Increasing Maternal Blood Pressure with Ephedrine Increases Uterine Artery Blood Flow Velocity during Uterine Contraction

Background: During labor, ephedrine is widely used to prevent or to treat maternal arterial hypotension and restore uterine perfusion pressure to avoid intrapartum fetal asphyxia. However, the effects of ephedrine on uterine blood flow have not been studied during uterine contractions. The purpose of the study was to assess the effects of ephedrine on uterine artery velocities and resistance index using the Doppler technique during the active phase of labor.

Methods: Ten normotensive, healthy parturients with uncomplicated pregnancies at term received intravenous ephedrine during labor to increase mean arterial pressure up to a maximum of 20% above their baseline pressure. Peak systolic and end-diastolic Doppler flow velocities and resistance indices were measured in the uterine artery before and immediately after administration of bolus intravenous ephedrine and after ephedrine washout. Umbilical and fetal middle cerebral arterial resistance indices and fetal heart rate were also calculated.

Results: After ephedrine administration, mean arterial pressure increased by 17 +/- 4%. End-diastolic flow velocity in the uterine artery at peak amplitude of uterine contraction was restored to 74% of the value observed in the absence of contraction. The systolic velocity was totally restored, and the uterine resistance index was significantly decreased, compared with the values in the absence of contraction. Between uterine contractions, ephedrine induced similar but less marked effects. Fetal hemodynamic parameters were not altered by ephedrine administration.     

Selective alterations in the patterns of newly synthesized proteins by acetaminophen and its dimethylated analogues in primary cultures of mouse hepatocytes.

Alterations in protein synthesis following exposure to and recovery from hepatotoxic doses of acetaminophen (APAP) and its analogues, 3,5-dimethyl acetaminophen (3,5-DMA) and 2,6-dimethyl acetaminophen (2,6-DMA), were investigated in primary cultures of mouse hepatocytes. The rates of protein synthesis decreased within 4 hr after administration of 10 mM APAP and occurred after significant depletion of intracellular glutathione and covalent binding of APAP to proteins, but preceded the leakage of lactate dehydrogenase into the media. The inhibition of protein synthesis was reversible only if APAP exposure did not exceed 8 hr. Electrophoretic analysis of 35S-labeled proteins by one-dimensional SDS-PAGE revealed two consistent alterations in the patterns of newly synthesized proteins. First was a progressive diminution in the de novo synthesis of a protein migrating at approximately 58 kDa (p58). This was observed with APAP (10 mM) and 3,5-DMA (5 mM) but not with 2,6-DMA (10 mM). If exposure to APAP exceeded 8 hr, the biosynthesis of this protein was not only further decreased but was also no longer detectable during the recovery period. The second major alteration was an increase in the relative rate of biosynthesis of a 32-kDa protein (p32) following exposure and recovery from APAP and 3,5-DMA but not 2,6-DMA. Exposure to heme or arsenite induced the synthesis of a protein of similar molecular weight but did not result in the inhibition of p58 biosynthesis. The fact that the reactive metabolites of both APAP and 3,5-DMA, but not 2,6-DMA, possess oxidative properties suggests that the alterations in the synthesis of p32 and p58 may be related to an oxidative component induced by these compounds.     

Acute inflammatory response to cowpox virus infection of the chorioallantoic membrane of the chick embryo.

The chick embryo chorioallantoic membrane was used to study the acute inflammatory response in the absence of contributions from the immune system. In preliminary experiments, lesions of wild-type cowpox virus strain Brighton (CPV-BR) and a 38K gene deletion mutant of CPV-BR (CPV-BR.D1) were compared with vaccinia virus (strains WR and Copenhagen), fowlpox virus, laryngotracheitis virus, and infectious tenosynovitis virus, and were ranked for degree of induced inflammation. The maximal and minimal inflammatory responses were observed with CPV-BR.D1 and CPV-BR viruses, respectively. CPV-BR.D1 lacks a 38K gene which encodes an anti-inflammatory 38-kDa protein that has homology to SERPINs. The kinetics and character of the inflammatory response were examined further in the wild-type CPV-BR and mutant CPV-BR.D1 infections using cell counts, electron microscopy, and assays for inflammatory cell activation. CPV-BR virus infection rapidly spread through the ectoderm, uniformly infecting all cells with the production of large amounts of virions and viral-induced cytopathic effect, but evoking little or no inflammatory response until 144 hr p.i. The CPV-BR.D1 infection, on the other hand, was rapidly contained by a dexamethasone-sensitive inflammatory response mainly of activated heterophils which was advanced by 36 hr p.i. Both infections resulted in disseminated disease with similar numbers of liver lesions and only a slight difference in the LD50, with the CPV-BR.D1 values being higher than that for CPV-BR virus. In this model, the acute inflammatory response alone is unable to prevent disseminated disease and associated mortality.     

Spotlight on the role of hormonal factors in the emergence of autoreactive B-lymphocytes

Pathogenic autoimmunity requires a combination of inherited and acquired factors. In as much as hormones influence the sexual dimorphism of the immune system, it is possible that they can initiate or accelerate an autoimmune process, and contribute to gender-biased autoimmune disorders. Not only natural hormones, but also endocrine disruptors, such as environmental estrogens, may act in conjunction with other factors to override immune tolerance to self-antigens. In lupus, murine and human studies demonstrate that female sex hormones are implicated in disease pathogenesis. In the B cell compartment, both prolactin and estrogen are immunomodulators that affect maturation, selection and antibody secretion. Their impact may be based on their capacity to allow autoreactive B cells to escape the normal mechanisms of tolerance and to accumulate in sufficient numbers to cause clinically apparent disease. Both hormones lead to the survival and activation of autoreactive B cells, but they skew B cell maturation towards different directions, with prolactin inducing T cell-dependent autoreactive follicular B cells and estrogen eliciting T cell-independent autoreactive marginal zone B cells. Differential modulation of the cytokine milieu by hormones may also affect the development and activation of specific mature B cell subsets. This novel insight suggests that targeted manipulation of these pathways may represent a promising avenue in the treatment of lupus and other gender-biased autoimmune diseases.     

The Effect of Neonicotinoids Exposure on Oreochromis niloticus Histopathological Alterations and Genotoxicity

This study aimed to examine the side effects of selected neonicotinoids (Acetamiprid, Aceta, and Imidacloprid, Imid) on Oreochromis niloticus juveniles. The acute toxicity, Probit method, revealed an LC₅₀ of 195.81 and 150.76 ppm for Aceta/96 h and Imid/72 h respectively. The fish were divided into three groups that were exposed, for 21 days (n?=?5/replicate), to 1/10 of the LC₅₀ of either neonicotinoids, however, the third was an unexposed control group. Results of erythrocytic micronucleus (MN), and nuclear abnormalities (NA) showed that Aceta and Imid exposure caused a significant (p?<?0.05) increase in MN by?~?2.2 and?~?10 folds, respectively relative to control. NAs occurred at the order of kidney-shaped?>?budding?>?binucleated in Aceta, however, budding?>?binucleated?>?kidney-shaped was noticed in the Imid group. Histopathological changes in gills, liver, and muscles were observed significantly in both exposed groups with more severity in the Imid group. Collectively, Aceta and Imid have potential genotoxicity and histopathological alterations in O. niloticus.