Prenatal dexamethasone exposure in the common marmoset monkey enhances gene expression of antioxidant enzymes in the aorta of adult offspring.

Human epidemiological studies have indicated that low birth weight associated with an adverse intrauterine environment is related to a greater incidence of cardiovascular disorders in later life. In the foetus, endogenous glucocorticoids generally increase if there is intrauterine nutrient deficiency. The consequent glucocorticoid hyperexposure has been hypothesised to cause in utero programming of atherogenic genes. We investigated the effect of oral treatment with the synthetic glucocorticoid dexamethasone during early or late pregnancy in marmoset monkeys on oxidative and antioxidant status in the offspring. Urinary concentrations of F(2)-isoprostanes were quantified as markers for in vivo oxidative stress. Expression of the mRNAs for the antioxidant enzymes cytosolic glutathione peroxidase (GPx-1), phospholipid hydroperoxide glutathione peroxidase (GPx-4), cytosolic Cu,Zn-superoxide dismutase (SOD1), mitochondrial Mn-superoxide dismutase (SOD2), glutathione reductase (GSR), modifier subunit of glutamate-cysteine ligase (GCLM) and catalase were determined in the aorta. Three groups of pregnant marmosets (10 animals per group) were treated orally for one week with vehicle, or with dexamethasone (5 mg/kg daily) during two gestation windows: early dexamethasone group, pregnancy day 42-48, and late dexamethasone group, pregnancy day 90-96. In one male sibling of each litter (10 males per group), aortas were taken at 2 years of age. In the late dexamethasone group a higher aortic mRNA expression for GPx-1 (p < 0.023), MnSOD (p < 0.016), GCLM (p < 0.019) and GSR (p < 0.014) in comparison to the controls was observed. Aortic expression in the early dexamethasone group was statistically significantly higher only for GSR mRNA (p < 0.038). No significant changes in urinary F(2)-isoprostane concentrations between controls, early and late dexamethasone groups at 2 years of age were observed. Hence, prenatal exposure to dexamethasone in the third trimester leads to increased mRNA expression of several aortic antioxidant enzymes in the offspring. This expression pattern was not temporally related to oxidative stress, and it may reflect in utero re-programming of aortic antioxidant gene expression during prenatal glucocorticoid exposure.

MDR1 haplotypes modify BEN disease risk: a study in Bulgarian patients with Balkan endemic nephropathy compared to healthy controls.

BACKGROUND: Balkan endemic nephropathy (BEN) is a slow progressive nephropathy with frequent occurrence of uroepithelial tumors in the upper urinary tract. Genetic factors involved in xenobiotic detoxification mechanisms may cause genetic predisposition to BEN and influence the risk for this disease. Polymorphic MDR1 variants with decreased P-glycoprotein (P-gp) activity modulate the risk for renal neoplasm. We have therefore investigated the impact of MDR1 polymorphisms on BEN manifestation. METHODS: The constitutional genotype frequencies of two SNPs (C3435T and G2677T) in the MDR1 gene in 112 healthy control subjects were investigated and compared with those of 96 patients with BEN. Identification of the SNPs was done with rapid cycle real-time PCR and melting curve analysis with allele-specific probes. RESULTS: The frequency of mutant alleles was comparable in both groups. Significant differences were revealed when the MDR1 haplotypes were analyzed. Individuals with a predicted haplotype 12 (2677G/3435T) were less frequent in BEN cases (frequency 7.3%) than in controls (16.1%, p = 0.006). We found that carriers of the haplotype 12 had a decreased risk for BEN (OR = 0.411; 0.21-0.78). CONCLUSIONS: The data suggest that haplotype 12 is protective against BEN. There is no clear molecular explanation of the MDR1 haplotype effects on the protein activity, which can explain the modified effect of the haplotype 12 on BEN risk.

[Rational method for prostaglandin use in cases with postpartal uterine hypotonia]. / Ratsionalen podkhod v upotrebata na prostaglandini pri sledrodova matochna khipotoniia.

The authors aim is to find out the most common dosages, roads of administration and the effect of 15-Methyl PgF2a (Prostin 15 M) during the treatment of postpartal uterine hypotony 1 to 3 amp. Of Prostin 15 M-1 ml. (250 mg Carboprost) were used deeply muscular, intracervical or intramyometrial, by 51 patients with postpartal hypotony. The most common risk factors associated with the development of postpartal haemorrhage are PIH, prolonged labour, the general anaesthesis and higli multiparity. The adequate treatment with Prostin 15 M woned reduse the life threatening complication in the Labour room. The most efficient is the intracervical way of administration, a good effect could be achieved even with 1 amp. Prostin 15 M when it is applied after the conventional methods and manipulations. The lacu of effect grow Prostin 15 M (in 5.88% in this study) shows that there is another pathology responsible for postpartal hemorrhage and life threatening hemorrhage and this usually requires Laparotomy. We offer every Obstetric Clinic to have 3 amp. Prostin 15 M available and these would spare a lot of negative feelings or emotions and it wont supply a better obstetric outcomes.

[For and against non-obstetrical indications for cesarean section]. / Za i protiv neakysherskite indikatsii za sectio caesarea.

The authors have made a retrospective study on the nonobstetrical indications for SC from 1996-2000 year, with the help of special documents belonging to VMI, Obstetric Clinic, Pleven. There have been 10,465 deliveries in the same period, 1096 with SC (10.47%). The main indications in 56 cases (5.11%) were non-obstetrical complications of pregnancy and delivery. The most frequent non-obstetrical indications were: ophthalmological in 18 (32.14%), orthopedical in 10 (17.86%), cases CNS diseases in 5 (8.93%) and cancer in 3 (5.36%). We have included: Condylomata accuminata--5 (8.93%), acute thrombophlebitis and thromboembolic diseases--5 (8.93%), a condition after plastic repairs of the perineum, virgin and vulvae--3 (5.36%). Special interest was taken on another group of patients with some rare diseases about the other specialist recommended SC. The ovarian age of the patients was 20-29 years--in 36 (64.28%). The SC has been performed in 30 cases (53.57%) in the first stage, in 14 (25.00%) in the second stage of delivery and in 12 (21.43%) cases was emergency. The conclusions of the authors is that the Obstetricians, who manage the delivery, may not always been comparted with that of the other specialist. This comes from the fact that the responsibility is mainly for him.

[Prostaglandin E2--an effective alternative for the induction of labor]. / Prostaglandin E2--efektivna alternativa za induktsiia na razhdaneto.

The authors aimed at studying the local application of PgE2 as a method of labor induction. 50 pregnant women divided into 3 groups were studied: I with Prostin E2 - vaginal tablets of 3 mg. Dinoprostone. II with Prepidil gel - 0.5 mg. Dinfprostone, applied intracervically and III with additional stimulation with Oxytocin - 5 E as an i.v. infusion. The criteria used were: parity, gestational age, Bishop score indications for induction. Success is considered as normal delivery by the 24th hour. Indications for PgE2 application are prematurity praeeclampsia, fetal malformations, fetal death, grave obstetrics history, RH incompatibility. It was discovered that with Prostin E2, the active phase of labor is reduced thus leading to reduction of labor. The frequency of operative deliveries also reduced and there were better fetal outcome. Two important advantages were discovered--simple application and physiologic advantages--the woman in labor is mobile and thus not traumatised. The authors stress that PgE2 application can be considered an effective method for labor induction.

[The characteristics of ureteral lithiasis]. / Niakoi aspekti ot kharakteristikata na ureternata litiaza.

The study covers 2630 patients with ureteral concrements, eliminated operatively, through extracorporeal lithotripsy (ESWL), or spontaneously as the result of drug treatment. Attention is called to the left-side location of ureteral concrements, regardless of the mode of elimination, with the clinical symptomatology of the disease being comprehensively discussed. Clinical and chemical characterization of ureteral concrements (type, size and the like) is also done separately with a special reference to the method of removal employed. In concrements eliminated spontaneously a correlative dependence with the annual season is sought; in the winter months a rather elevated frequency of elimination is recorded, irrespective of the type of concrements.

[The surgical and spontaneous elimination of kidney calculi--the type, incidence and treatment]. / Operativno i spontanno eliminirani bubrechni konkrementi--vid, chestota i lechenie.

Results are reported of chemical (derivatographic and polarization microscopic) analysis of 2630 calculi removed by operation and 8607 spontaneously eliminated calculi. It was found that 82.7 per cent of the calculi removed by operation and 19.4 per cent of those eliminated spontaneously were mixed--composed of two or more components. The most common "pure" concrements were composed from oxalates and uric acid. The difference in the chemical types of the renal calculi of the two compared groups (removed by operation and spontaneously) is shown and followed up. Of interest is the different incidence of the two calcium oxalate hydrates in the two compared groups of renal calculi. Vevelite was more common in calculi removed by operation, while vedeline was the more common form in spontaneously eliminated calculi. Precision of the chemical form of the calculosis is recommended, with a view to including the genesis of stone formation for effective prophylaxis, treatment and metaphylaxis of the disease.

[Electron microscopic study of calcium oxalate microcrystals]. / Elektronenmikroskopische Untersuchung von Calciumoxalatmikrokristallen im Urin.

Morphology and size distribution of calcium oxalate microcrystals in the urine of healthy people and calcium oxalate stone formers are examined by scanning electron microscopy. The data are compared with coulter-counter investigation and the following clinically important result is discussed. This initial crystal population be composed of single crystals and in sick people larger crystals have been found.