Pregnancy outcome following maternal exposure to statins: a multicentre prospective study.

OBJECTIVE: This contribution addresses the risk associated with exposure to statins during pregnancy. DESIGN: Multicentre observational prospective controlled study. SETTING: European Network of Teratology Information Services. POPULATION: Pregnant women who contacted one of 11 participating centres, seeking advice about exposure to statins during pregnancy, or to agents known to be nonteratogenic. METHODS: Pregnancies exposed during first trimester to statins were followed up prospectively, and their outcomes were compared with a matched control group. MAIN OUTCOME MEASURES: Rates of major birth defects, live births, miscarriages, elective terminations, preterm deliveries and gestational age and birthweight at delivery. RESULTS: We collected observations from 249 exposed pregnancies and 249 controls. The difference in the rate of major birth defects between the statin-exposed and the control groups was small and statistically nonsignificant (4.1% versus 2.7% odds ratio [OR] 1.5; 95% confidence interval [95% CI] 0.5-4.5, P = 0.43). In an adjusted Cox model, the difference between miscarriage rates was also small and not significant (hazard ratio 1.36, 95% CI 0.63-2.93, P = 0.43). Premature birth was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.019). Nonetheless, median gestational age at birth (39 weeks, interquartile range [IQR] 37-40 versus 39 weeks, IQR 38-40, P = 0.27) and birth weight (3280 g, IQR 2835-3590 versus 3250 g, IQR 2880-3630, P = 0.95) did not differ between exposed and non-exposed pregnancies. CONCLUSIONS: This study did not detect a teratogenic effect of statins. Its statistical power remains insufficient to challenge current recommendations of treatment discontinuation during pregnancy.

[Vaginal and postpregnancy inflamations, risks of their treatment for fetus]. / Rizika lécby vaginálních a poporodních infekcí a jejich bezpecnost pro plod.

OBJECTIVE: Paper describes risks of gynaecological inflamations and their treatment for the successful course of pregnancy. DESIGN: Review. SETTING: Czech Teratology Information Service, 3. LF UK, Praha. SUBJECT AND METHODS: The article refers the most common types of vaginal inflamation and gives recommendation for the appropriate treatment that is safe for embryo or fetus according to advice of Teratology Information Service. CONCLUSION: Vaginal inflamation during pregnancy represents risks of abortion, miscarriage or prematurity. For the treatment, we have to take in consideration the age of pregnancy and we should use the drugs, that are safe during this period. It is necessary always to compare risks resulting from disorder and from drugs used.

Development of the chick pancreas with regard to estimation of the relative occurrence and growth of endocrine tissue.

Endocrine cells in chick pancreas were observed to map their distribution during development and to perform morphometric studies starting on embryonic day 5. The ratio of exocrine to endocrine tissues first prevailed in favour of the endocrine ones, and changed abruptly after day 9 when rapid growth of exocrine tissue began. Endocrine tissue was formed of two types of islets. The 'light' (or B) islets were composed of insulin-immunoreactive cells, completed perhaps by a few somatostatin-immunoreactive cells occurring on the periphery. The majority of the somatostatin- and glucagon-immunoreactive cells were present in the 'dark' (or A) islets. Endocrine elements were also scattered as single cells over the pancreas. Sporadically, the endocrine cells established contacts with exocrine ducts. In morphometric analysis, volume density of insulin-, glucagon-, and somatostatin-immunoreactive cells was measured, and ratios were calculated between particular components. The volume density of endocrine cells and their ratio appeared stable in individual lobes but varied significantly between each other. Increase of the glucagon volume density is exponential, whereas insulin increases almost linearly especially in splenic lobe. The process results in the increase of the hormone-immunoreactive cell volume density in favour of glucagon-immunoreactive cells typical for birds.

Effect of Escherichia coli chaperonin GroELS on heterologously expressed human immunodeficiency virus type 1 reverse transcriptase in vivo and in vitro.

The two subunits of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (HIV-1 RT), p66 and p51, were coexpressed in Escherichia coli along with the E. coli chaperonin system GroEL/GroES. Coexpression increases the yield of heterodimeric HIV-1 RT by a factor of 4 to 5 and improves the nucleic acid binding affinity of HIV-1 RT by a factor of 1.6. We have analyzed the reasons for the improvements. The total increase in yield of HIV-1 RT can be attributed to an accumulation of RT subunits in the cells (factor of about 2.8) and an increased growth of the E. coli cells (factor of about 1.4). One reason for the accumulation in the cells is an improved stability of HIV-1 RT subunits toward bacterial proteases. In vitro studies showed that the nucleic acid binding affinity of HIV-1 RT purified from cells that did not coexpress GroELS was stimulated by adding purified GroELS (approx 1.5-fold), whereas HIV-1 RT stemming from cells coexpressing GroELS was stimulated only marginally (approx 1.1-fold). The in vivo as well as the in vitro studies suggest that the chaperonin interacts with HIV-1 RT and therefore affects the folding process of HIV-1 RT.

Structural changes of the Escherichia coli GroEL-GroES chaperonins upon complex formation in solution: a neutron small angle scattering study.

We applied neutron scattering in conjunction with deuterium (D-) labeling in order to obtain information about the domain structure of GroEL and GroES isolated and in the complex. Each subunit of the heptameric GroES consists of two domains, a core domain (Met1 to Lys15 and Lys34 to Ala97) and an intervening loop region (Glu16 to Ala33). Neutron scattering shows that both regions change their conformation upon GroEL/GroES complex formation. The interdomain angle between the core regions of the heptameric GroES increases from 120 to 140 degrees, leading to a less dome-like shape of GroES, and the loop regions turn inwards by 75 degrees. The 23 C-terminal amino acids of the 14 GroEL subunits (Lys526 to Met548), which are unresolved in the crystal structure, are located either at the bottom of the cavity formed by the seven-membered GroEL ring or at the inner wall of the cavity. Upon complex formation the apical domains of GroEL move outwards, which facilitates binding of GroES at a Gro-EL-GroES center-to-center distance of (87 +/- 8) A. These structural changes may be important for the dissociation of the unfolded protein bound to the central cavity upon GroES binding. The overall structure determined by neutron scattering in solution tallies with the crystallographic model published after completion of this study. Differences in the conformation of GroES observed in the complex by the two methods support the view that the chaperonin complex is a flexible molecule which might switch in solution between different conformations.

[Determination of the taxonomic position of bacteria from Lake Baikal using sequence analysis of 16S rRNA fragments]. / Opredelenie taksonomicheskogo polozheniia bakterii iz ozera Baikal metodom analiza posledovatel'nostei fragmentov 16S rRNA.

The taxonomic position of seven strains of aquatic bacteria from Lake Baikal was determined based on the analysis of the nucleotide sequences of 16 S rRNA gene fragments. Three strains belonged to the gamma-sub-class of Proteobacteria, one strain, to the beta-subclass, and the other three stains were assigned to the genus Bacillus (gram-positive bacteria with a low G+C content).

[Nucleotide sequence of a fragment of the Cottocomephorus grewingki phosphofructokinase gene]. / Nukleotidnaia posledovatel'nost' fragmenta gena fosfofruktokinazy Cottocomephorus grewingki.

The nucleotide sequence of a 208-bp fragment of the pfk gene encoding phosphofructokinase from Baikalian fish Cottocomephorus grewingki (Cottidae family) was determined. The fragment shows the codes of a sequence of 38 amino acid residues and contains a 94-bp intron. The nucleotide sequence of the C. grewingki phosphofructokinase gene and the corresponding amino acid sequence display the maximum homology to phosphofructokinases from rabbit muscles and a rat liver.

Eukaryotic DNA primase appears to act as oligomer in DNA-polymerase-alpha--primase complex.

Human placenta and calf thymus DNA-polymerase-alpha-primases were analyzed using native gradient-polyacrylamide-gel electrophoresis followed by overlay assays of polymerase and primase activities. The human enzyme contained three catalytically active native forms of 330, 440 and 560 kDa and the bovine enzyme five forms of 330, 440, 500, 590 and 660 kDa. Of the various DNA polymerase forms, only the largest (560 kDa for human DNA polymerase and 590 kDa and 660 kDa for bovine DNA polymerase) contained primase activity. Titration of human DNA-polymerase-alpha-primase with DNA-polymerase-free primase caused the conversion of the 440-kDa to the 560-kDa form. The data favour the idea that primase binds to DNA polymerase alpha as an oligomer of 3 primases/polymerase core. In addition, the ability of primase to utilize oligoriboadenylates containing (prA)n or pp(prA)n was investigated. The primase elongated pp(prA)2-7 up to nanoadenylates or decaadenylates, but did not add 9 or 10 mononucleotides to a preexistent primer. In contrast to pp(prA)n less than 10, (prA)n less than 10 were rather poor primers for the primase. Both pp(prA)8,9 and (prA)n greater than 10 were elongated by primase, producing characteristic multimeric oligonucleotides. The possible connection of the structure of the DNA-polymerase-alpha-primase complex with the catalytical properties of primase is discussed.

[Hypoxic stimulation and inspiratory resistive training in the rehabilitation of patients with chronic bronchitis]. / Gipoksicheskaia stimuliatsiia i inspiratornyi rezistivnyi trening v reabilitatsii bol'nykh khronicheskim bronkhitom.

A study was made of the efficacy of normobaric hypoxic stimulation (NHOS) and inspiratory resistive training (IRT) in multimodality treatment and rehabilitation of patients suffering from chronic obstructive bronchitis. The results were estimated by means of exercise tests and by stimulation electromyography of the diaphragm (SEMGD). The use of NHOS and IRT in multimodality treatment of the given group patients was found to give rise to a more complete physical rehabilitation of the patients, whereas the application of SEMGD is an effective approach to the control of sessions and courses of NHOS and IRT. Besides, the use of the latter method also permits choosing the intensity of the action of the treatment methods in question on the body, particularly on the diaphragm muscle.

[Functional state of the diaphragm during several non-drug methods of the treatment of chronic pulmonary insufficiency]. / Funktsional'noe sostoianie diafragmal'noi myshtsy pri nekotorykh nemedikamentoznykh metodakh lecheniia khronicheskoi legochnoi nedostatochnosti.

The study compared the effect of conventional therapy of aggravated chronic obstructive bronchitis (COB), inpatient oxygen treatment of large duration (OT), normobaric hypoxic stimulation (NBHS), inspiratory resistance on the diaphragmatic muscle function in COB patients with chronic pulmonary insufficiency. The function was assessed at stimulation electromyography of the diaphragm. The latter reflected enhanced bioelectric activity of the diaphragm in response to OT and inspiratory resistive training as shown by increased time parameters. Conventional COB treatment induced no changes in the myographic picture. Long-term response to NBHS needs further investigations.

Eukaryotic DNA primase. Abortive synthesis of oligoadenylates.

Calf thymus DNA polymerase alpha-primase, human placenta DNA polymerase alpha-primase and human placenta DNA primase synthesized oligoriboadenylates of a preferred length of 2-10 nucleotides and multimeric oligoribonucleotides of a modal length of about 10 monomers on a poly(dT) template. The dimer and trimer were the prevalent products of the polymerization reaction. However, only the oligonucleotides from heptamers to decamers were elongated efficiently by DNA polymerase alpha.

[The hospital stage of the long-term oxygen therapy of chronic lung failure in patients with chronic obstructive bronchitis]. / Statsionarnyi étap dlitel'noi kislorodoterapii khronicheskoi legochnoi nedostatochnosti u bol'nykh s khronicheskim obstruktivnym bronkhitom.

The authors analyze the role of the initial inpatient stage of long-term oxygen therapy (LOT) in combined treatment of chronic pulmonary failure in patients with chronic obstructive bronchitis, lung emphysema, and pneumosclerosis. The treatment lasted 30 days both in the main and in the control groups. In addition to basic therapy, the main group patients received 38% O2 for 15 h a day. To decrease the risk of PaCO2 elevation with a possible respiratory disorder, particularly in patients with initial hypercapnia, it is suggested that a special oxygen test with simultaneous control of acid-base balance and gas composition of the arterial blood may be carried out. In contrast to the control group, the main group patients demonstrated an improvement of gas composition of the arterial blood and of the parameters such as the alveolar-arterial gradient according to O2, the physiological pulmonary shunt. The combined use of oxygen therapy and resistance at expiration made it possible to ameliorate a number of external respiration function parameters, diffusion lung capacity, and enhanced the effect of oxygen therapy. It is shown that patients with PaO2 may be given LOT within the range of 60-69 mm Hg, provided the pulmonary physiological shunt exceeds 20%.