N-substituted benzamides inhibit NFkappaB activation and induce apoptosis by separate mechanisms.

Benzamides have been in clinical use for many years in treatment against various disorders. A recent application is that as a sensitizer for radio- or chemotherapies. We have here analysed the mechanism of action of N-substituted benzamides using an in vitro system. We found that while procainamide was biologically inert in our system, the addition of a chloride in the 3' position of the benzamide ring created a compound (declopramide) that induced rapid apoptosis. Furthermore, declopramide also inhibited NFkappaB activation by inhibition of IkappaBbeta breakdown. An acetylated variant of declopramide, N-acetyl declopramide, showed no effect with regard to rapid apoptosis induction but was a potent inhibitor of NFkappaB activation. In fact, the addition of an acetyl group to procainamide in the 4' position was sufficient to convert this biologically inactive substance to a potent inhibitor of NFkappaB activation. These findings suggest two potential mechanisms, induction of early apoptosis and inhibition of NFkappaB mediated salvage from apoptosis, for the biological effect of N-substituted benzamides as radio- and chemo-sensitizers. In addition it suggests that N-substituted benzamides are potential candidates for the development of anti-inflammatory compounds using NFkappaB as a drug target.

[The volume and present methods of legal abortion in children and adolescents at the Gynecology Clinic in Novi Sad 1985-1995]. / Obim i savremene metode legalnog prekida trudnoce u decijem i adolescentnom dobu na Ginekoloskoj klinici u Novom Sadu u periodu 1985-1995. godine.

Legal pregnancy interruptions in juvenile and adolescent age performed at the Department of Obstetrics and Gynaecology in Novi Sad, during the period from 1985 to 1995, have been analyzed and presented. The authors point out the following methods of choice for pregnancy interruptions: interception to 7 weeks of pregnancy, electric vacuum aspiration from 8 to 13 weeks of pregnancy, a combination of parenteral and local application of prostaglandins from 14 to 20 weeks of pregnancy.

Intra-amniotic Chlamydia trachomatis infection.

Chlamydia trachomatis is one of the most prevalent genital pathogens in pregnant women. Ascending, transcervical infection may reach fetal membranes creating chorioamnionitis or amniotic fluid infection. The aim of this study was to examine amniotic fluids obtained during cesarean section for the presence of chlamydial IgM- and IgG-specific antibodies, and for the presence of C. trachomatis antigen. Five of 52 (9.6%) amniotic fluid samples were seropositive. Two of 52 (3.8%) amniotic fluid samples had C. trachomatis antigen in the epithelial cells of the amnion. In conclusion, our data indicate that there is a high rate of transmission of C. trachomatis from mother to infant and that the pathogen can be identified in the amniotic fluid.

[Chlamydia trachomatis infection in newborn infants]. / Infekcija novoredjenceta uzrocnikom Chlamydia trachomatis.

The aim of our study was to examine the frequency of Chlamydia trachomatis infection in newborns by detecting specific antibodies, and to examine the Apgar score and the birth weight of Chlamydia trachomatis-antibody positive children. Fifty-two newborn infants were tested. High serum IgG chlamydial specific antibody titers had 11 (21%) newborns, while high serum IgM titers had 9 (17%) newborns. Our results showed that serum Chlamydia trachomatis-specific IgM antibodies were detected statistically more often in low birth weight newborns (<2500 g) (p < 0.05).

[Acute myeloblastic leukemia during pregnancy]. / Akutna mijeloblastna leukemija u trucnoci

We present a pregnant woman, with diagnosis of acute myeloblastic leukemia (AML) established in the third trimester of pregnancy. She was delivered by Caesarean section at the end of 36th gestational week, and a healthy, mature-for-date, male infant was born. Combined chemotherapy (YU-AML protocol) was administered a week after the delivery, but the patient died after 7 months, due to resistant disease. We discuss actual problems that make an approach to pregnant patient with AML specific and individual.

The estimation of fructosamine and HbAlc in pregnant women with diabetes mellitus.

Fructosamine, HbAlc, glucose, albumins and total proteins were estimated in 40 healthy pregnant women and 80 pregnant women with insulin dependent diabetes mellitus. Fructosamine was estimated by the NBT method with "Fructosamine test" commercially available kit on Technicom automatic analyser RA-1000. Glucose was determined on Beckman glucose analyser. HbAlc was assayed by the Bio-Rad test, while albumin and total proteins by Beckman tests. For all estimated parameters no significant differences were found between healthy pregnant women and pregnant women with insulin dependent diabetes mellitus.

[Etiologic factors in fetal intrauterine growth retardation]. / Etioloski cinioci kod intrauterusnog zastoja u rastu ploda.

The authors studied the incidence of individual aetiological factors which may cause intrauterine interruption of foetal development. The research concerned 26 pregnant women hospitalized in the Ward for Pregnancy Pathology of the Department of Gynaecology and Obstetrics over the period from 1986-1989. The majority of women with this manifested EPH gestosis: essential hypertension was observed in 3 patients (12%). Particular attention was paid to the final stage of delivery and to the Apgar Score. Discussion includes the results of other authors. In the conclusion the importance and significance of this problem are stressed--within the scope of perinatal medicine--in view of the high morbidity and mortality rates among infants.

[The determination of specific proteins in the biological fluids from pregnant women suffering from diabetes mellitus]. / Opredelenie spetsificheskikh belkov v biologicheskikh zhidkostiakh beremennykh, stradaiushchikh sakharnym diabetom.

An immunochemistry analyser has been used in testing a series of specific proteins (complement components C3 and C4, properdin, factor B, immunoglobulins G, M and A, alpha 1-antitrypsin, alpha 1-acid protein and alpha 2-macroglobulin) in biological fluids of normal and diabetic women in third-trimester pregnancy. Significant abnormalities in the protein spectrum were found in diabetes mellitus, a marker to be used in monitoring of diabetic pregnancies and control of therapy.

[Standard fetal growth curves--current aspects of their utilization]. / Standardne krive fetalnog rasta--savremeni aspekt njihovog koriscenja.

The total 3492 complete measurements were performed in order to make asymptomatic curves of intrauterine foetal development. Of this number 1756 measurements concerned the biparietal diameter (BPD) and 1736 the abdominal diameter (ABD). Measurements of the biparietal diameter were done from the 13th to the 41st week of gestation. The mathematical processing of all serial groups was done according to defined algorithm. On the basis of statistical analysis of distribution frequency and dispersion parameters the necessary findings were obtained. Thanks to these findings asymptomatic curves of intrauterine foetal development were made.

[Biopsy of the chorionic villi with the aid of ultrasound in the diagnosis of chromosome disorders in the 1st trimester]. / Biopsija horion frondozuma uz pomoc ultrazvuka u cilju otkrivanja hromozomopatija u I trimestru.

Chorion frondosum biopsy is a method of antenatal diagnosis based on the chorion villi cell analysis, with the aim of detecting hereditary disorders of chromosomal and genetic origin. The method was applied at the Department of Gynaecology and Obstetrics in women with undesired pregnancy from 8 to 12 weeks. This was the first phase of our investigation. Chorion frondosum samples were taken by Jackson's forceps and "Portex" cannula for transcervical aspiration. The role of ultrasound, as a component part of this method, is pointed out in the paper. Ultrasound was applied in a way not to damage the embryo and its membranes, and to locate chorion frondosum--the site of taking the appropriate chorionic villi. The success of detection of foetal chromosomal constitution in our study was 84%. Chromosomopathy was registered in on case. The foetus had tetraploidy--92, XXYY.

[Levels of immunoglobulins in various media from healthy pregnant women and women with diabetes mellitus and EPH gestosis]. / Vrednosti imunoglobulina u razlicitim mediumima kod zdravih trudnica, sa diabetes mellitusom i EPH gestozama.

The introduction deals with of the history, etiology and, briefly, clinical manifestations of endemic nephropathy. The authors state that a large number of investigations have been done until today, but without producing a diagnostic test for early diagnosis of the disease. This led the authors to pursue certain laboratory investigations. The control group consisted of 30 healthy individuals while patients diagnosed as Endemic Nephropathy were grouped according to stages of the disease: initial, developed, terminal stages. Nucleotides in erythrocytes (5' UMP, 5' IMP, 5' GMP, 5,CMP, 5' AMP, 5' ADP, 5' ATP) were determined on the Acidic Aminoanalyzer, with use of a special UV detector. Catecholamines in the urine were determined by using ratiofluorometery. Creatinine phosphocinase, hydroxybutirat--dehydrogenase and 2,3 DPG were determined on the "Carlbiochem" enzymometer. LDH, its isoenzymes as well as its profile were determined by electrophoresis on starch gel. Specific proteins such as haptoglobin, alpha 2 macroglobulin, alpha 1 antitrypsin, alpha 1 acid glycoprotein, properdin factor B, ceruloplasmin were determined on the Immunochemistry Analyzer. Total cholesterol and cholesterol in lipoproteins fractions VLDL, LDL and HDL were determined on the Cholesterol Analyzer. All results were evaluated statistically. Our conclusion is that they are interesting and contribute to the diagnosis of endemic nephropathy.

Respiratory gases and acid base parameter of the fetus during the second and third trimester.

Respiratory gases and acid base parameters were determined in the samples of fetal blood collected by cordocentesis from 70 patients with normal course of pregnancy, between 18th and 38th gestational week. The mean pH value was 7.386 +/- 0.05; partial pCO2 pressure -4.819 +/- 1.464 kPa; O2-5.712 +/- 1.24 kPa; bicarbonate 21.528 +/- 0.494 mMol/l; base excess -2.284 +/- 0.647 mMol/l and saturation 74.86 +/- 13%. Statistically significant negative correlation between gestational age and pH (r = 0.841, p less than 0.01) and partial O2 pressure (r = -0.961, p less than 0.01) was revealed. Partial CO2 pressure correlated significantly with gestational age (r = 0.923, p less than 0.01). The values of bicarbonate and base excess do not change significantly during gestation. Our own standards of examined parameters were formed.

The influence of anemia on respiratory gases and acid base parameters of the fetus.

Fetal blood samples were collected by cordocentesis from 82 pregnant women; 12 of whom had severe forms of Rh isoimmunization, while 70 comprised the control group. The mean hematocrit value in the group under investigation was 15.72 +/- 3.62% and indication of severe anemia. The pH value in this group was 7.31 +/- 0.06; pCO2 partial pressure 6.36 +/- 0.64; O2-2.65 +/- 0.89 kPa; bicarbonate 23.84 +/- 3.02 mMol/l: base excess was -2.72 +/- 2.66 mMol/l and saturation 28.66 +/- 15.56%. In the control group the following values were established: pH -7.386 +/- 0.05; partial pressure pCO2-4.980 +/- 0.31 kPa; O2--4.960 +/- 0.90 kPa; bicarbonate 21.560 +/- 0.27 mMol/l; base excess -2.30 +/- 0.90 mMol/l and saturation 67.23 +/- 11.60%. The pH, partial pressure O2 and saturation values were significantly lower, while partial pressure CO2 was significantly higher in the investigated group than in the control group. Bicarbonates and base excess do not change significantly in the presence of anemia. Fetal blood sampling carried out by means of cordocentesis is the most reliable method for assessment of the degree of fetal anemia. The values of acid base parameters and of blood gases are an indication of either respiratory, respiratory-metabolic or metabolic acidosis. The possibilities of prenatal diagnostics, undoubtedly, contribute to a significant reduction of perinatal mortality.

The complements and immunoglobulins in different media of healthy pregnant women and in pregnant women with increased blood pressure.

We have determined the levels of complement C3, C4 and immunoglobulin G, M, A in mothers' and cord blood serum. Parallelly properdin factor B and immunoglobulin G tests were done in urine samples. All estimations were performed on Immunochemistry Analyzer "Beckman". The investigations were made on 30 healthy pregnant women and 30 with arterial hypertension at the end of third trimester. In the mothers' serum C3 was not significantly changed. In the cord blood of healthy pregnant women it was 0.69 g/L. (SD 0.12) and in those with hypertension 0.38 g/L. (SD 0.15), which means significantly decreased. Complements C4 was not significantly increased in mothers' and cord blood serum. Properdin factor B was significantly increased in mothers' and cord blood serum (healthy pregnant women in serum 0.38 g/L., SD 0.07; with hypertension 0.48 g/L., SD 0.15; while in the cord blood serum of healthy women it was 0.14 g/L., SD 0.06; and hypertensive it was 0.22 g/L., SD 0.10). The same parameter was significantly decreased in the urine of healthy subjects 3.94 mg/L., SD 1.91; and in the hypertensive too, 2.42 mg/L., SD 0.90. The IgG level was significantly increased in the urine of healthy pregnant women 4.42 mg/L., SD 2.24; with hypertension 6.64 mg/L., SD 3.61. IgM was not significantly changed in mothers' and cord blood serum. IgA was significantly increased in the cord blood serum of healthy mothers', 0.02 g/L., SD 0.01, with hypertension 0.12 g/L., SD 0.05.

[Cordocentesis--a new diagnostic approach in modern perinatology]. / Kordocenteza--novi dijagnosticki postupak u savremenoj perinatologiji.

Between March 1987 and May 1988 by the technique of percutaneous ultrasound guided biopsy, 154 chordocenthesis in 117 pregnant women were carried out. The indications were: suspected genetic hematologic disease (7), rapid karyotyping (36), maternal infection (14), Rh-isoimmunization (42), possible fetal biochemical disease (18). The procedure was simple, the duration in the last 100 interventions less than 5 minutes. No severe maternal or fetal complications, such as spontaneous abortion, pre-term delivery, or fetal death, except 5 transient fetal bradycardias, were observed.

[Lecithin in the amniotic fluid in the determination of fetal lung maturity]. / Lecitin u amnionskoj tecnosti za odredivanje maturiteta fetalnih pluca.

A prospective study involved 90 patients divided into groups of high risk and risk pregnancies, which matched in age, parity and gestational age. Two methods for the amniotic fluid phospholipid analysis were compared. The value of lecithin was measured by the two phase UV enzyme method and the lecithin/sphingomyelin (L/S) ratio was determined by Gluck's method. The correlation of lecithin and the L/S ratio with gestational age did not prove statistically significant. No correlation was found between the lecithin concentration and L/S ratio on the one hand and the occurrence of the respiratory distress syndrome on the other. The increase of RDS in high risk pregnancies was not statistically significant. The lecithin concentration determination appeared to be a more specific method (37%) than the L/S ratio (19%), and the predictive value of the negative test also proved to be higher (94%) in relation to the L/S ratio (89%).

[Complement and immunoglobulin levels in pregnant women with EPH gestosis]. / Vrednosti komplementa i imunoglobulina kod trudnica sa EPH gestozama.

The authors determined C3 and C4 complements, factor B properdin and immunoglobulins G, M and A in 20 healthy pregnant patients and in 20 patients with EPH gestosis. The analysis was performed in mothers sera, umbilical sera and amniotic fluid, and properdin factor B and IgG in urine. They used the nonfellometric technique with immunochemistry analyzer. The C3 complement was very increased in the serum of mothers with EPH gestosis, and complement C4 was slightly increased in the serum of EPH gestosis, and complement C4 was slightly in the serum of EPH gestosis, and complement C4 was slightly increased in the serum of mothers and umbilical sera. Factor B properdin was very increased in mothers sera and decreased in urine. Higher concentrations of immunoglobulin G were found in umbilical sera than in mothers sera. Increased concentrations of sera in mothers, the umbilicus and urine were observed in patients with EPH gestosis. In these patients IgM was decreased in the serum of mothers and the umbilicus. IgM was decreased in the serum of mothers and significantly increased in umbilical sera. Significant changes in patients with EPH gestosis were noted.