Early child health in Lahore, Pakistan: II. Inbreeding

The prevalence of consanguineous marriages was studied in 940 families belonging to four different socio-economic groups in and around Lahore, Pakistan. The births occurring in these families from September 1984 to March 1987 were also investigated for birth defects. The overall prevalence of consanguineous marriages was 46%. The first cousin marriages were most common (67%), followed by the marriages between second cousins, 19%. The prevalence of consanguineous marriages was clearly associated with the socio-economic status of the study groups; 50% of the marriages was related in the periurban slum, 49% in the village, 44% in the urban slum and 31% in the upper middle class. The birth defects were also more prevalent in the poorer areas, being highest in the periurban slum (17.7%) followed by the urban slum (15.6%) and then the village (14.8%) and lowest in the upper middle class (12.3%). Although, the frequency of both consanguinity and birth defects were related with the socio-economic levels of the study groups, there was no association between inbreeding and birth defects. Perhaps, deleterious recessive genes for birth defects have been 'bred out', because of continuous inbreeding over generations in this population. There was a significant predilection of major birth defects in boys without clear sex linkage. The conclusion is that the rate of consanguineous marriages was high, especially in the poorer areas, but the relationship between consanguineous marriages and birth defects was little or none. However, other child health indicators may be affected by consanguineous marriages.link_to_subscribed_fulltex

Effects of Cigarette Smoke Condensate on Oxidative Stress, Apoptotic Cell Death, and HIV Replication in Human Monocytic Cells

While cigarette smoking is prevalent amongst HIV-infected patients, the effects of cigarette smoke constituents in cells of myeloid lineage are poorly known. Recently, we have shown that nicotine induces oxidative stress through cytochrome P450 (CYP) 2A6-mediated pathway in U937 monocytic cells. The present study was designed to examine the effect of cigarette smoke condensate (CSC), which contains majority of tobacco constituents, on oxidative stress, cytotoxicity, expression of CYP1A1, and/or HIV-1 replication in HIV-infected (U1) and uninfected U937 cells. The effects of CSC on induction of CYP1 enzymes in HIV-infected primary macrophages were also analyzed. The results showed that the CSC-mediated increase in production of reactive oxygen species (ROS) in U937 cells is dose- and time-dependent. Moreover, CSC treatment was found to induce cytotoxicity in U937 cells through the apoptotic pathway via activation of caspase-3. Importantly, pretreatment with vitamin C blocked the CSC-mediated production of ROS and induction of caspase-3 activity. In U1 cells, acute treatment of CSC increased ROS production at 6H (>2-fold) and both ROS (>2 fold) and HIV-1 replication (>3-fold) after chronic treatment. The CSC mediated effects were associated with robust induction in the expression of CYP1A1 mRNA upon acute CSC treatment of U937 and U1 cells (>20-fold), and upon chronic CSC treatment to U1 cells (>30-fold). In addition, the CYP1A1 induction in U937 cells was mediated through the aromatic hydrocarbon receptor pathway. Lastly, CSC, which is known to increase viral replication in primary macrophages, was also found to induce CYP1 enzymes in HIV-infected primary macrophages. While mRNA levels of both CYP1A1 and CYP1B1 were elevated following CSC treatment, only CYP1B1 protein levels were increased in HIV-infected primary macrophages. In conclusion, these results suggest a possible association between oxidative stress, CYP1 expression, and viral replication in CSC-treated cells of myeloid lineage. This study warrants a closer examination of the role of CYP1B1 in smoking-mediated enhanced HIV replication