 0.01), a decrease in the ratio of peak early to peak atrial filling velocities (1.03 +/- 0.40 vs 1.52 +/- 0.28; p < 0.005), a decrease in the mean deceleration rate of early filling (338 +/- 75 cm/sec2 vs 590 +/- 227 cm/sec2; p < 0.005), and an increase in the percentage of atrial contribution to filling and deceleration time. Left ventricular mass, diastolic filling time, and heart rate did not differ between groups. Left ventricular systolic function was normal and ejection fraction did not differ between patients with PAPS and control subjects (63% +/- 2% vs 65% +/- 7%; p not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Anticardiolipin wet workshop report. Fifth International Symposium on antiphospholipid antibodies.

An anticardiolipin wet workshop was conducted at the Fifth International Antiphospholipid Symposium (San Antonio, Texas, September 9-12, 1992). The workshop had four objectives: 1. to determine variability in measurement of immunoglobulin (Ig) G, IgM, and IgA anticardiolipin of eight unknown sera; 2. to examine the correlation between three commercial enzyme-linked immunosorbent assay (ELISA) kits and the Antiphospholipid Standardization Laboratory; 3. to examine protocols by which anticardiolipin binding to phospholipid antigens and beta 2 glycoprotein 1 (beta 2GP1) might be compared; and 4. to examine the beta 2GP1 effect on cardiolipin binding activity. Results showed good overall correlation of quantitative anticardiolipin measurements between workshop participants and the Antiphospholipid Standardization Laboratory. Correlation with individual ELISA kits was also good. With respect to the third objective, all participants showed comparable binding to cardiolipin and phosphatidylserine but none to phosphatidylcholine or beta 2GP1. Finally, beta 2GP1 enhanced, but was not essential for, anticardiolipin binding. This workshop will not settle controversies about anticardiolipin measurement and specificity, but suggests protocols to resolve these issues.

Antibodies, Anticardiolipin↗

Anticardiolipin antibodies: specificity and function.

Antibodies detected by solid phase anticardiolipin immunoassays are heterogeneous but understanding the nature of this heterogeneity has proven difficult. Differences in any of the following features may account for differences in anticardiolipin antibodies: avidity for cardiolipin, phospholipid cross-reactivity, specificity for beta 2 glycoprotein I (beta 2GPI)-cardiolipin complexes, functional activity (as defined by the ability to inhibit phospholipid dependent coagulation reactions) and specificities for different conformations of phospholipids. Understanding these differences may be important in explaining the variations in clinical presentation of patients with these antibodies. This review attempts to define and discuss anticardiolipin heterogeneity.

Animals↗

A comparison of cardiac valvular involvement in the primary antiphospholipid syndrome versus anticardiolipin-negative systemic lupus erythematosus.

Recurrent thrombosis and pregnancy loss are well-recognized features of the antiphospholipid syndrome. Uncertainty exists, however, as to whether other reported features of the antiphospholipid syndrome such as cardiac valvular vegetations are truly part of this disorder or more reflective of associated systemic lupus erythematosus (SLE). Several recent studies have concluded that patients with antiphospholipid antibodies have a higher risk of developing Libman-Sacks endocarditis. This study was performed to determine whether antiphospholipid antibodies are the only risk factors for cardiac valvular disease in patients with primary antiphospholipid syndrome (PAPS) or SLE. Ten patients with PAPS were matched with 20 patients with SLE and 20 healthy control subjects by sex. All participants were tested for anticardiolipin (aCL) antibodies by means of a standardized enzyme-linked immunosorbent assay technique, and all underwent two-dimensional and color-flow Doppler echocardiography. The echocardiograms were interpreted by two cardiologists blinded to the patients' underlying disease. Sixty percent of the PAPS group had cardiac valvular involvement compared with 40% of the SLE group (p = NS). We conclude that cardiac valvular vegetations are common both in aCL-negative patients with SLE and in patients with PAPS. This suggests that aCL antibodies either play no causative role or are not the only risk factors in the development of cardiac valvular vegetations.

Adult↗

The effects of heparin and dietary fish oil on embolic events and the microcirculation downstream from a small-artery repair.

In recent studies we demonstrated that platelet emboli induced by arterial injury impair the microcirculation. The present study was performed to determine if heparin or dietary cod liver oil reduces the incidence of emboli following the same arterial injury and, in turn, whether these agents prevent the associated decrease in microcirculatory blood flow. The cremaster muscle of 29 male Sprague-Dawley rats was isolated on a single neurovascular bundle consisting of the iliac artery and vein and the genitofemoral nerve. Emboli were generated by a thrombogenic injury of the iliac artery, and their number and their subsequent effect on capillary perfusion in the downstream microcirculation were measured. Nine animals received heparin (10-unit IV bolus plus 10 units/hour IV infusion), 10 were fed cod liver oil (10 percent by weight of food) for 3 weeks prior to the experiment, and 9 animals receiving no treatment served as controls. The number of emboli was significantly reduced in the heparin group, but there was no accompanying improvement in capillary perfusion. In contrast, in the cod liver oil group, the number of emboli was not reduced, but there was significant improvement in capillary perfusion. These findings suggest that the harmful effect that platelet emboli have on the microcirculation is probably biochemical in nature (vasoconstriction) rather than related to simple mechanical obstruction to flow.

Anastomosis, Surgical↗