Autacoid interactions in the regulation of blood flow in the human placenta

1. Interactions between autacoids may play important roles in the regulation of blood flow in the foetal placenta. In order to investigate this aspect of placental haemodynamics, human normal-term placentae were perfused in vitro and the responses of the foetal vessels to various combinations of vasoactive agents were determined. 2. Vasoconstriction responses to 5-hydroxytryptamine (5-HT) were potentiated in the presence of endothelin-1 (ET-1), the thromboxane A2-mimetic U46619 and a nitric oxide synthase inhibitor, N-nitro-L-arginine (NOLA), but not in the presence of angiotensin II. 3. N-Nitro-L-arginine caused vasoconstriction of the perfused placenta and indomethacin attenuated this effect and blocked the potentiation of the 5-HT response by NOLA. 4. Indomethacin did not affect ET-1-induced pressure increases and infusion of U46619 had no effect on release of ET-like immunoreactivity into the foetal placental circulation. 5. The present study provides evidence of interactions between several autacoids in human perfused placentae in vitro. These interactions may play important roles in foetal placental haemodynamics in normal or pathological situations.     

Prediction of early-onset esotropia from components of the infantile squint syndrome

PURPOSE: To examine the association between components of the infantile squint syndrome (ISS) and age of onset of esotropia among subjects in the Cooperative Amblyopia Classification Study (CACS). METHODS: Fifty subjects were classified retrospectively as having early-onset esotropia (EOE) and 150 subjects were classified as having late-onset esotropia (EOE), depending on whether symptoms of (or treatment for) strabismus occurred before the first birthday or between the first and ninth birthdays, respectively. The authors compared the degree to which latent nystagmus (LN), dissociated vertical deviation (DVD), monocular asymmetry of optokinetic nystagmus (MOKN), monocular asymmetry of smooth pursuit (MSP), and perceived monocular speed bias (MSB) predicted EOE. RESULTS: Slow-phase velocity of MOKN and MSP were faster in response to nasal than to temporal target motion. In contrast, MSB revealed that targets of equal velocity were perceived as moving faster temporally than nasally. The authors evaluated MOKN, MSP, and MSB as dichotomous and as continuous predictors. Dichotomous analysis showed significant associations between DVD and asymmetries of MOKN in the preferred eye of subjects with EOE. Univariate logistic regression models, based on DVD and LN as well as on continuous measures of MOKN, MSP, and MSB, revealed predictive power for all ISS components except LN. In the preferred eye, MSP asymmetry was the strongest single predictor of EOE; multivariate analysis revealed that prediction of EOE improved with the inclusion of DVD. CONCLUSIONS: Multivariate analysis indicated that dichotomous measures of DVD and continuous measures of MSP were independent predictors of EOE in a population of 8- to 40-year-old subjects with strabismus. In the preferred eye, MOKN asymmetry was predictive of EOE in the absence of information about MSP. Predictive values of all ISS components depended heavily on the baseline prevalence of EOE in the target population.     

Platelet alpha-granules

Platelets contain a vast number of biologically active molecules within cytoplasmic granules which are classified according to their respective distinct ultrastructures, densities and content. The alpha-granule is a unique secretory organelle in that it exhibits further compartmentalization and acquires its protein content via two distinct mechanisms: (1) biosynthesis predominantly at the megakaryocyte (MK) level (with some vestigial platelet synthesis) (e.g. platelet factor 4) and (2) endocytosis and pinocytosis at both the MK and circulating platelet levels (e.g. fibrinogen (Fg) and IgG). The currently known list of alpha-granular proteins continues to enlarge and includes many adhesive proteins (e.g. Fg, von Willebrand factor (vWf) and thrombospodin (TSP)), plasma proteins (e.g. IgG and albumin), cellular mitogens (e.g. platelet derived growth factor and TGF beta), coagulation factors (e.g. factor V) and protease inhibitors (e.g. alpha 2-macroglobulin and alpha 2-antiplasmin). More recently the inner lining of the alpha-granule unit membrane has been demonstrated to contain a number of physiologically important receptors including glycoprotein IIb/IIIa (alpha IIb beta 3) and P-selectin. The alpha-granules originate from small precursor granules which can be observed budding from the trans-Golgi network within the platelet precursor cell the MK. During MK maturation the alpha-granules become very prominent and are ultimately packaged into platelets during thrombopoiesis. The alpha-granular contents are destined for release during platelet activation at sites of vessel wall injury and thus play an important role in haemostasis, inflammation, ultimate wound repair and in the pathogenesis of atherosclerosis.