Correlations between structure and antimycobacterial activity in a series of 2-acetylpyridine thiosemicarbazones

The antimycobacterial activity of a new series of 2-acetylpyridine thiosemicarbazones was determined in vitro using Mycobacterium smegmatis ATCC 607. The resulting log minimal inhibitory concentration (mumol l-1) values were plotted against the partition coefficient (log P) values for each compound, and fell on a parabolic distribution curve having a log P opt of 3.0. Compounds having partition coefficients outside the range 2.0 to 4.0 were inactive against M. smegmatis. When similar assays were carried out using M. tuberculosis, M. kansasii, M. marinum, M. simiae, M. avium and M. intracellulare, a similar series of parabolic activity curves were obtained having log P opt values around 4.0. The significance of this shift in the log P opt value obtained using the slow-growing pathogenic mycobacteria compared to that observed with the rapid-growing M. smegmatis is discussed in relation to the structures of the variable substituents of these new 2-acetylpyridine thiosemicarbazone compounds.     

Maternal use of selective serotonin re-uptake inhibitors in early pregnancy and infant congenital malformations

BACKGROUND: Maternal use of selective serotonin re-uptake inhibitors (SSRIs) has recently been associated with an increased risk for certain malformations. METHODS: Using the Swedish Medical Birth Register, we identified women who had reported the use of SSRIs in early pregnancy and studied their infants, born between July 1, 1995 and the end of 2004. Congenital malformations were identified from that register, from the Register of Congenital Malformations, and from the Hospital Discharge Register. The effect of drug exposure was studied after adjustment for a number of identified maternal characteristics that could act as confounders. RESULTS: We identified 6,481 women who reported the use of SSRIs in early pregnancy and their 6,555 infants. There was no general increase in malformation risk. An increased risk for cystic kidneys was seen, but this was based on only nine malformed infants, and the pathology varied between these cases. An in-depth study of cardiovascular defects identified an association between such defects and notably ventricular and atrial septum defects and maternal use of paroxetine but not other SSRIs. No support for a postulated association between SSRI use and infant craniostenosis or omphalocele was found. CONCLUSIONS: Use of SSRIs in early pregnancy does not seem to be a major risk factor for infant malformations. The association between paroxetine use and infant cardiovascular defects may be a result of multiple testing, but is supported by other studies.     

Cytogenetic study of the chorion and placenta in prenatal diagnosis of fetal pathology]

The experience of investigation of 230 chorion and placental biopsy in 209 women of high risk pregnancy group is presented. Two methods of "direct" chromosomal analysis have been compared. Prospects and high economic efficiency of chorion and placenta studies as against other methods of prenatal diagnosis, great role in a decrease of prenatal disease and mortality are confirmed.     

Periodicity and time trends in the prevalence of total births and conceptions with congenital malformations among Jews and Muslims in Israel, 1999-2006: a time series study of 823,966 births

BACKGROUND Congenital malformations (CMs) are a leading cause of infant disability. Geophysical patterns such as 2-year, yearly, half-year, 3-month, and lunar cycles regulate much of the temporal biology of all life on Earth and may affect birth and birth outcomes in humans. Therefore, the aim of this study was to evaluate and compare trends and periodicity in total births and CM conceptions in two Israeli populations. METHODS Poisson nonlinear models (polynomial) were applied to study and compare trends and geophysical periodicity cycles of weekly births and weekly prevalence rate of CM (CMPR), in a time-series design of conception date within and between Jews and Muslims. The population included all live births and stillbirths (n = 823,966) and CM (three anatomic systems, eight CM groups [n = 2193]) in Israel during 2000 to 2006. Data were obtained from the Ministry of Health. RESULTS We describe the trend and periodicity cycles for total birth conceptions. Of eight groups of CM, periodicity cycles were statistically significant in four CM groups for either Jews or Muslims. Lunar month and biennial periodicity cycles not previously investigated in the literature were found to be statistically significant. Biennial cycle was significant in total births (Jews and Muslims) and syndactyly (Muslims), whereas lunar month cycle was significant in total births (Muslims) and atresia of small intestine (Jews). CONCLUSION We encourage others to use the method we describe as an important tool to investigate the effects of different geophysical cycles on human health and pregnancy outcomes, especially CM, and to compare between populations.     

Clonazepam use in pregnancy and the risk of malformations

BACKGROUND: Clonazepam (Klonopin) is a benzodiazepine that has been used widely to treat seizures and conditions such as panic attacks and anxiety disorder. However, the current findings about its use in pregnancy are derived from limited studies of small sample size. Because it is commonly prescribed during pregnancy, more information about its safety is needed. METHODS: The medical records of 28,565 infants were surveyed as part of a hospital-based malformation surveillance program to identify those who had been exposed prenatally to an anticonvulsant, including clonazepam. RESULTS: During a 32-month period, 166 anticonvulsant-exposed infants were identified; 52 had been exposed to clonazepam, 43 as monotherapy. A total of 33 (76.7%) of the monotherapy infants were exposed during the first trimester. One (3.0%) infant had dysmorphic features, growth retardation, and a heart malformation (tetralogy of Fallot). CONCLUSIONS: This study did not observe an increase in major malformations in births exposed to clonazepam monotherapy. However, this study is not large enough to have adequate power to determine whether or not the rate of major malformations is increased in clonazepam-exposed pregnancies. No increase has been identified in three other case series. Although the number of patients in this series was larger than previous reports, continued monitoring of pregnancies is needed to determine whether or not clonazepam is teratogenic.     

Peroxidase activity in the mouse uterus, placenta and fetus during pregnancy

Changes in peroxidase activity during pregnancy were examined in CD-1 mice. Peroxidase activity was measured with guaiacol as the substrate in uterine extracts of nonpregnant mice and in uterine, placental, and fetal extracts of pregnant mice on days 9, 12, 14, 16, and 18 of gestation. Uterine peroxidase activity in nonpregnant mice was high, but declined logarithmically to only 0.2% by day 18 of pregnancy. In contrast to this decline, a concomitant 50-fold logarithmic increase in fetal peroxidase activity was observed between day 12 and 18. Activity in placental extracts did not change significantly throughout the gestational period examined. These results suggest that membrane bound peroxidase in mouse uterus and fetus undergoes major shifts during pregnancy.     

Production and reception of growth factors in placenta during physiological pregnancy and the pregnancy, complicated with gestosis

30 women with physiological pregnancy and 28 women with gestosis were examined. The content of epidermal growth factor (EGF), vascular-endothelial growth factor (VEGF) and their receptors were studied in the early chorion obtained after abortion and in the full-term placenta using the ELISA method. The process of normal gestation was characterized by the increase of the placental production both of the EGF and VEGF. During the pregnancy complicated with gestosis and miscarriage in the first trimester the content of EGF and its receptor was lower compared to the physiological values. For VEGF and its receptor opposite changes were found: the increase of quantity of the growth factor and the decrease of its receptor. In the case of gestosis and term of pregnancy the content of the both growth factors and their receptors was lower than in corresponding controls. The changes in production of the angiogenic growth factors and their receptors in the placenta may have the pathogenic importance in the development of gestosis.     

Morphohistochemical study of the rat placenta administered a hepatotropic poison at different periods of pregnancy]

Intragastric administration of CCl4 (0.3 ml per 100 g of body weight) to female rats caused a marked injury of the placental tissue and particularly of the chorionic epithelium of the labyrinthine portion with the maximal development of dystrophic necrobiotic processes on the 14th-16th day of pregnancy (when the poison was administered 48 hours before the animal was sacrificed). There was noted an increase in the number of mitoses in the epithelial cells at all the periods, and a statistically significant enlargement of the nuclei and the nucleoli of the cytotrophoblastic cells on the 17th--18th day of the intrauterine fetal development. CCl4 administration led to the reduction in the content of histochemically detectable glycogen in the cytoplasm of the chorionic epithelium and to the fall in the amount of amylase-resistant glycoproteins, protein and RNA in dystrophically altered cells.