Complement activation and its prognostic role in post-cardiac arrest patients.

Cardiac arrest causes generalized ischaemia/hypoxia, and subsequent resuscitation inflicts reperfusion injury, the pathology of which is not fully understood. Moreover, predicting the prognosis of comatose, post-cardiac arrest patients is a complex clinical challenge. We hypothesized that the extent of complement activation might be a reliable predictor of mortality in this population. Forty-six comatose cardiac arrest patients were enrolled into our prospective cohort study, conducted in a tertiary care university clinic. All subjects were cooled to 32-34 °C body temperature for 24 h and then allowed to rewarm to normothermia. All patients underwent diagnostic coronary angiography. On admission, at 6 and 24 h, blood samples were taken from the arterial catheter. In these, complement products (C3a, C3, C4d, C4, SC5b9 and Bb) were measured by ELISA in blood samples. Patients were followed up for 30 days; 22 patients (47.8%) died by the end of this period. We observed that complement activation (determined as the C3a to C3 ratio) was higher in non-survivors than in survivors at each time point. In the multivariate Cox regression analysis, the C3a/C3 ratio determined 24 h after the initiation of therapeutic hypothermia predicted 30-day mortality regardless of age, sex and the APACHE II score. Complement activation occurs in post-cardiac arrest patients, and its extent correlates with 30-day survival. The C3a/C3 ratio might prove useful for estimating the prognosis of comatose post-cardiac arrest patients.

Short-term prophylaxis in hereditary angioedema due to deficiency of the C1-inhibitor--a long-term survey.

BACKGROUND: Hereditary angioedema is a potentially life-threatening disorder, because edema occurring in the mucosa of the upper airways can lead to suffocation. The management of HAE consists of avoiding the triggering factors, prophylaxis, and the acute treatment of edematous episodes. Medical procedures can also provoke edematous attacks, and therefore, short-term prophylaxis (STP) is recommended before such interventions. Our aim was to evaluate the efficacy and safety of STP administered before medical procedures. METHODS: We conducted a retrospective analysis before and a prospective survey after establishing the diagnosis in a group of 137 (60 males, 77 females; 20 pediatric and 117 adult) patients with HAE. Both were implemented using questionnaires, patient diaries and hospital charts focusing on medical interventions provoking edematous attack, and the medicinal products (C1-INH concentrate, tranexamic acid, and danazol) administered for STP. RESULTS: Comparing surgical interventions performed without pre-event STP (in 39/89 patients before HAE was diagnosed), or after STP (in 3/55 cases after diagnosis), we found a significant (P < 0.0001, Fisher's exact test) reduction in the number of edematous episodes. Evaluating the efficacy of the drugs administered for STP revealed that C1-INH concentrate (Berinert(®) , CSL Behring, Marburg, Germany) was significantly (P = 0.0096, Fisher's exact test) superior to orally administered drugs in reducing the instances of postprocedural edema. None of the medicinal products caused adverse events potentially related to STP. CONCLUSIONS: STP reduces the number of postprocedural edematous episodes. C1-INH concentrate is safe and effective for prophylaxis. When this agent is not available, danazol is a potential alternative for prophylaxis before elective medical interventions.

Association of elevated serum heat-shock protein 70 concentration with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia: a case-control study.

Our aim was to investigate the association between serum heat-shock protein (Hsp) 70 concentration and hypertensive disorders of pregnancy. One hundred and forty-two pregnant women with hypertensive disorders (93 with preeclampsia, 29 with transient hypertension of pregnancy and 20 with superimposed preeclampsia) and 127 normotensive, healthy pregnant women were included in the study. Serum Hsp70 concentration was measured using enzyme-linked immunosorbent assay. The serum Hsp70 concentration was significantly higher in patients with transient hypertension of pregnancy, in preeclamptic patients and in patients with superimposed preeclampsia than in the control group (median (25-75 percentile): 0.66 (0.52-0.84), 0.55 (0.42-0.80), 0.61 (0.42-0.91) ng/ml vs 0.31 (0.27-0.39) ng/ml, respectively; P<0.001). Multivariate logistic regression analysis showed independent association of elevated serum Hsp70 level with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia. The difference in serum Hsp70 concentration between preeclamptic patients and the control group was statistically significant in each gestational age category. In the groups of preeclamptic and superimposed preeclamptic patients, there was no significant difference in serum Hsp70 concentration between mild and severe preeclamptic patients, between patients with late and early onset of the disease, as well as between preeclamptic patients without and with foetal growth restriction. In conclusion, serum Hsp70 concentration is elevated in transient hypertension of pregnancy, in preeclampsia and in superimposed preeclampsia. Circulating Hsp70 may not only be a marker for these conditions, but might also play a role in their pathogenesis. However, further studies are needed to explore its role in the pathogenesis of hypertensive disorders of pregnancy.

Lipoprotein (a) and plasminogen are immunochemically related.

Earlier studies demonstrated that lipoprotein (a), a lipoprotein of high atherogenicity, possesses proteolytic activity. In this report, we provide evidence that the lipoprotein (a)-specific antigen, apoprotein (a) is immunochemically related to plasminogen. This was demonstrated by polyclonal antisera from rabbit, sheep and horse, and with three monoclonal antibodies from mouse. Using immunospecific adsorbers against lipoprotein (a), all plasminogen could be adsorbed from lipoprotein (a)-positive and apparently lipoprotein (a)-negative plasma. As an additional similarity to plasminogen, lipoprotein (a) binds selectively to lysine-Sepharose, but with a somewhat lower affinity. In an assay system for measuring the fibrinolytic activity challenged with streptokinase, lipoprotein (a) prolonged strikingly the fibrinolysis time under certain experimental conditions.

Correlation of serum ghrelin levels with body mass index and carbohydrate metabolism in patients treated with atypical antipsychotics.

The prevalence of diabetes mellitus and metabolic syndrome is higher in patients with schizophrenia than in the normal population. Atypical antipsychotic drugs are used in psychiatry since the beginning of 1990. These drugs differ from the "typical" antipsychotics used previously, as they have less extrapyramidal side effects, and because of this they are tolerated better, but are associated with weight-gain and disturbances in carbohydrate metabolism. Ghrelin is an orexigen hormone partaking in body weight regulation. It is produced in the enteroendocrine P/D1 cells of the gastric mucosa and secreted to the circulation. The aim of our study was to determine ghrelin levels of atypical antipsychotic-treated patients in relationship with their body mass index (BMI) and carbohydrate metabolism. We measured the fasting serum ghrelin levels in 56 patients (male/female: 16/40, age mean+/-S.D.: 50.6+/-5.6 years) treated with atypical antipsychotics (clozapine, olanzapine, risperidon and quetiapine), and in 75 healthy control subjects, age and gender matched (RIA Linco, USA) in relationship with their BMI and their fasting and 75 g OGTT 120 min blood glucose values. The serum ghrelin levels of the patient group were notably higher (1333+/-659 pg/ml) than in the control group (368+/-103, p<0.0001; Mann-Whitney). We found no difference among the four antipsychotics in weight-gain, diabetes prevalence and the serum ghrelin levels. The BMI of the patient group was significantly higher (29.3+/-7.2 kg/m2 versus 24.3+/-3.7 kg/m2, p<0.0001; Mann-Whitney); 32% of them had blood glucose abnormality (18/56). There was no difference between the ghrelin levels in diabetic and non-diabetic patients. We found a significant negative linear correlation between the serum ghrelin and BMI (r=-0.35, p=0.0078; Spearman), the ghrelin and fasting blood glucose (r=-0.32, p=0.015) and OGTT 75 g 120 min blood glucose levels (r=-0.27, p=0.036). The orexigen effect of elevated serum ghrelin levels can contribute to the weight-gain and high diabetes prevalence associated with atypical antipsychotic treatment. The link between atypical antipsychotic treatment and elevated serum ghrelin levels is unknown so far, but a dysregulation of the central feedback mechanism can be hypothesised.

Frequencies of certain complement protein alleles and serum levels of anti-heat-shock protein antibodies in cerebrovascular diseases.

BACKGROUND AND PURPOSE: A strong correlation exists between the intensity of atherosclerotic alterations in different arteries. Marked differences exist, however, in the age and sex distribution and risk factors for coronary heart disease (CHD) and cerebrovascular disease (CVD). We therefore performed genetic and immunologic studies in patients with CVD. METHODS: We studied 292 patients with CVD (stroke or transient ischemic attack) and as control either 198 healthy blood donors and 485 healthy elderly (aged >60 years) people (genetic study) or 94 blood donors aged 45 to 60 years and 49 healthy elderly (aged >60 years) people (anti-heat-shock protein [hsp] measurements). Allele frequencies of 3 genes (C4A, C4B, and C3) encoding proteins of the complement system were determined by electrophoresis and immunofixation. Serum concentration of autoantibodies against 60-kDa heat-shock protein (anti-hsp60) was measured by the enzyme-linked immunosorbent assay method. RESULTS: Marked differences were observed between CVD patients and controls in the genetic studies. In the CVD patients aged >60 years, the frequency (11.3%) of the deficient allele of the C4B gene (C4B*Q0) was significantly (P:=0.0003) higher than that of the healthy controls (5.4%). By contrast, in the group aged 45 to 60 years, the frequency of the C4B*Q0 allele was lower in patients than in controls. Serum concentration of anti-hsp60 in the CVD patients did not differ from control values. CONCLUSIONS: In previous studies C4B*Q0 frequency was reported to be higher in CHD patients aged 45 to 60 years than in aged-matched controls. Moreover, high anti-hsp60 levels were found in CHD patients. These findings contrast with our present report of lower frequency of C4B*Q0 in CVD patients. Therefore, genetic and immunologic factors may at least partly explain the differences between the natural history and risk factors of CHD and CVD.

Platelet membrane fluidity in type IIA, type IIB and type IV hyperlipoproteinemia.

Fluorescence spectroscopy, a very sensitive index for measuring the biophysical properties of living cell systems, was used to examine the structural order of intact, resting, gel-filtered platelets from hyperlipidemic subjects (n = 48, 25-70 years) and normolipemic subjects (n = 34, 19-68 years). Fluorescence anisotropy (r[s]), which is inversely related to membrane fluidity, was estimated using 3 different fluorescent dyes, DPH, TMA-DPH, and 6-AS, known to label different regions of biological membranes. Increased membrane fluidity was observed in type IIB (n = 24, 36-62 yrs; r[s] = 0.0692 +/- 0.09) and type IV (n = 10, 33-57 yrs; r[s] = 0.058 +/- 0.006) hyperlipidemics in comparison to type IIA (n = 14, 25-70 yrs; r[s] = 0.086 +/- 0.019) and control subjects (n = 24, 28-68 yrs; r[s] = 0.079 +/- 0.012). The temperature dependency of r[s]-DPH values was significantly different (P less than 0.01) in platelets from type IIB and type IV patients compared to type IIA and control subjects of similar age. A significant positive correlation (P less than 0.005) between membrane fluidity and age was found only in healthy control subjects (n = 34, 19-68 yrs). Despite significant (P less than 0.01) differences in plasma lipid concentrations in hyperlipidemic patients and controls, significant ex vivo relations between membrane fluidity and lipoprotein concentrations, free fatty acid distribution, and increased age were found only in healthy control subjects. Plasma levels of thromboxane as well as serum selenium concentrations did not significantly differ between hypercholesterolemic, hypertriglyceridemic, and control subjects.

Anti-cholesterol antibodies (ACHA) in patients with different atherosclerotic vascular diseases and healthy individuals. Characterization of human ACHA.

In animal experiments the protective role of anti-cholesterol antibodies (ACHA) in the development of atherosclerosis has been demonstrated. Despite the fact that ACHA are present in the serum of healthy humans, no data on the occurrence of these antibodies in human diseases are available. We determined serum concentrations of IgG type ACHA by an enzyme immunosorbent assay in 600 patients with atherosclerotic vascular diseases (86 patients with peripheral occlusive atherosclerosis, 146 patients with cerebrovascular diseases, 341 patients with severe coronary heart disease (CHD) who received aorto-coronary by-pass, 27 patients with myocardial infarction who did not undergo by-pass operation), in 57 patient controls (complaints of CHD, without coronarographic alterations) and in 218 healthy individuals. ACHA were present in the sera of all persons tested. No serum cofactor is needed for the binding of human ACHA to solid phase cholesterol, binding can be inhibited dose-dependently by LDL and even more strongly with LDL/VLDL preparations purified from human serum. ACHA levels were found to be considerably lower in patients with peripheral occlusive atherosclerosis and cerebrovascular diseases compared with the levels in healthy individuals. By contrast, the ACHA levels of patients with CHD were considerably higher. No differences in the IgG subclass distribution and binding efficiency of ACHA in the sera of CHD patients and controls were found. Thus, our present findings indicate that both low and high ACHA production may be associated with different atherosclerotic vascular diseases.

High level of anticholesterol antibodies (ACHA) in HIV patients. Normalization of serum ACHA concentration after introduction of HAART.

Anticholesterol antibodies (ACHA) are natural antibodies against the 3beta-OH group of cholesterol. Since lipid disorders are common in HIV infection and HAART may further enhance dislipidaemia, we determined by using an ELISA method serum ACHA concentrations in HIV patients and healthy HIV-seronegative controls. ACHA levels were almost 4 times higher in the sera of 46 patients than in 110 controls. No difference in the specificity of ACHA was found between HIV-seropositive and HIV-seronegative sera. Binding of ACHA to cholesterol-coated plates from a HIV-seropositive serum was dose-dependently inhibited by preincubation with HIV-1(BA-L) preparation. Serum concentration of ACHA was significantly higher in the patients with low serum cholesterol levels than in those with normal cholesterol levels. HAART induced a marked drop of ACHA concentration. We found a significant negative correlation between the length of HAART and the ACHA levels. By contrast, HAART did not significantly influence total IgG concentration and titers of antibodies against 60 kD heat shock protein. Our findings indicate that high levels of ACHA in HIV-infection may contribute to the development of hypocholesterolaemia frequently observed in this disease.

Human brain microvessel endothelial cell culture as a model system to study vascular factors of ischemic brain.

Cerebral ischemia is caused by reduced blood supply at the microcirculatory level. In the microvessels, the main elements of the reperfusion injury following brain ischemia are the transformation of endothelial cell-surface from anticoagulant to procoagulant property, leukocyte adhesion, sludge or clot formation. There is a paucity of information on how hemostatic factors, cytokines, lipoprotein(a) (Lp(a)) and endothelin-1 (ET-1), being responsible for ischemic/reperfusion injury, interact with human brain microvessel endothelium (HBEC). There are no data furthermore about the expression of complement proteins of HBEC influenced by cytokines or fibrinolytic factors. Previously we established optimal conditions for culturing HBEC. Cell contraction induced by thrombin, plasmin, miniplasmin was recorded. The reassembly of F-actin was observed after thrombin treatment. ICAM-1 upregulation was measured following TNF-alpha, IL-1-alpha and thrombin incubation. Plasmin and miniplasmin downregulated the ICAM-1 in our cell culture system. Lp(a) modulated the thromboresistant cell-surface by reduction of t-PA and u-PA, but PAI-1 remained unchanged. Lp(a) modulated the ET-1 production by early increasing and late decreasing, in a bimodal manner. The increased secretion of ET-1 by cytokines (TNF-alpha, IL-1-alpha) was reduced in the presence of Lp(a). Gradual increase of complement proteins (factor H, factor B, C4) was induced by cytokines. Plasmin and miniplasmin augmented a rapid increase of C4. Some factors of complex relationship between regulators and modulators of endothelial adhesion molecules have been demonstrated in a human cell culture system prepared from brain microvessel endothelium. A unified concept of sequential events of ischemia/reperfusion in the brain has not yet developed.

Apolipoprotein E alleles in women with severe pre-eclampsia.

This study investigated the frequency of apolipoprotein E (apoE) alleles among women with severe pre-eclampsia. The presence of the three most common apoE alleles (epsilon 2, epsilon 3, epsilon 4) was determined by polymerase chain reaction-restriction fragment length polymorphism in three groups of white women: non-pregnant healthy (n = 101), pregnant healthy (n = 52), and pregnant with a diagnosis of severe pre-eclampsia (n = 54). The frequency of apo epsilon 2 was highest among women with severe pre-eclampsia (16.6%) followed by non-pregnant women (12.9%), and those experiencing a healthy pregnancy (10.6%). The higher frequency of the apo epsilon 2 allele detected among women with severe pre-eclampsia suggests that apoE may play a role in the development of pre-eclampsia.

Elevated serum semicarbazide-sensitive amine oxidase activity in non-insulin-dependent diabetes mellitus: correlation with body mass index and serum triglyceride.

Previous clinical studies reported elevated semicarbazide-sensitive amine oxidase (SSAO) activity in insulin-dependent diabetes mellitus (IDDM), but there are not sufficient data about SSAO in non-insulin-dependent diabetes mellitus (NIDDM). The present study was conducted to investigate serum SSAO activity in NIDDM patients compared with nondiabetic and IDDM patients. Serum SSAO activity in 61 patients with diabetes (n = 34 NIDDM and n = 27 IDDM) and 36 controls was determined using 14C-benzylamine as a substrate. NIDDM and IDDM patients exhibited higher SSAO activity compared with controls ([mean +/- SD] NIDDM, 164.60+/-69.43 pmol/mg protein/h, P<.0001; IDDM, 143.91+/-72.45 pmol/mg protein/h, P<.002; control, 91.46+/-28.11 pmol/mg protein/h). There was a significant positive correlation between serum SSAO activity and the body mass index (BMI), body weight, hemoglobin A1c (HbA1c), fasting plasma glucose, and triglycerides. Within the control group, SSAO correlated with total cholesterol levels. The progression and severity of diabetic complications such as angiopathy may be exacerbated by cytotoxic metabolites (e.g., formaldehyde and hydrogen peroxide) formed by SSAO. These results reveal the possibility that elevated serum SSAO activity in association with obesity and hyperlipidemia may be a cardiovascular risk factor in diabetes mellitus.

Binding of fibronectin to human lipoproteins.

High molecular mass adhesive glycoprotein plasma fibronectin binds to isolated HDL and LDL lipoprotein fractions in a solid phase radioimmunoassay. Mean dissociation constants of interaction of fibronectin and immobilized HDL and LDL lipoproteins isolated from eight patients with type IIa and type IV hyperlipoproteinemia are 7.8 +/- 3.2 X 10(-7) mol/l and 6.8 +/- 2.6 X 10(-7) mol/l, respectively. Fibronectin can also bind to HDL and LDL isolated from six healthy subjects with mean dissociation constants of 2.07 +/- 0.45 X 10(-6) mol/l and 2.25 +/- 0.48 X 10(-6) mol/l, respectively. The binding is not dependent on the presence of divalent cations. Fibronectin-lipoprotein interaction is inhibited by soluble lipoproteins. There is no observable interaction between fibronectin and VLDL fraction. Binding of fibronectin to HDL and LDL lipoproteins can have an in vivo significance, since the interaction may play a role in the metabolism, deposition of lipoproteins into the vessel wall and in atherogenesis.

Lipoprotein(a) concentration and phenotypes in primary biliary cirrhosis.

We studied a selected group of 39 female patients suffering from primary biliary cirrhosis (PBC). This disease is characterized by typical lipoprotein alterations and elevated concentrations of serum cholesterol. Despite the increased concentration of atherogenic lipoproteins, enhanced atherogenesis is not characteristic of PBC. Serum total cholesterol, triglycerides, HDL2 and HDL3-cholesterol concentrations were measured by enzymatic methods or in combination with precipitation procedures. Apolipoproteins were determined by using immunonephelometric methods. ELISA sandwich method was used for lipoprotein(a) determinations. Apoprotein(a) phenotyping (isoforms) was performed by Western blotting with specific antibodies. The concentrations of serum lipids, lipoproteins and apoproteins (AI, AII and B) were found in the range of earlier investigations. The serum lipoprotein(a) concentration did not differ between the PBC patients and control subjects (10.0/0.1-54/, median 2.55 vs. 11.5/0-75/, median 5.2 mg/dl). In the advanced stages of PBC we found a higher number of patients with low lipoprotein concentration (lower than 1 mg/dl). In patients with shorter durations and milder histological alterations high HDL2 cholesterol subfractions has been detected (stage I = 0.42 +/- 0.18, stage II = 0.53 +/- 0.29 and stage III = 0.62 +/- 0.41 vs. stage IV = 0.26 +/- 0.15 mmol/l, P < 0.05). Despite the elevation of atherogenic lipoproteins, high HDL2-cholesterol and normal lipoprotein(a) concentrations may be one of the reasons why patients with advanced PBC are not placed at increased risk for atherosclerosis.

Apolipoprotein E gene polymorphism frequencies in a sample of healthy Hungarians.

Apolipoprotein E (apo E) has been found to play an important role in lipid metabolism and has been associated with cardiovascular and neurodegenerative conditions. Hungarians have some of the highest rates of cardiovascular morbidity and mortality in the world. This study examines the distribution of apo E alleles and genotypes in a population of healthy ethnic Hungarian blood donors (n = 302). Male (n = 152) and female (n = 150) subjects ranging from 18 to 62 years of age (mean 37.0) were involved. To determine the frequency of apo E alleles, polymerase chain reaction followed by restriction length polymorphism was applied. The analyses of data showed that apo E allele epsilon3 had the greatest frequency in this group (0.807), followed by apo epsilon2 (0.104) and apo epsilon4 (0.087). The highest genotype frequency was found to be epsilon3/3 at 65.2% (n = 197) followed by genotype epsilon3/4 at 15.9% (n = 48), genotype epsilon2/3 at 15.2% (n = 46), genotype epsilon2/2 at 2.3% (n = 7), genotype epsilon2/4 at 1.0% (n = 3) and genotype epsilon4/4 at 0.4% (n = 1). The apo E frequencies found in this study appear to differ from an earlier study of blood donors, where the results are based on apo E phenotyping.

The association of serum lipoprotein(a) levels, apolipoprotein(a) size and (TTTTA)(n) polymorphism with coronary heart disease.

BACKGROUND: The association between lipoprotein(a) levels, apolipoprotein(a) size and the (TTTTA)(n) polymorphism which is located in the 5' non-coding region of the apo(a) gene was studied in 263 patients with severe coronary heart disease and 97 healthy subjects. METHODS: Lp(a) levels were measured by ELISA, apo(a) isoform size was determined by SDS-agarose gel electrophoresis, and analysis of the (TTTTA)(n) was carried out by PCR. For statistical calculation, both groups were divided into low (at least one apo(a) isoform with < or = 22 Kringle IV) and high (both isoforms with >22 KIV) apo(a) isoform sizes, and into low number (<10 in both alleles) and high number of (> or =10 at least one allele) TTTTA repeats. RESULTS: Lp(a) levels were higher (P=0.007), apo(a) isoforms size < or =22 KIV and TTTTA repeats > or = 10 were more frequent (P=0.007 and 0.01) in cases than in controls. Lp(a) levels were found to be increased with low apo(a) weight in both groups (both P<0.0001). In multivariate logistic regression analysis, only the Lp(a) levels (P=0.005) and (TTTTA)(n) polymorphism (P=0.002) were found to be significantly associated with CHD. CONCLUSION: Nevertheless, these results indicate that in CHD patients the (TTTTA)(n) polymorphism has an effect on Lp(a) levels which is independent of the apo(a) size.

Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema.

BACKGROUND: Hereditary angioneurotic oedema (HAE) is a rare cause of ascites. As acute abdominal attacks of the disease can mimic surgical emergencies, prompt and accurate diagnosis is essential. This study was undertaken to evaluate the usefulness of serial abdominal ultrasound (US) examinations. PATIENTS AND METHODS: Seventy patients with HAE were followed up for almost a decade. All patients presenting with an acute oedematous attack underwent abdominal US, which was then repeated 24 and 48 h after appropriate therapy. RESULTS: Twenty-two acute oedematous attacks with abdominal complaints severe enough to justify hospital admission occurred in the study population. Abdominal US performed during the attack showed oedematous thickening of the intestinal wall in 80% of cases and invariably demonstrated the presence of free peritoneal fluid in all patients. Rapid symptomatic relief achieved by treatment was accompanied by the significant regression of US abnormalities. CONCLUSIONS: Transitory ascites demonstrated by abdominal US is a clue to the diagnosis of an acute abdominal attack of HAE. The possibility of HAE should always be considered whenever unexplained abdominal pain recurs with or without ascites.

Maternal and neonatal outcome of preeclamptic pregnancies: the potential roles of factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase.

OBJECTIVE: To investigate the potential perinatal effects of Factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase C677T polymorphism in preeclamptic women. STUDY DESIGN: One hundred twenty preeclamptic women (N = 120) and 101 healthy pregnant controls (N = 101) were recruited and evaluated for frequency of Leiden and 5,10 methylenetetrahydrofolate reductase (MTHFR) mutations using polymerase chain reaction (PCR). Perinatal outcomes were then recorded and analyzed for all study participants and their neonates. RESULTS: Laboratory analysis yielded 22 (18.33%) heterozygous carriers of Factor V Leiden mutation among preeclamptic women and 3 (2.97%) heterozygous carriers among the healthy controls; differences between the two groups were found to be statistically significant [p < 0.001, the relative risk (RR) = 6.17, 95% confidence interval (95% CI) = 1.90-20.02]. Homozygous MTHFR mutations were found in 8 of 120 (6.67%) preeclamptic women and in 6 of the 101 (5.94%) healthy controls evaluated. Among preeclamptic women, episodes of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome were reported in 7 of 22 (31.81%) of those with Factor V Leiden mutation and in 11 of 98 (11.22%) of those who were negative for the mutation. Group differences were determined to be statistically significant (p < 0.015, RR = 2.83, 95% CI = 1.24-6. 48). Perinatal indicators collected from the two groups included frequency of intrauterine growth retardation, birth weight, and gestational age. No statistically different perinatal outcomes were found between Factor V Leiden positive and negative preeclamptic women. In addition, MTHFR gene polymorphism did not appear to be correlated with the development of preeclampsia. CONCLUSION: Although the frequency of Factor V Leiden mutation appears to be significantly higher among preeclamptic women, the mechanism of pathogenesis and potential influence on perinatal outcomes is not yet well understood. Relatively high rates of HELLP syndrome among those with Factor V Leiden mutation suggest that this thrombogene mutation may play a significant role in hemostatic system activation. Our results suggest that the role of MTHFR polymorphism and other factors such as folic acid supplementation will require more extensive analysis in controlling worldwide morbidity and mortality associated with this important maternal condition.

Determination of human serum semicarbazide-sensitive amine oxidase activity: a possible clinical marker of atherosclerosis.

Semicarbazide-sensitive amine oxidase (SSAO) is present in the plasma membrane of several human tissues, e.g. vascular smooth muscle cell adipocytes, and is also found in human serum. Some previous studies on cultured endothelial cells indicate that cytotoxic metabolites (e.g. hydrogen peroxide, formaldehyde, acrolein) formed by serum SSAO may cause endothelial injury and subsequently induce atherosclerosis. To investigate the role of this enzyme in the pathogenesis of macrovascular complications in diabetes, a simple and sensitive radiometric procedure was adapted for human serum measurements. Serum SSAO activity of 35 patients with non-insulin dependent diabetes mellitus (NIDDM) and that of 30 controls was determined using [14C]-benzylamine as substrate. The severity of atherosclerosis was assessed by carotid sonography. Diabetic patients with atherosclerosis exhibited a higher SSAO activity compared to diabetic patients without complications (212.91 +/- 90.54 pmol/mg protein/h versus 133.17 +/- 65.40 pmol/mg protein/h, P <0.04). In diabetic patients without complications, serum SSAO activity was elevated compared to control subjects (133.17 +/- 65.40 pmol/mg protein/h versus 91.79 +/- 31.70 pmol/mg protein/h, P <0.01). These results suggest that determination of human serum SSAO activity might be a useful marker in the prognostic evaluation of diabetic angiopathy and atherosclerosis.

Physiological and clinical importance of lipoprotein(a).

Lipoprotein(a) is a genetically regulated trait, and its concentration in serum seems to be independent from that of other lipoprotein classes. It can be detected by ultracentrifugation in the d = 1.05-1.12 g/ml density range. Based on epidemiological observations Lp(a) is an independent risk factor for coronary heart disease. Its structure resembles LDL, but contains, in addition to apolipoprotein B 100, the disulphide-linked apoprotein(a). Apoprotein(a) shares a striking homology with plasminogen, consisting multiple repeating domains similar to kringle IV, a single kringle V and an inactive protease segment. The heterogeneity of Lp(a) complex is determined by the apoprotein(a) moiety. It seems so, that atherogenic properties of Lp(a) can be explained by its binding to glycosaminoglycans and inhibition of fibrinolysis. This latter effect is carried out by the kringle domains, which can interact with the plasminogen activators and plasmin binding sites on endothelial surface. The atherogenic properties of Lp(a) are expressed over 30 mg/dL serum concentration. Well-known antilipidemic drugs do not affect its serum level and genetically determined phenotype. Diseases leading to secondary hyperlipoproteinemia may influence the lipoprotein(a) level, too.