Low placental angiotensin-converting enzyme expression is related to fetal small for gestational age but not to metabolic control in type 1 diabetic pregnancies.

The maternal renin-angiotensin system is involved in blood pressure control and plays a crucial role in fetoplacental nutrition. Pre-gestational type 1 diabetes (PGDM) leads to serious pregnancy complications. We thus performed a longitudinal study to analyse the association of maternal angiotensin-converting enzyme (ACE) serum levels and placental mRNA expression with fetal newborns gestational weight in type 1 diabetes mellitus (T1DM) women. We recruited 65 singleton pregnant women with T1DM. Placental mRNA ACE gene expression was examined using quantitative real-time PCR. Serum ACE levels were measured in the first, second and third trimesters of pregnancy by ELISA commercial kits. Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers (0.55±0.06 vs 0.78±0.06 and 0.85±0.07 respectively, p=0.003). In the SGA group, the mRNA expression of ACE positively correlated with maternal body mass index (BMI) in the third trimester (r=0.49; p=0.04). In all study groups maternal ACE level was significantly higher in the third trimester (mean 139.91±SD 69.64) compared to the first and second trimesters of pregnancy (13.57±4.32 and 15.69±15.92 respectively). Our data suggest that lower placental ACE gene mRNA expression may have a vital role in the etiology of SGA babies.

Glucose evaluation trial for remission (GETREM) in type 1 diabetes: a European multicentre study.

OBJECTIVE: Strict metabolic control during the 1st year of type 1 diabetes is thought to be a key factor for achieving clinical remission. The aims of this study were two-fold: (i) to evaluate the frequency and duration of spontaneous remission (defined according to the parameters issued by the International Diabetic Immunotherapy Group (IDIG)) in a European population of consecutive recent onset type 1 diabetes patients (aged 5-35 years), followed-up for a period of 36 months with a common protocol of intensive insulin therapy and without adjunct immune-intervention; and (ii) to identify the predictive factors for clinical remission. RESEARCH DESIGN AND METHOD: A total of 189 consecutive patients with newly diagnosed type 1 diabetes according to ADA criteria were recruited in participating centres (Belgium, Czech Republic, Estonia, France, Germany, Hungary, Italy, Poland, Romania, Sweden and Turkey) and followed-up for a period of up to 36 months. In all patients, intensive insulin therapy was implemented consisting of three or four injections of regular insulin daily with NPH insulin at bedtime. Adjustment of insulin dose was made according to a common protocol. Various clinical characteristics (age, gender, severity of presentation, etc.), history (presence of diabetic siblings in the family, etc.) and integrated parameters of metabolic control (HbA(1c), blood glucose, the total insulin dose at hospital discharge adjusted for body weight) were collected. RESULTS: Twenty-two patients (11.6%) experienced remission. The median duration of remission was 9.6 months and the range was 31 months. There was a wide variation among centres. Logistic regression analysis focused on the centre as the main variable in achieving remission. CONCLUSION: Remission was shown to be very heterogeneous between centres depending on 'other factors' such as patient care and family awareness of the disease rather than on 'measurable factors' such as sex, age, HbA(1c) and severity of presentation at diagnosis. Using intensive insulin therapy and optimisation of metabolic control, remission occurred in nearly one out of eight patients.

The role of genetic factors in the pathogenesis of neonatal intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) affects 15-20% of babies born before 32 weeks of pregnancy. Besides gestational age (below 32 weeks) there are a number of IVH risk factors. Increasing attention is being paid to genetic factors in the development of IVH. The authors discuss genetic factors (mutations of coagulation factors, gene polymorphisms in pro-inflammatory cytokines, mutation of type IV collagen gene, polymorphisms of genes responsible for the regulation of systemic blood pressure and cerebral blood flows) whose involvement in IVH pathogenesis has been confirmed in the highest number of reports and for which being a carrier plays an important role in their pathophysiology. The role of genetic factors in IVH remains unclear. Further analysis of the role of genetic factors in the pathophysiology of IVH will make it possible to determine the group of newborns who are specifically at risk of developing IVH in the perinatal period.

Mutations in the human paraoxonase 1 gene: frequencies, allelic linkages, and association with coronary artery disease.

Oxidative damage is a major cause of atherosclerosis. Since human paraoxonase has been postulated as a factor which plays a role in protection from low density lipoprotein oxidation, recent studies have dealt with the impact of hereditary PON1 gene polymorphisms as risk factors for coronary artery disease (CAD). The results from these studies are conflicting. In a case-control study, 1000 Caucasian patients with angiographically confirmed CAD were recruited and matched by age and gender to 1000 control individuals. PON1 mutations in codons 55 and 192 were evaluated by polymerase chain reaction-restriction fragment length polymorphism and allocated to defined haplotypes *1 (55L/192Q), *2 (55L/192R), and *3 (55M/192Q). Frequency of PON1 genotypes without any mutation (PON1*1/*1, wild-type) in CAD cases was 16.9% versus 17.1% in control individuals. PON1*2/*2 showed a frequency of 6.6% versus 7.3% (P = 0.68 compared to wild-type), and PON1*3/3 occurred in 11.8% in CAD cases versus 10.3% among control individuals (P = 0.40). There was also no difference in the distribution of carriers heterozygous for *2 or *3 among cases and control individuals. A haplotype containing both mutations 55M and 192R was not observed. None of the investigated genotypes demonstrated association with early manifestation, severity of disease, acute coronary syndromes, or myocardial infarction. Logistic regression analysis with adjustment for age, gender, diabetes, hypertension, hypercholesterolemia and smoking revealed no evidence of increased coronary risk associated with PON1 genotypes. These results suggest that PON1 polymorphisms are not major genetic determinants of CAD.

Influence of imipramine on the circulatory system in the course of endogenous depressive syndromes. I. Evaluation of the basic parameters of the circulatory system.

In patients with endogenous depression, imipramine exerts a regulative effect in both directions on blood pressure and pulse rate, dependent on the starting levels. In a majority of patients treated with imipramine, after 14 days blood pressure dropped and pulse rate was slowed. Remission of endogenous depression was statistically significantly more frequent in patients treated with imipramine in whom pressure and pulse rate underwent normalization. Early appearance of these effects of imipramine in patients with endogenous depression seems to be a good prognostic index.

The influence of some antidepressant drugs on cardiac function. III. Influence on the isolated heart and isolated coronary blood vessels.

Imipramine, nortriptyline and amitriptyline reduced coronary flow in experiments on the isolated heart muscle and raised the tone of isolated coronary blood vessels.

The influence of some antidepressant drugs on cardiac function. IV. Influence of blood supply of the heart in situ.

In in situ experiments with cats, impiramine, nortriptyline and amitriptyline depressed arterial blood pressure, diminished coroncary flow and amplitude of the heart's contraction, and slowed cardiac action.

Influence of imipramine on the circulatory system in the course of endogenous depressive syndromes. II. Influence of imipramine on vascular reflexes.

In patients with endogenous depression imipramine normalizes vascular responses in vegetative tests (orthostatic test, Schellong's test, cold pressor test). The highest percentages of normal vegetative tests during treatment with imipramine were observed in patients in remission of symptoms of depression. The orthostatic tests seem to have the highest diagnostic value. In tests based on measurement of surface temperature imipramine improved function of the vascular system.

Influence of some antidepressant drugs on the circulatory system. I. Imipramine.

Imipramine exerts various, dose-related, effects on arterial blood pressure. A distinct hypotensive effect occurs at dosses of at least 0-5 mg/kg body weight. At lower dosage, the action of the drug is biphasic. In experiments in situ with animals, imipramine diminished amplitude of the heart's contractions. Controlled respiration during experiments with imipramine reduced its toxicity. In decapitated animals the action of imipramine was the same as in animals with intact central nervous system. At all dosage levels its effect on blood pressure was biphasic. Blockade of the sympathetic, parasympathetic system and vegetative ganglia had no significant effect on the circulatory response to imipramine. Low doses of imipramine potentiated the hypertensive effect of noradrenaline, and high doses weakened it.

The influence of trazodone on the circulatory system in patients with endogenous depression. I. Basic circulatory parameters.

In patients with endogenous depression in remission, decline of systolic blood pressure and a statistically significant shortening of pulse time were found.

The influence of trazodone on the circulatory system in patients with endogenous depression. II. Influence on vascular reflexes.

In patients suffering from endogenous depression, Trazodone caused a tendency to normalization of results of Schellong's orthostatic test, the cold pressor test, and tests of thermoregulation.

Influence of the vaccine Polyvaccinum mite on the nasal mucosa.

The necessity of prolonged administration of the vaccine Polyvaccinum prompted this study on the effect of the preserving agent on the nasal mucosa. Buffered physiologic saline solution containing 0.1--0.4% phenol, and the vaccine containing 0.1--0.4% phenol or 0.01% merthiolate were applied for 12 weeks on the nasal mucosa of rabbits. The nasal mucosa, parenchymal organs and adrenals were studied macroscopically and histologically, and immunologic studies were made. On the basis of the results, preservation of Polyvaccinum mite with 0.4% phenol is suggested.

Intense acute phase response in ischemic patients.

The aim of this study was to estimate the qualitative and quantitative changes of acute phase proteins in patients suffering from coronary heart disease. The study was carried out on 74 patients and 12 healthy volunteers. The patients were divided into three groups as follows: patients with myocardial infarction (n=37), Group I--without heart failure, Group II--with heart failure (II-III NYHA), Group III--patients with unstable angina pectoris (n=35); controls-healthy volunteers (n=12). The immunological measurements were performed at the beginning of hospitalisation (point 0), after 4, 8, 12 and 72 h, and after 6, 9 and 12 days of hospitalisation. The concentrations of C-reactive protein (CRP), alpha1-acid glycoprotein (AGP) and alpha1-antichymotrypsin (ACT) were measured using rocket immunoelectrophoresis according to Laurell. Glycosylation profiles of AGP and ACT were determined using crossed affinity immunoelectrophoresis with Con A as ligand according to Bøg-Hansen. Between Groups I and II statistically significant differences were observed for all investigated parameters. Highest concentration values were observed for Groups II and III; for Group II they appeared earlier than for Group III. The maximal values for reactivity coefficients (AGP-RC and ACT-RC) were observed earlier than the respective maximal values of concentrations. Continuous activation occurring in unstable angina leads to a more rapid increase in the concentrations of acute phase proteins and more marked alterations in their glycosylation profiles. In a way these patients seem to be 'primed' with constant stimulation, so that they respond dramatically to the stimulus of ischemia.

Blood levels of alloxan in children with insulin-dependent diabetes mellitus.

Alloxan is a well-known and universally used agent for evoking experimental diabetes through its toxic effect on the B cells of the Langerhans islets. In our study, blood levels of alloxan in children with insulin-dependent diabetes mellitus were investigated. The observations were made in 68 children aged 6-15 years and in a control group of 44 healthy children in the same age range. Alloxan levels were estimated spectrophotometrically. The mean level of alloxan in blood from children with insulin-dependent diabetes mellitus was 8.76 +/- 9.64 micrograms/ml and in blood from healthy children was 1.53 +/- 1.10 micrograms/ml. The difference was statistically significant (P < 0.05). The metabolism of alloxan leads to the production of free superoxide radicals which, as is well known, injure cells and cause conditions conducive to the occurrence of diseases from autoimmunity. The results obtained suggest therefore that higher levels of alloxan in diabetic children are of significance in the onset of insulin-dependent diabetes mellitus.

Assessment of liver ability to biotransformation of antipyrine in uraemic patients on regular peritoneal dialysis treatment.

It was the aim of this work to establish whether biotransformation of drugs by the liver expressed by antipyrine kinetics is disturbed in peritoneally dialysed patients with end-stage renal failure. The investigations were carried out in 10 uraemic patients using the antipyrine test and comparing the parameters of antipyrine kinetics with those obtained in 13 healthy persons. Our results indicate that in uraemic patients on regular peritoneal dialysis treatment antipyrine kinetics are generally in the normal range, suggesting the microsomal content of cytochrome P-450 being not evidently reduced.

[Polymorphism of gene angiotensin converting enzyme in pregnancy induced hypertension]. / Polimorfizm genu kodujacego konwertaze angiotensyny i w nadcisnieniu indukowanym ciaza.

In the recent years genetic background of pregnancy induced hypertension (PIH) are intensively investigated. Genetically determined differences in activity of renin-angiotensin system (RAS) are of importance to hypertension susceptibility. The insertion/deletion (I/D) polymorphism of angiotensin I converting enzyme (ACE) was suggested to play an important role in the aetiology of idiopathic hypertension. We have tested if this polymorphism could be associated with PIH. ACE polymorphism was investigated in 87 pregnant women with PIH and in 110 healthy pregnant women (control group). Investigation was performed by polymerase chain reaction (PCR). We have amplified genomic DNA excteracted by phenol-chloroform method from blood leucocytes. We have detected overrepresentation of the I allele in the PIH group (47.2% and 41.4% in PIH and controls, respectively). ACE genotype frequency in control group was in agreement with expected values, according to Hardy-Weinberg law, but in the PIH group the obtained values were different from expected. This observation confirmed the possible role of I allele in aetiology of PIH, and we believe that continuation of this investigation is necessary.

[Triplet gestation--analysis of pregnancy course, delivery and neonatal outcome, based on personal material]. / Ciaza trojacza--analiza przebiegu ciazy, porodu, stanu noworodków, na podstawie materialu wlasnego.

UNLABELLED: Triplet gestation appears in 0.1-0.3% of all pregnancies and it is high risk pregnancy for mother and foetus. It appears more frequently in Afroamerican women, rarely in Japan women. In multifetal pregnancy early prenatal diagnosis and management are very important. AIM: Analysing course of pregnancy, way of delivery, condition of newborns, influence of environmental factors, and concomitant diseases in triplets gestation. MATERIAL: 30 women treated between 1989-1998, in Division of Perinatology, University of Medical Sciences in Poznan, Poland. RESULTS: 21 pregnancies were ended by caesarean section, 9 by vaginal delivery. Apgar score for II and III foetus decreases significantly. pH value of umbilical artery was without significant differences. CONCLUSIONS: Almost all triplets have ended preterm. Route of delivery of triplets have to be considered individually. Environment factors could play an important role in multifetal pregnancy.

[Cesarean section for the second twin during the course of delivering twins]. / Ciecie cesarskie na drugim plodzie w przebiegu porodu ciazy blizniaczej.

We have analysed 6 cases of twin pregnancies with vertex presentation of the first foetus. In this cases after delivery of the first twin by vaginal route caesarean, section was made. Caesarean section of the second twin was made because of: transversal presentation with fetal distress syndrom (four cases), umbilical cord drop (one case), and premature placenta ablation (one case). We have determined acid base balance and Apgar score. We have noted worse results for the second twin, independently too of the time between deliveries both twins. Caesarean section of the second twin is the rarely clinical situation, but in motivated situation is accepted and reasonable solution.

[Analysis of interleukin-6 serum concentration in trophoblastic tumors prognosis]. / Wartosc kliniczna analizy stezen interleukiny-6 u kobiet chorych na rozrosty i nowotwory trofoblastu.

OBJECTIVES: Our purpose was to estimate the prognosis based on Il-6 concentration in cases of trophoblastic tumors. MATERIALS AND METHODS: The study population was 65 women suffering from hydatiform mola or choriocarcinoma. We divided them into two groups: 30 patients who required only operative management and 35 patients who required operative procedures and additional chemotherapy. The observation period was 6 months. Blood samples were collected every 4 weeks. Concentration of Il-6 was measured in ELISA assay. RESULTS: The serum Il-6 concentration was significantly higher in cases of trophoblastic diseases than in the group of healthy women and higher in patients who required chemotherapy after operation (451.0 +/- 88.5 pg/ml), than in patients treated only surgically (257.1 +/- 77.1 pg/ml). CONCLUSIONS: Patients with hydatiform mola and choriocarcinoma reveal higher concentration of Il-6 than healthy women. It is associated with disease prognosis and allows to determine at the time of establishing a diagnosis, whether a patient can be treated only surgically or requires an additional chemotherapy.

[Gestational hypertension (GH) and a1166c polymorphism of angiotensin II type 1 receptor]. / Nadcisnienie ciazowe (GH) a polimorfizm A1166C receptora typu 1 angiotensyny II (AT1).

INTRODUCTION: Recent studies have suggested an association between genetic background of renin-angiotensin system (RAS) and the pathogenesis of pregnancy induced hypertension (PIH). However, the role of the gene coding for angiotensin II receptor (AT1) polymorphism in PIH is not fully understood, thus the aim of the present study was to determine the frequency of A1166C mutation in women with gestational hypertension (GH) and to establish the role of this polymorphism on the susceptibility to the PIH development. PATIENTS & METHODS: We have analysed 88 women with PIH and 113 healthy pregnant women as a controls. Genomic DNA was extracted from leucocytes using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). RESULTS: We have detected overrepresentation of mutated homozygous genotypes in the PIH group (11.4% in the PIH versus 2.7% in the controls). Homozygous wild-type genotypes were underrepresented in the PIH group (48.9% in PIH and 56.6% in controls). The frequency of heterozygotes was similar in both groups. Statistically significant overrepresentation of allele with mutation in the PIH group (31.3% in the women with PIH, and 23.0% in the controls) (O.R. = 1.5, p = 0.04) was observed. CONCLUSION: We suggest that presence of A1166C mutation is a risk factor for the development of PIH.