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Actin remodeling is a critical regulator of mast cell secretion. In previous work, we have shown that dehydroleucodine and xanthatin, two natural α,β-unsaturated lactones, exhibit anti-inflammatory and mast cell stabilizing properties. Based on this background, this study aimed to determine whether the mast cell stabilizing action of these lactones is associated with changes in the actin cytoskeleton. Rat peritoneal mast cells were preincubated in the presence of dehydroleucodine or xanthatin before incubation with compound 48/80. Comparative studies with sodium cromoglycate and latrunculin B were also made. After treatments, different assays were performed on mast cell samples: β-hexosaminidase release, cell viability studies, quantification of mast cells and their state of degranulation by light microscopy, transmission electron microscopy, and actin staining for microscopy observation. Results showed that dehydroleucodine and xanthatin inhibited mast cell degranulation, evidenced by the inhibition of β-hexosaminidase release and decreased degranulated mast cell percentage. At the same time, both lactones altered the F-actin cytoskeleton in mast cells resulting, similarly to Latrunculin B, in a higher concentration of nuclear F-actin when activated by compound 48/80. For the first time, this study describes the biological properties of dehydroleucodine and xanthatin concerning to the rearrangement of actin filaments during stimulated exocytosis in mast cells. These data have important implications for developing new anti-inflammatory and mast cell stabilizing drugs and for designing new small molecules that may interact with the actin cytoskeleton., (© 2023 Wiley Periodicals LLC.)

The goal of the present work was to develop novel β-substituted-α-halomethyl acrylates from a methodology in an aqueous phase and to evaluate their bioactivity as potential inhibitors of mast cell activation. Eleven β-substituted-α-halomethyl acrylates were synthesized through a modified Horner-Wadsworth-Emmons reaction. Compound 48/80 and the calcium ionophore A23187 stimulated the release of β-hexosaminidase from mast cells. The effect induced by compound 48/80 was inhibited by compound 5 (320 µM) and compound 9 (160 and 320 µM) without causing cytotoxic effects. The effect induced by A23187 was inhibited by compound 5 (40, 80, 160, and 320 µM) without affecting cell viability. The inhibitory effects exhibited by compounds 5 and 9 were more potent than those of the reference compound sodium cromoglycate at the same concentrations. The biochemical results were consistent with the morphological findings obtained by light and transmission electron microscopy. This study reports, for the first time, that the new synthetic compounds methyl (Z)- 2-bromo-3-(furan-3-yl)acrylate (compound 5) and methyl (E)- 2-bromo-3-(3-bromophenyl)acrylate (compound 9) strongly inhibit mast cell degranulation, without affecting cell viability. The implications of these results are relevant as a basis for developing new anti-inflammatory and mast cell stabilizing drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

Introduction: The presentation, risk factors, and etiologies of white matter hyperintensities (WMH) in people exposed to repetitive head impacts are unknown. We examined the burden and distribution of WMH, and their association with years of play, age of first exposure, and clinical function in former American football players., Methods: A total of 149 former football players and 53 asymptomatic unexposed participants (all men, 45-74 years) completed fluid-attenuated inversion recovery magnetic resonance imaging, neuropsychological testing, and self-report neuropsychiatric measures. Lesion Segmentation Toolbox estimated WMH. Analyses were performed in the total sample and stratified by age 60., Results: In older but not younger participants, former football players had greater total, frontal, temporal, and parietal log-WMH compared to asymptomatic unexposed men. In older but not younger former football players, greater log-WMH was associated with younger age of first exposure to football and worse executive function., Discussion: In older former football players, WMH may have unique presentations, risk factors, and etiologies., Highlights: Older but not younger former football players had greater total, frontal, temporal, and parietal lobe white matter hyperintensities (WMH) compared to same-age asymptomatic unexposed men. Younger age of first exposure to football was associated with greater WMH in older but not younger former American football players. In former football players, greater WMH was associated with worse executive function and verbal memory., (© 2022 the Alzheimer's Association.)

Background: Patterns of cognitive impairment in former American football players are uncertain because objective neuropsychological data are lacking. This study characterized the neuropsychological test performance of former college and professional football players., Methods: One hundred seventy male former football players (n=111 professional, n=59 college; 45-74 years) completed a neuropsychological test battery. Raw scores were converted to T-scores using age, sex, and education-adjusted normative data. A T-score ≤ 35 defined impairment. A domain was impaired if 2+ scores fell in the impaired range except for the language and visuospatial domains due to the limited number of tests., Results: Most football players had subjective cognitive concerns. On testing, rates of impairments were greatest for memory (21.2% two tests impaired), especially for recall of unstructured (44.7%) versus structured verbal stimuli (18.8%); 51.8% had one test impaired. 7.1% evidenced impaired executive functions; however, 20.6% had impaired Trail Making Test B. 12.1% evidenced impairments in the attention, visual scanning, and psychomotor speed domain with frequent impairments on Trail Making Test A (18.8%). Other common impairments were on measures of language (i.e., Multilingual Naming Test [21.2%], Animal Fluency [17.1%]) and working memory (Number Span Backward [14.7%]). Impairments on our tasks of visuospatial functions were infrequent., Conclusions: In this sample of former football players (most of whom had subjective cognitive concerns), there were diffuse impairments on neuropsychological testing with verbal memory being the most frequently impaired domain., (© 2023. The Author(s).)

Helicobacter pylori infection is widespread worldwide, with more than a half of the world population infected. H. pylori antibiotic-resistant strains and non-compliance to therapy are the major causes of H. pylori eradication failure. The search for new therapies based on plant extracts is a scientific interest field. The present study was conducted to evaluate the effect in vitro of extra virgin olive oil (EVOO), hydroxytyrosol (HT), and oleuropein (Olp) against two H. pylori strains and the effect in vivo of the oral administration of EVOO on the gastric mucosa of BALB/c mice infected with this microorganism. The broth microdilution method assayed the antibacterial in vitro activity of EVOO, HT, and Olp against H. pylori strains. For in vivo studies, male BALB/c mice were infected orally with an H. pylori suspension every 72 h. Four groups were used: (1) Control, (2) H. pylori -infected (HP), (3) EVOO, and (4) HP + EVOO. Mice were sacrificed at 7, 15, and 30 days. The stomachs were removed and observed under a microscope. Scoring of the degree of erosion was determined. Samples were processed by histological techniques for light microscopy. Macroscopic analysis showed that the presence of small erosions increased, both in number and size, in the infected group. Animals infected and treated with EVOO exhibited the presence of fewer erosions, which decreased in number as the treatment progressed. The mucosa of the control and EVOO groups showed normal histological characteristics at the three times studied. The mucosa of animals infected with H. pylori showed disruptions of the lining epithelium, damage to gastric glands, and vasodilation. The mucosa of animals infected with H. pylori and treated with EVOO showed morphological characteristics similar to those of normal and EVOO mucosa. For the first time, the current study showed the effect in vitro and in vivo of EVOO and combined administration of HT and Olp against H. pylori using an animal model. Future studies are needed to establish the mechanism of EVOO's action at the gastric mucosa level to propose this product as a natural antimicrobial agent for the treatment of gastric H. pylori infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Arismendi Sosa, Mariani, Vega and Penissi.)

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine and validate clinical research diagnostic criteria (i.e., traumatic encephalopathy syndrome [TES]); examine repetitive head impact exposure, genetic, and other risk factors; and provide shared resources of anonymized data and biological samples to the research community. In this paper, we provide a detailed overview of the rationale, design, and methods for the DIAGNOSE CTE Research Project., Methods: The targeted sample and sample size was 240 male participants, ages 45-74, including 120 former professional football players, 60 former collegiate football players, and 60 asymptomatic participants without a history of head trauma or participation in organized contact sports. Participants were evaluated at one of four U.S. sites and underwent the following baseline procedures: neurological and neuropsychological examinations; tau and amyloid positron emission tomography; magnetic resonance imaging and spectroscopy; lumbar puncture; blood and saliva collection; and standardized self-report measures of neuropsychiatric, cognitive, and daily functioning. Study partners completed similar informant-report measures. Follow-up evaluations were intended to be in-person and at 3 years post-baseline. Multidisciplinary diagnostic consensus conferences are held, and the reliability and validity of TES diagnostic criteria are examined., Results: Participant enrollment and all baseline evaluations were completed in February 2020. Three-year follow-up evaluations began in October 2019. However, in-person evaluation ceased with the COVID-19 pandemic, and resumed as remote, 4-year follow-up evaluations (including telephone-, online-, and videoconference-based cognitive, neuropsychiatric, and neurologic examinations, as well as in-home blood draw) in February 2021., Conclusions: Findings from the DIAGNOSE CTE Research Project should facilitate detection and diagnosis of CTE during life, and thereby accelerate research on risk factors, mechanisms, epidemiology, treatment, and prevention of CTE., Trial Registration: NCT02798185., (© 2021. The Author(s).)

The aim of this study was to determine whether the lactones dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one, would be effective in an animal model of gastric ulcer induced by mast cell activation. Rats were divided into ten groups. Treatments were repeated for four days. The degree of gastric erosion was assessed with a scoring system and histological preparations. Gastric mast cell morphology was analyzed by histological procedures. Serum serotonin levels were determined as markers of mast cell activation. Statistical analyses were done using ANOVA and Tukey-Kramer test. We demonstrated that the repeated administration of compound 48/80 results in extensive mucosal lesions in the gastric mucosa and that such lesions occurred in association with mast cell degranulation and a significant increase of serum serotonin. We showed that these lesions were prevented by dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one and that this effect was similar to that obtained with sodium cromoglycate. In conclusion, the results of the present study indicate that the optimal gastric cytoprotective dose of dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5 H -furan-2-one is efficacious in an animal model of gastric ulcer induced by mast cell activation. Our findings suggest that these lactones could be valuable tools for designing novel therapeutic agents for digestive disorders associated with inappropriate mast cell activation.

Objective: To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE)., Methods: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES , April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298)., Results: Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features., Conclusions: New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available., (© 2021 American Academy of Neurology.)

Introduction: Mast cells are involved in not only inducing, but also maintaining neurogenic inflammation and neuropathic pain. In previous work, we have demonstrated that dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit rat peritoneal and human LAD2 mast cell degranulation induced by compound 48/80 and calcium ionophore A23187. However, the effect of these molecules on neuropeptide-induced mast cell activation has not been studied so far., Objective: The aim of this study was to determine whether dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one inhibit neuropeptide-induced mast cell activation., Methods: This work is based on in vitro simulation of a neurogenic inflammation scenario involving neuropeptides and mast cells, to subsequently analyze potential therapeutic strategies for neuropathic pain., Results: Neuromedin-N did not stimulate mast cell serotonin release but substance P and neurotensin did induce serotonin release from peritoneal mast cells in a dose-dependent manner. Mast cell serotonin release induced by substance P and neurotensin was inhibited by dehydroleucodine and xanthatin, but not by 3-benzyloxymethyl-5H-furan-2-one. The inhibitory potency of dehydroleucodine and xanthatin was higher than that obtained with the reference compounds, ketotifen and sodium chromoglycate, when mast cells were preincubated with dehydroleucodine before substance P incubation, and with dehydroleucodine or xanthatin before neurotensin incubation., Conclusions: These results are the first strong evidence supporting the hypothesis that dehydroleucodine and xanthatin inhibit substance P- and neurotensin-induced serotonin release from rat peritoneal mast cells. Our findings suggest, additionally, that these α,β-unsaturated lactones could be of value in future pharmacological research related to inappropriate mast cell activation conditions such as neurogenic inflammation and neuropathic pain.

The UV/H2O2 process was applied to the treatment of different mixtures of herbicides in water. Glyphosate, the herbicide most used in the world, was mixed with other hormonal herbicides with residual activity as 2,4-D and dicamba. The main goals of the study were to develop a kinetic model for interpreting the simultaneous oxidation of two mixtures (glyphosate plus 2,4-D and glyphosate plus dicamba). The model is based on a complete reaction mechanism, which comprises hydrogen peroxide photolysis and decomposition of both herbicides in each mixture studied. It takes into account the effect of non-uniform distribution of the local rate of absorbed photons. Good agreement of experimental data and the model is achieved in spite of differences in the reactivity between glyphosate and 2,4-D (or dicamba). Toxicity assays (employing Vibrio fischeri) were also performed, indicating that the toxicity of the mixture of glyphosate and 2,4-D was significantly reduced after the treatment.

The aim of this study was to determine whether hydroxytyrosol and oleuropein, the major phenols found in olives and olive oil, inhibit mast cell activation induced by immune and non-immune pathways. Purified peritoneal mast cells were preincubated in the presence of test compounds (hydroxytyrosol or oleuropein), before incubation with concanavalin A, compound 48/80 or calcium ionophore A23187. Dose-response and time-dependence studies were carried out. Comparative studies with sodium cromoglycate, a classical mast cell stabilizer, were also made. After incubation the supernatants and pellets were used to determine the β-hexosaminidase content by colorimetric reaction. The percentage of β-hexosaminidase release in each tube was calculated and taken as a measure of mast cell activation. Other samples of cell pellets were used for cell viability studies by the trypan blue dye exclusion test, or fixed for light and electron microscopy. Biochemical and morphological findings of the present study showed for the first time that hydroxytyrosol and oleuropein inhibit mast cell degranulation induced by both immune and non-immune pathways. These results suggest that olive phenols, particularly hydroxytyrosol and oleuropein, may provide insights into the development of useful tools for the prevention and treatment of mast cell-mediated disorders., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

The H(2)O(2)/UVC process was applied to the photodegradation of a commercial formulation of glyphosate in water. Two organisms (Vibrio fischeri bacteria and Rhinella arenarum tadpoles) were used to investigate the toxicity of glyphosate in samples M(1,) M(2), and M(3) following different photodegradation reaction times (120, 240 and 360 min, respectively) that had differing amounts of residual H(2)O(2). Subsamples of M(1), M(2), and M(3) were then used to create samples M(1,E), M(2,E) and M(3,E) in which the H(2)O(2) had been removed. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in tadpoles to determine possible sub-lethal effects. In V. fischeri, M(1,E), which was collected early in the photodegradation process, caused 52% inhibition, while M(3,E), which was collected at the end of the photodegradation process, caused only 17% inhibition. Survival of tadpoles was 100% in samples M(2), M(3), and in M(1,E), M(2,E) and M(3,E). The lowest percentages of enzymatic inhibition were observed in samples without removal of H(2)O(2): 13.96% (AChE) and 16% (BChE) for M(2), and 24.12% (AChE) and 13.83% (BChE) for M(3). These results show the efficiency of the H(2)O(2)/UVC process in reducing the toxicity of water or wastewater polluted by commercial formulations of glyphosate. According to the ecotoxicity assays, the conditions corresponding to M(2) (11 ± 1 mg a.e. L(-1) glyphosate and 11 ± 1 mg L(-1) H(2)O(2)) could be used as a final point for glyphosate treatment with the H(2)O(2)/UV process.

The aim of the present study was to determine whether dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit the activation of human leukemic LAD2 mast cells induced by compound 48/80 or the calcium ionophore A23187. LAD2 cells were preincubated in the presence of test drugs and then challenged with the secretagogues. This study provides the first evidence in favor of the view that dehydroleucodine and xanthatin inhibit the degranulation of LAD2 cells, thus acting as human mast cell stabilizers. These molecules could be effective in the treatment of human diseases associated with inappropriate mast cell activation.

The degradation reaction of a simple mixture of pollutants (dichloroacetic acid + formic acid) employing H2O2 and UVC radiation (253.7 nm) has been studied in a well-mixed reactor which operates inside a recycling system. The aim of this work is to develop a systematic methodology for treating degradation of mixtures of pollutants, starting from a rather manageable system to more complex aggregates. In this contribution, the effects of different variables such as hydrogen peroxide/pollutant mixture initial concentration ratio, pH and incident radiation at the reactor wall were studied. The results show that the best degrading conditions are: pH = 3.5 and hydrogen peroxide concentrations from 3.9 to 11.8 mM (134-400 mg/L), for initial concentrations of 1.10 and 0.39 mM for formic acid and dichoroacetic acid respectively (50 mg/L for both pollutants). The influence of the incident radiation at the reactor wall on the degradation rates of the mixture is significant. In addition to this, it has been shown that in the employed aqueous solution no stable reaction intermediates are formed. On this basis, a complete reaction scheme for the mixture is proposed that is suitable for a reaction kinetics mathematical modeling of the mixture and further studies of increasing complexity.

The present study was designed to examine the effects of a sesquiterpene lactone isolated from Artemisia douglasiana Besser (dehydroleucodine), a xanthanolide sesquiterpene isolated from Xanthium cavanillesii Schouw (xanthatin) and a semisynthetic butenolide (3-benzyloxymethyl-5H-furan-2-one) on mast cell degranulation induced by compound 48/80. Peritoneal mast cells from male adult Sprague-Dawley rats were purified in Percoll, preincubated in the presence of test lactones (dehydroleucodine, xanthatin or 3-benzyloxymethyl-5H-furan-2-one) and then challenged with the mast cell activator compound 48/80 (10 microg/ml). Concentration-response and kinetic studies of mast cell serotonin release evoked by compound 48/80, evaluation of mast cell viability and morphology by light and electron microscopy, and comparative studies using ketotifen and sodium chromoglycate were carried out. Serotonin release studies, carried out together with morphological studies, showed the effectiveness of the above lactones to stabilize mast cells. The comparative study with ketotifen and sodium chromoglycate, well known mast cell stabilizers, showed the following order of potency dehydroleucodine=xanthatin>3-benzyloxymethyl-5H-furan-2-one> or =ketotifen/sodium chromoglycate to inhibit mast cell serotonin release induced by compound 48/80. The present study provides the first strong evidence in favour of the hypothesis that dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit compound 48/80-induced serotonin release from peritoneal mast cells, acting thus as mast cell stabilizers. Our findings may provide an insight into the design of novel pharmacological agents which may be used to regulate the mast cell response.

Mammalian tissues express both cation-dependent (CD-MPR) and cation-independent (CI-MPR) mannose-6-phosphate receptors, which mediate the targeting of acid hydrolases to lysosomes. The coexistence of the two receptors in all cell types and tissues is still poorly understood. To determine whether these receptors might play a role in maturation, we studied their expression and binding properties in rat liver during perinatal development. CI-MPR expression decreases progressively from 18-day fetuses to adults, whereas the CD-MPR showed a transient decrease in newborn and at the 5th day after birth. Immunostaining of the tissues showed that both receptors localize to hepatocytes at all the ages and, additionally, the CD-MPR was reactive in megakaryocytes at early stages. Binding assays showed differences in the B(max) and K(D) values between the ages studied. These results demonstrate that both receptors change differentially during perinatal development, suggesting that they play distinct roles during organ maturation.

Certain heat shock proteins are regulated by steroid hormones and are associated with oestrogen receptor function in reproductive tissues, indicating that these proteins have a role during implantation, decidualization and placentation. In the present study, the expression of hsp25, hsp70 and oestrogen receptor alpha were examined by immunohistochemistry in oviducts from rats during neonatal development, the oestrous cycle and during early pregnancy. Oestrogen receptor alpha was the first protein observed in the neonatal oviduct, and its expression preceded that of hsp70 and hsp25. Although these heat shock proteins have been associated with the oestrogen receptor, this study showed that during early development of the oviduct, the receptor protein was not associated with the concomitant expression of hsp25 and hsp70. However, these heat shock proteins were expressed when oviductal cells became differentiated. In the adult oviduct, hsp70 was more abundant than hsp25, moreover, there were no significant modifications in expression of hsp25 during the oestrous cycle. In contrast, the expression of hsp70 was significantly higher in epithelial cells during dioestrus, when the maximum amount of oestrogen receptor alpha was also observed. Therefore, the present study shows that hsp70, but not hsp25, is an oviductal protein modulated by the oestrous cycle and that it is a protein marker for specific phases of the oestrous cycle. In addition, hsp70 was more responsive to the hormonal changes in the infundibulum and ampullar regions of the oviduct. During early pregnancy, hsp25 expression was downregulated (unlike in the endometrium), whereas hsp70 was relatively abundant in the oviduct. hsp70 was observed in all functional segments of the oviduct during pregnancy, indicating that in the oviduct, this protein is modulated by oestrogens and progesterone and possibly by other pregnancy-related hormones.

Aim of this article is an up-dating of the state of the art of color Doppler US in the assessment of intrahepatic vascularization. Recent reports are reviewed, based on already acquired certainties to better the knowledge of the physiology and pathophysiology of hepatic circulation to investigate new clinical applications of color Doppler US.

Adrenal medulla together with the sympathetic nervous system constitute an anatomo functional unit. Both tissues derive from precursor cells which originate from the neural crest and later differentiate during migration into sympathetic neurons or chromaffin cells. Biosynthesis enzymes of catecholamines such as DBH (dopamine beta hydroxylase) and PNMT (phenylethanol amine-N-methyl transferase) as well as the neurotransmitter serotonin , can be detected by immunohistochemical techniques from 15 to 20 prenatal days. Cells migrating along the dorsal aorta could be observed at 15 prenatal days. From day 16 on, three distinct cellular groups could be distinguished according to the intensity of the immunoreactivity: chromaffin, paraganglion and sympathetic ganglion cells. From day 18, chromaffin cells immunostained as DBH' PNMT+ or DBH+ PNMT could be detected differentiating into what would be adrenergic or noradrenergic cells, respectively Progenitor cells migrating from the neural crest to the adrenal cortical blastema reach a micro-environment where glucocorticoids could possibly influence gene expression for PNMT in some of these undifferentiated cells, causing adrenaline synthesis. Serotonin(5HT) immunoreactivity is localized from 17 prenatal days in several groups of the paraganglionic cells where they could be a modulator for chromaffin differentiation.

Objective: Our objective was to investigate the possible restoring action of magnesium on vascular sensitivity to angiotensin II in pregnancy., Study Design: We studied intraplatelet free calcium and the pressor response to angiotensin II in 10 primigravid women (28 to 32 weeks' gestation) at risk for pregnancy induced hypertension on the basis of altered uteroplacental blood velocity waveforms at 20 weeks' gestation, before and after the infusion of 1 gm of magnesium pyrrolidone carboxylate. After the effective pressor dose was achieved or a maximum of 32 ng/kg per minute was reached, we infused 1 gm magnesium pyrrolidone carboxylate and repeated the test. Intraplatelet free calcium was measured by means of fluorescent probes at the beginning and the end of both tests., Results: Six women were classified as refractory to angiotensin II and four as sensitive (effective pressor dose < 10 ng/kg per minute). After magnesium pyrrolidone carboxylate infusion, the four sensitive women became refractory and the effective pressor dose was significantly enhanced to 32 in all six refractory women. Intracellular free calcium increased significantly during the first angiotensin II infusion, whereas after magnesium pyrrolidone carboxylate administration it did not change significantly., Conclusions: Magnesium pyrrolidone carboxylate enhances the vascular refractoriness and intracellular free calcium mediates the pressor response to angiotensin II in pregnancy.