scholarly journals Extracellular and Intracellular Magnesium Deficiency Found in Pregnant Women with Preeclampsia and Gestational Diabetes Is Associated with Overexpression of Notch Proteins, Cytokines, p53, NF-kB and Proto-Oncogenes: Potential Importance in Growth Retardation, Stillbirths, Fetal Mutations and Increased Cardiovascular Risks and Stroke with Advancing Age in Pregnant Women

Hearts ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 139-148
Author(s):  
Burton M. Altura ◽  
Anthony Carella ◽  
Nilank C. Shah ◽  
Gatha J. Shah ◽  
Lawrence M. Resnick ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Blood Vessels ◽  
Magnesium Deficiency ◽  
Notch Pathway ◽  
Contractile Force ◽  
Cardiovascular Risks ◽  
Intracellular Magnesium ◽  
Mg Deficiency ◽  
New Findings

In 1983, three of us reported in “Science” that umbilical-placental arteries and veins, obtained from normal pregnant women at term delivery, when exposed in vitro to low concentrations of Mg2+ went into vasospasm; the lower the Mg2+, the greater the contractile force developed. These blood vessels also demonstrated amplified contractile force development when challenged with circulating amines and peptides (e.g., norepinephrine, 5-HT, angiotensin II, etc.). We suggested that severe Mg deficiency during pregnancy could in part be responsible for spontaneous abortions, loss of fetuses, stillbirths, and developmental alterations in infants. Using short-term dietary Mg deficient animals, we have noted a great many molecular and biochemical alterations in ventricular, atrial and somatic vascular smooth muscle alterations including DNA methylation and histone changes leading us to speculate that Mg deficiency may represent a genotoxin promoting mutations and causing epigenetic changes. Over the last 35 years, we have new data on severely preeclamptic and gestational diabetic pregnant women that gives credence to our original hypothesis and demonstrates that recently- discovered developmental proteins, originally found 100 years ago in Drosophila fruit flies termed the “Notch pathway”, due to effects on its wings, appears to be important in development of the umbilical-placental blood vessels in pregnant women. Along with the developmental molecule, p53, these Notch proteins clearly alter the behavior of the umbilical-placental vessels. We believe these new findings probably help to explain many of the genetic-toxicity effects seen in women later in life who develop strokes and cardiovascular diseases. Notch alterations could also play an important role in babies born with cardiac defects.

scholarly journals On the origin of the increased tissue iron content in graded magnesium deficiency states in the rat

1997 ◽  
Vol 77 (3) ◽  
pp. 475-490 ◽  
Author(s):  
Klaus Schumann ◽  
Annette Lebeau ◽  
Ursula Gresser ◽  
Theodor Gunther ◽  
Jürgen Vormann
Keyword(s):  
Haemolytic Anaemia ◽  
Rapid Growth ◽  
Magnesium Deficiency ◽  
Erythropoietic Activity ◽  
Mg Deficiency ◽  
Adequate Diet ◽  
Fe Content ◽  
High Degree

To investigate the mechanism of tissue Fe accumulation in graded Mg deficiency rats were fed on diets of different Mg contents (70, 110, 208, 330, and 850 mg Mg/kg) for 10, 20, and 30 d during rapid growth. There was no significant impact of Mg deficiency or high luminal Mg concentrations on intestinal59Fe transferin vitroorin vivo. Plasma Mg concentrations and body weight started to decrease after 10 d. Significant haemolytic anaemia was observed after 20 d with siderosis in liver and spleen developing in parallel. Anaemia showed no features of Fe deficiency or infiammation. Comparison between the 70 mg Mg/kg group and animals that received the same quantity of a Mg-adequate diet (850 mg Mg/kg) permitted estimation of quantities of Fe liberated by haemolysis and the increased Fe content in liver and spleen. Both variables showed a high degree of correlation, indicating that the excess of liberated haemoglobin Fe was stored in the tissue. The erythropoietic activity was high during rapid growth, i.e. at days 10 and 20 and decreased significantly after 30 d in all except the most Mg-deficient groups. However, haemolytic anaemia developed because even the high erythropoietic activity in the 70 and 110 mg Mg/kg groups was not sutlicient to recycle all haemoglobin Fe liberated by haemolysis. After 30 d of Mg-deficient feeding the erythrocyte Mg content had decreased to 40% of control values. According to the literature Mg-deficient erythrocytes have a decreased survival time which is likely to be the cause of the observed haemolysis.

Thrombotic microangiopathy: A role for magnesium?

2012 ◽  
Vol 107 (03) ◽  
pp. 399-408 ◽  
Author(s):  
Evi V. T. Nagler ◽  
Raymond Vanholder ◽  
Steven Van Laecke
Keyword(s):  
Thrombotic Microangiopathy ◽  
Magnesium Deficiency ◽  
Treatment Modalities ◽  
Magnesium Supplementation ◽  
Intracellular Magnesium ◽  
Endothelial Homeostasis ◽  
Dose Dependent

SummaryDespite advances in more recent years, the pathophysiology and especially treatment modalities of thrombotic microangiopathy (TMA) largely remain enigmatic. Disruption of endothelial homeostasis plays an essential role in TMA. Considering the proven causal association between magnesium and both endothelial function and platelet aggreg-ability, we speculate that a magnesium deficit could influence the course of TMA and the related haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. A predisposition towards TMA is seen in many conditions with both extracellular and intracellular magnesium deficiency. We propose a rationale for magnesium supplementation in TMA, in analogy with its evidence-based therapeutic application in pre-eclampsia and suggest, based on theoretical grounds, that it might attenuate the development of TMA, minimise its severity and prevent its recurrence. This is based on several lines of evidence from both in vitro and in vivo data showing dose-dependent effects of magnesium supplementation on nitric oxide production, platelet ag-gregability and inflammation. Our hypothesis, which is further amenable to assessment in animal models before therapeutic applications in humans are implemented, could be explored both in vitro and in vivo to decipher the potential role of magnesium deficit in TMA and of the effects of its supplementation.

Effects of Mg deficiency and parathyroidectomy on gastrointestinal Ca transport in the rat

1969 ◽  
Vol 217 (6) ◽  
pp. 1608-1613 ◽  
Author(s):  
Richard M. Morehead ◽  
David M. Kessner
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Transport ◽  
Magnesium Deficiency ◽  
Intestinal Transport ◽  
Parathyroid Glands ◽  
Mg Deficiency ◽  
Enhancing Effect ◽  
Ca Transport ◽  
Everted Gut Sac

An open-ended, everted gut-sac technique was used to measure in vitro duodenal transfer of calcium in magnesium-deficient and pair-fed control animals with and without parathyroid glands. In contrast to previous studies employing the closed gut-sac technique in calcium-deprived animals, we were unable to demonstrate an effect of parathyroidectomy on the in vitro transport of calcium across the duodenum. Magnesium deficiency resulted in enhanced intestinal transport of calcium. These data confirm our previous studies and demonstrate that this effect of magnesium deficiency is linear over 2 hr of incubation. This enhancing effect of magnesium deficiency on gastrointestinal calcium transport was blocked by parathyroidectomy. The results of this study are consistent with the hypothesis that magnesium deficiency increases calcium transfer of the isolated everted gut-sac of rats by stimulating the secretion of parathyroid hormone.

scholarly journals The Hemolytic Anemia of Magnesium Deficiency in Adult Rats

Blood ◽  
1973 ◽  
Vol 41 (3) ◽  
pp. 451-459 ◽  
Author(s):  
Sergio Piomelli ◽  
Valerie Jansen ◽  
Joseph Dancis
Keyword(s):  
Structural Defect ◽  
Energy Production ◽  
Magnesium Deficiency ◽  
Osmotic Fragility ◽  
Deficient Diet ◽  
Adult Rats ◽  
In Vitro Synthesis ◽  
Mg Deficiency ◽  
Extrinsic Defect

Abstract The administration of a Mg-deficient diet to adult rats for 4-5 wk causes anemia. The RBC are slightly smaller and flatter, and have a reduced hemoglobin component and a decreased osmotic fragility. 51Cr survival time is shortened when the affected cells are infused into normal adult rats. In vitro synthesis of heme and globin, as measured with 14C-glycine was the same as in control rats with "reticulocytosis-rich" anemia produced by bleeding or immunologically. The activity of a series of enzymes associated with energy production also failed to yield findings specific for Mg deficiency. It is suggested that the anemia of Mg deficiency is hemolytic and results from the combination of a reversible extrinsic defect and of an irreversible structural defect in the RBC.

Insights into the biochemical and functional characterization of sortase E transpeptidase of Corynebacterium glutamicum

2019 ◽  
Vol 476 (24) ◽  
pp. 3835-3847 ◽  
Author(s):  
Aliyath Susmitha ◽  
Kesavan Madhavan Nampoothiri ◽  
Harsha Bajaj
Keyword(s):  
Protein Engineering ◽  
Cell Attachment ◽  
Functional Characterization ◽  
Protein Structures ◽  
Structural Similarity ◽  
Surface Proteins ◽  
Sortase A ◽  
Peptide Cleavage ◽  
New Findings

Most Gram-positive bacteria contain a membrane-bound transpeptidase known as sortase which covalently incorporates the surface proteins on to the cell wall. The sortase-displayed protein structures are involved in cell attachment, nutrient uptake and aerial hyphae formation. Among the six classes of sortase (A–F), sortase A of S. aureus is the well-characterized housekeeping enzyme considered as an ideal drug target and a valuable biochemical reagent for protein engineering. Similar to SrtA, class E sortase in GC rich bacteria plays a housekeeping role which is not studied extensively. However, C. glutamicum ATCC 13032, an industrially important organism known for amino acid production, carries a single putative sortase (NCgl2838) gene but neither in vitro peptide cleavage activity nor biochemical characterizations have been investigated. Here, we identified that the gene is having a sortase activity and analyzed its structural similarity with Cd-SrtF. The purified enzyme showed a greater affinity toward LAXTG substrate with a calculated KM of 12 ± 1 µM, one of the highest affinities reported for this class of enzyme. Moreover, site-directed mutation studies were carried to ascertain the structure functional relationship of Cg-SrtE and all these are new findings which will enable us to perceive exciting protein engineering applications with this class of enzyme from a non-pathogenic microbe.

Persistence of Fibrinolytic Activity in Fragments of Human Veins Cultured in Vitro

1970 ◽  
Vol 24 (01/02) ◽  
pp. 043-047 ◽  
Author(s):  
M Pandolfi
Keyword(s):  
Blood Vessels ◽  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Vasa Vasorum ◽  
Adult Human ◽  
Slide Technique

SummaryExplants from 5 adult human veins were cultured in a fibrinolytically inactive medium for 3 weeks and assayed for the presence of plasminogen activator by the fibrin slide technique. The explants from 3 veins showed fibrinolytic activity confined to their vasa vasorum for the whole duration of the culture; no decrease of activity was seen. The finding suggests that small blood vessels are able to synthesize plasminogen activator.

EKSTRAK KULIT BUAH MANGGIS (Garcinia Mangostana L.) SEBAGAI OBAT ANTI DIARE

2019 ◽  
Vol 2 (1) ◽  
pp. 9-13
Author(s):  
Zaim Anshari ◽  
Chrismis Novalinda Ginting ◽  
Linda Chiuman ◽  
Yuliani Mardiati Lubis
Keyword(s):  
Blood Vessels ◽  
Smooth Muscles ◽  
Latin Square ◽  
Ethanol Extract ◽  
Garcinia Mangostana ◽  
Pharmacology And Toxicology ◽  
The Difference ◽  
North Sumatra ◽  
Papaverine Hydrochloride

This study aims to determine whether mangosteen rind extract (in the form of ethanol extract/EE) can be used as an anti-diarrhea drug after compared with other anti-diarrhea substances in three experimental groups. This research is an in vitro experimental study using adult male guinea pigs weighing 400-600 gr through the standard method of Magnus with the Latin square controlled experiment design. The study was conducted at the Pharmacology and Toxicology Laboratory of the Faculty of Pharmacy, University of North Sumatra. The results showed that the contraction of ileum in Ach with Atp + Ach compared the difference in contraction of ileum Ach with EE + Ach showed the difference in difference between the two contractions of the ileum was significant, the contraction of ileum in His with Dip + His compared indifference in contraction of ileum His with EE + His showed a difference indifference. the two ileal contractions are significant, the ileal contraction in the bar with Papa + Bar compared to the difference between the ileum bar contraction with EE + Bar shows no difference in the difference between the two ileum contractions. The conclusion is that the Mangosteen Skin Ethanol Extract works similarly to Papaverine Hydrochloride which is an antidiarrheal drug used to relax smooth muscles so that it can also make blood vessels dilate by relaxing smooth muscles in the walls of blood vessels.

Bioengineered in vitro Vascular Models for Applications in Interventional Radiology

2019 ◽  
Vol 24 (45) ◽  
pp. 5367-5374 ◽  
Author(s):  
Xiaoyun Li ◽  
Seyed M. Moosavi-Basri ◽  
Rahul Sheth ◽  
Xiaoying Wang ◽  
Yu S. Zhang
Keyword(s):  
Interventional Radiology ◽  
Animal Models ◽  
Blood Vessels ◽  
In Vitro Models ◽  
The Past ◽  
Endovascular Interventions ◽  
Conventional Animal ◽  
Vascular Structures

The role of endovascular interventions has progressed rapidly over the past several decades. While animal models have long-served as the mainstay for the advancement of this field, the use of in vitro models has become increasingly widely adopted with recent advances in engineering technologies. Here, we review the strategies, mainly including bioprinting and microfabrication, which allow for fabrication of biomimetic vascular models that will potentially serve to supplement the conventional animal models for convenient investigations of endovascular interventions. Besides normal blood vessels, those in diseased states, such as thrombosis, may also be modeled by integrating cues that simulate the microenvironment of vascular disorders. These novel engineering strategies for the development of biomimetic in vitro vascular structures will possibly enable unconventional means of studying complex endovascular intervention problems that are otherwise hard to address using existing models.

Activation of bovine oocytes by protein synthesis inhibitors: new findings on the role of MPF/MAPKs†

2021 ◽  
Author(s):  
Cecilia Valencia ◽  
Felipe Alonso Pérez ◽  
Carola Matus ◽  
Ricardo Felmer ◽  
María Elena Arias
Keyword(s):  
Protein Synthesis ◽  
Kinase Activity ◽  
Cyclin B1 ◽  
Protein Synthesis Inhibitors ◽  
Vitro Fertilization ◽  
New Findings ◽  
Bovine Oocytes ◽  
Dependent Pathway

Abstract The present study evaluated the mechanism by which protein synthesis inhibitors activate bovine oocytes. The aim was to analyze the dynamics of MPF and MAPKs. MII oocytes were activated with ionomycin (Io), ionomycin+anisomycin (ANY) and ionomycin+cycloheximide (CHX) and by in vitro fertilization (IVF). The expression of cyclin B1, p-CDK1, p-ERK1/2, p-JNK, and p-P38 were evaluated by immunodetection and the kinase activity of ERK1/2 was measured by enzyme assay. Evaluations at 1, 4, and 15 hours postactivation (hpa) showed that the expression of cyclin B1 was not modified by the treatments. ANY inactivated MPF by p-CDK1Thr14-Tyr15 at 4 hpa (P < 0.05), CHX increased pre-MPF (p-CDK1Thr161 and p-CDK1Thr14-Tyr15) at 1 hpa and IVF increased p-CDK1Thr14-Tyr15 at 17 hours postfertilization (hpf) (P < 0.05). ANY and CHX reduced the levels of p-ERK1/2 at 4 hpa (P < 0.05) and its activity at 4 and 1 hpa, respectively (P < 0.05). Meanwhile, IVF increased p-ERK1/2 at 6 hpf (P < 0.05); however, its kinase activity decreased at 6 hpf (P < 0.05). p-JNK in ANY, CHX, and IVF oocytes decreased at 4 hpa (P < 0.05). p-P38 was only observed at 1 hpa, with no differences between treatments. In conclusion, activation of bovine oocytes by ANY, CHX, and IVF inactivates MPF by CDK1-dependent specific phosphorylation without cyclin B1 degradation. ANY or CHX promoted this inactivation, which seemed to be more delayed in the physiological activation (IVF). Both inhibitors modulated MPF activity via an ERK1/2-independent pathway, whereas IVF activated the bovine oocytes via an ERK1/2-dependent pathway. Finally, ANY does not activate the JNK and P38 kinase pathways.

scholarly journals The Current Challenges for Drug Discovery in CNS Remyelination

2021 ◽  
Vol 22 (6) ◽  
pp. 2891
Author(s):  
Sonia Balestri ◽  
Alice Del Giovane ◽  
Carola Sposato ◽  
Marta Ferrarelli ◽  
Antonella Ragnini-Wilson
Keyword(s):  
Drug Screening ◽  
Myelin Sheath ◽  
Time Window ◽  
In Vitro Models ◽  
Adult Brain ◽  
Pharmacological Intervention ◽  
Cellular Models ◽  
New Findings ◽  
Myelin Injury

The myelin sheath wraps around axons, allowing saltatory currents to be transmitted along neurons. Several genetic, viral, or environmental factors can damage the central nervous system (CNS) myelin sheath during life. Unless the myelin sheath is repaired, these insults will lead to neurodegeneration. Remyelination occurs spontaneously upon myelin injury in healthy individuals but can fail in several demyelination pathologies or as a consequence of aging. Thus, pharmacological intervention that promotes CNS remyelination could have a major impact on patient’s lives by delaying or even preventing neurodegeneration. Drugs promoting CNS remyelination in animal models have been identified recently, mostly as a result of repurposing phenotypical screening campaigns that used novel oligodendrocyte cellular models. Although none of these have as yet arrived in the clinic, promising candidates are on the way. Many questions remain. Among the most relevant is the question if there is a time window when remyelination drugs should be administrated and why adult remyelination fails in many neurodegenerative pathologies. Moreover, a significant challenge in the field is how to reconstitute the oligodendrocyte/axon interaction environment representative of healthy as well as disease microenvironments in drug screening campaigns, so that drugs can be screened in the most appropriate disease-relevant conditions. Here we will provide an overview of how the field of in vitro models developed over recent years and recent biological findings about how oligodendrocytes mature after reactivation of their staminal niche. These data have posed novel questions and opened new views about how the adult brain is repaired after myelin injury and we will discuss how these new findings might change future drug screening campaigns for CNS regenerative drugs.

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