Venezuelan equine encephalitis (VEE) is an emerging infectious disease in Latin America. Outbreaks have been recorded for decades in countries with enzootic circulation, and the recent implementation of surveillance systems has allowed the detection of additional human cases in countries and areas with previously unknown VEE activity. Clinically, VEE is indistinguishable from dengue and other arboviral diseases and confirmatory diagnosis requires the use of specialized laboratory tests that are difficult to afford in resource-limited regions. Thus, the disease burden of endemic VEE in developing countries remains largely unknown, but recent surveillance suggests that it may represent up to 10% of the dengue burden in neotropical cities, or tens-of-thousands of cases per year throughout Latin America. The potential emergence of epizootic viruses from enzootic progenitors further highlights the need to strengthen surveillance activities, identify mosquito vectors and reservoirs and develop effective strategies to control the disease. In this article, we provide an overview of the current status of endemic VEE that results from spillover of the enzootic cycles, and we discuss public health measures for disease control as well as future avenues for VEE research.
Although prostaglandin E 2 (PGE 2 ) has been identified as a central mediator of the cervical ripening process, the mechanisms responsible for PGE 2 ripening are still poorly understood, partly because of the lack of information concerning the precise cellular localization and regulation of PGE 2 (EP) receptors in the cervix. To provide new insights into the mechanisms of cervical ripening, we used indirect immunofluorescence to localize cervical EP receptor protein expression in ovariectomized ewes and examined the effect of administration of progesterone or estradiol. EP receptors were widely distributed in cervical blood vessels, epithelium of the cervical canal, circular and longitudinal muscles, and stroma. Estradiol replacement decreased EP 1 and EP 3 receptor protein in blood vessel media (by 23 and 31% respectively, P < 0.05) and decreased EP 1 receptor protein expression in the longitudinal muscle layer (by 27%, P < 0.05). Stromal EP 1 and EP 3 receptor protein expression was also reduced by estradiol (by 29 and 20% respectively, P < 0.05). Progesterone replacement had no significant effect on EP receptor protein expression. The arterial changes would favor PGE 2 -induced vasodilatation, subsequent edema and leukocyte infiltration during the cervical ripening process whereas the muscular alterations would facilitate smooth muscle relaxation and cervical dilatation. Furthermore, estradiol provoked perinuclear localization of EP 3 receptor protein in the longitudinal muscle layer. This latter result suggests that cellular EP receptor localization is regulated by estradiol and that PGE 2 may also control smooth muscle contraction and regulate ovine cervical dilatation in an intracrine manner via EP 3 receptors.
ABSTRACT:The fetal lung produces and metabolizes prostaglandin (PG) E 2. In vitro PGE 2 induces surfactant production via E prostaglandin (EP) 1 and cyclic adenosine monophosphate (cAMP)-coupled EP (EP 2 and EP 4 ) receptors. Glucocorticoids alter PG function and increase lung function in preterm neonates. We hypothesized that fetal exposure to maternally administered betamethasone (M) enhances fetal lung EP 1 and cAMP-coupled EP receptor expression. Pregnant baboons were injected intramuscularly (i.m.) with either M (n ϭ 7) or saline [control (CTR); n ϭ 8] at 0.7 gestation. Fetal lungs were removed at cesarean section 48 h after the first injection. We determined mRNA levels, protein localization and abundance for all four PGE 2 receptors by real-time polymerase chain reaction (PCR), immunohistochemistry, and Western blot. EP receptors were widely distributed in bronchiolar epithelium, bronchiolar smooth muscle, and endothelium and media of blood vessels, but not alveoli. Compared with CTR, M exposure resulted in a twofold EP 2 mRNA decrease (p Ͻ 0.05) in male fetuses only. EP 1 , EP 3 , and EP 4 receptor mRNA levels were unaffected. Western blot analysis showed no alteration in EP receptor protein expression. In summary, this is the first demonstration of the four EP receptors in fetal lung. The only change after 48-h M exposure was a gender-specific decrease in EP 2 receptor mRNA. PGE 2 is produced (5,6) and metabolized in the fetal lung (6,7). PGE 2 tranduces its signal via seven-transmembrane domain, G protein-coupled receptors, called EP receptors (8). The EP receptor family has been further classified into four subtypes, EP 1 , EP 2 , EP 3 , and EP 4 (9), differing in their structure, ligand-binding affinities, and signal transduction pathways (8). EP 1 and EP 3 receptors, linked to the Ca 2ϩ / phospholipase C pathway, cause smooth muscle contraction (8), whereas EP 2 and EP 4 receptors, coupled to the cAMP/ adenylate cyclase pathway, induce relaxation of smooth muscle (8). In the lung, PGE 2 functions as a bronchiolar tone modulator. EP 1 and EP 3 receptors mediate bronchoconstriction indirectly through activation of neuronal pathways (10), whereas bronchodilatation results from direct activation of EP 2 receptors on airway smooth muscles (10 -12). Furthermore, PGE 2 induces SP-A synthesis by human fetal lung explants via the cAMP pathway (13) and phosphatidylcholine secretion via EP 1 receptor in rat cultured alveolar type II cells (14).The first aim of this study was to evaluate the presence and determine cellular localization of EP receptor expression in the fetal baboon lung. Glucocorticoids have been shown to alter PG synthesis and metabolism (15,16); however, no data exist relating to potential alterations in PG receptor-mediated function. To address potential effects of glucocorticoid on PG receptors, we hypothesized that M enhances EP 1 and cAMPcoupled EP (i.e. EP 2 and EP 4 ) receptor expression in the fetal lung. Randomized trials in pregnant women have demonstrated that the major benefit ...
ObjectiveTo examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth.MethodsPregnant rats were exposed to a severe hypoxia (9.5%–10% O2) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O2) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student’s t test and simple regression were used for statistical analysis.ResultsAs the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count.ConclusionIn a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.
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