AUCTORES
Globalize your Research
Review Article
*Corresponding Author: Vinod Kumar Gupta, Physician-Medical Director, Migraine-Headache Institute, Gupta Medical Centre INDIA.
Citation: Vinod Kumar Gupta. (2023). Eclampsia in the 21st Century: Paradigm Shift from Empirical Therapy with Magnesium Sulfate. Basic Science Synthesis vs. Current Who-Recommended Pharmacotherapeutic Practice. J. Brain and Neurological Disorders. 6(2): DOI:10.31579/2642-973X/045
Copyright: © 2023 Vinod Kumar Gupta, This is an open-access article distributed under the terms of The Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 07 November 2022 | Accepted: 02 December 2022 | Published: 30 January 2023
Keywords: preeclampsia; eclampsia; magnesium sulphate; who; blood-brain barrier; hypertension; cerebrospinal fluid; cytokines; tumor necrosis factor-α; albumin-cytological dissociation
Pathophysiology of preeclampsia / eclampsia is not clearly understood and its management with WHO recommended mega-doses of intravenous magnesium sulfate appears empirical or experiential. A characteristic albumin-cytological dissociation prevails in the cerebrospinal fluid (CSF), indicating a pressure-related hyperpermeability rather than disruption of blood-brain barrier (BBB). Hypomagnesemia, absolute or relative, is not specific or unique to seizures of preeclampsia / eclampsia. Magnesium is regarded as ideal drug for managing eclampsia but does not guarantee control of convulsions in a significant fraction. The pharmacokinetics and pharmacodynamics of magnesium are only partially understood. Magnesium does not freely cross the intact BBB, reduces permeability of BBB following large exogenous doses given intravenously in diverse experimental circumstances, and has no ‘central’ anticonvulsant action. Magnesium in large doses depresses the skeletal neuromuscular junction while sparing autonomic innervation and all brain functions, occasionally inducing a pseudo-coma like condition with flaccid quadriparesis but without impairment of cognition or consciousness. Cerebral arteries and CSF maintain a much higher level of ionic magnesium than systemic arteries, indicating the operation of distinct systemic and CNS compartments of magnesium controlled meticulously for brain homeostasis. Failure of CSF magnesium levels to rise in correspondence with mega-doses given intravenously is the clearest evidence against a clinically significant functional disruption of the BBB. Higher levels of low molecular albumin and dextran in CSF indicate a hypertension-related hydrostatic pressure mediated hyperpermeability. Cytokines and TNF-α70 are generated by the brain immune system, govern neuronal plasticity, and their elevated levels in the CSF do not indicate physical BBB disruption. A magnesium-related cause-effect-adaptive pathophysiologic continuum prevails in preeclampsia and eclampsia. Relative decrease of magnesium in plasma or CSF is not specific to preeclampsia or eclampsia and forms the adaptive limb of this continuum. Hospitalization itself is the commonest cause of hypomagnesemia. Seizure or convulsion is a life-threatening disorder with possibility of sudden death. Hypomagnesemia allows supraoptimal function of all body function linked to calcium ions in all circumstances, including eclamptic convulsions. Administration of magnesium in ICU in the face of myocardial infarction, pulmonary edema, or pump failure is clearly hazardous. Eclampsia is a self-limited disorder that can resolve spontaneously with delivery and complicates decisive evaluation of potential anti-seizure agents, including magnesium. Magnesium has saved lives and reduced morbidity in preeclampsia / eclampsia as a ‘peripheral’ anticonvulsant, a unique clinico-pharmacologic situation.
CA++ -- calcium ions
CNS – central nervous system
BBB -- blood-brain barrier
CSF – cerebrospinal fluid
i.v. – intravenous
LMWS – low molecular weight substances
Mg++ -- magnesium ions
MRI -- magnetic resonance imaging
s-NMJ –skeletal neuromuscular junction
TNF-α – tumor necrosis factor-alpha
WHO – World Health Organization
Box 1. 10 key learning points:
Eclampsia remains the major cause of morbidity and mortality (death or near miss) for both the mother and the baby representing one of the principal reasons for admission to intensive care unit (ICU), with a lesser incidence in developed countries that, paradoxically, limits clinical experience with the disease and its complications. [1-5] Eclampsia is characterized by self-limited and unpredictable generalized tonic-clonic seizures not attributable to any other cause. Eclamptic seizure occurs in 2% of women with severe preeclampsia not receiving magnesium sulfate and in <0>
The biology of an illness “...is indivisible, has always been holistic in the sense that it considers the whole patient, has always seen the patient balanced between opposing forces pushing her/him towards health or disease as well as considered the ability to continue to function in the face of acute injury or disease process(es) (e.g. preeclampsia / eclampsia), and generates variations in the effects of the same injury/disease in the same individual from time to time just as between individuals”. [6,7] “Such a clinical continuum is unlikely to be unifactorial or a ‘hopelessly complex’ obfuscation, but is probably the result of a meticulously parallel activation of multiple physiologic processes (secondary or adaptive) processes...is not synonymous with ‘physiological’ ‘organic’, ‘laboratory measurements’ or ‘nonenvironmental’ as has often seemed the case in the medical literature”. [6,7] To make meaningful progress in understanding biological nature or pathophysiologic basis of preeclampsia / eclampsia, an overarching, robust, generalizable, and biologically-plausible clinically-valid cause-effect-adaptive continuum needs to be evolved. Besides supportive care and promoting delivery, magnesium sulfate is regarded as an ideal drug for the prevention and treatment of eclampsia, as recommended by the World Health Organization towards achieving the Millennium Development Goals [8].
While the best intravenous (i.v.) therapeutic regimen and the ideal duration of maintenance therapy of Mg are not yet clarified, supraphysiological serum levels between 4 and 7mEq/L do not guarantee that pregnant women with hypertensive disorders are protected against eclampsia. [1-5] In one study, oliguria was the commonest maternal complication recorded with i.v. infusion of magnesium sulfate at 1 gram/hour or 2 grams/hour as a maintenance dose for the prevention of eclampsia. [2] (Discussed below) The basis of adverse neonatal effects seen in women exposed to magnesium sulfate is speculative, and, intriguingly, outcome does not differ in newborn infants at either 1 gram/hour or 2 grams/hour maintenance doses, except for admission to neonatal intensive care, which was more frequent in the 1-gram/hour group (25% vs 6.3%; P=.04). [2] In-depth knowledge of the pharmacokinetics and pharmacodynamics of magnesium sulphate infused i.v. is required for a definitive understanding of the state of dynamic equilibrium between dose administered, its distribution and elimination rate, its efficacy in eclampsia, its side effects in both the mother and the neonate, and to move beyond presumed therapeutic algorithms or clinical suppositions. Such knowledge is missing. [1-5] Only 1% of the total body Mg pool is extracellular, as reviewed. [6,7] Hypomagnesemia in plasma or CSF does not predict eclampsia. To date, there is dearth of data and comprehension regarding Mg transport across BBB, an important caveat for elucidation of pathophysiology of preeclampsia / eclampsia.
Does exogenously administered magnesium in large intravenous doses freely cross the intact or hyperpermeable blood-brain barrier?
The BBB tightly regulates homeostasis of the central nervous system (CNS). Elevated levels of Mg do not freely cross the intact BBB and, conversely, reduce BBB permeability to maintain brain homeostasis in a variety of clinical and experimental circumstances, including acute hypertension and idiopathic epilepsy. [6,7,9-11] Low levels of serum Mg prevail in acute and chronic neuronal (ischemic stroke, inherited, and neurodegenerative diseases) and extra-neuronal diseases in hospitalized patients as well as in stress and anxiety, as reviewed elsewhere. [6,7,9-11] A protective role of Mg on the BBB itself to reduce its permeability has been presented in vivo and in vitro model of human BBB possibly related to remodelling of intercellular gap formation, as reviewed recently. [2,6,7] Exogenous i.v. administration of magnesium sulphate in 10 preeclamptic patients maintained mean CSF Mg level in the normal range (3.04 +/- 0.12 mg/dl, range 2.9 to 3.2 mg/dl). [11] In another study of preeclamptic women, CSF ionized, total Mg, and Ca++: Mg++
ratios did not change following magnesium sulphate therapy. [12] Basal levels of free Mg++ in CSF are three times that in plasma while the walls of the cerebral arteries have almost double the content of free Mg++ seen in systemic arteries. [13] Such an ‘adaptive’ or ‘protective’ distribution of Mg++ is designed to tightly restrict access of exogenously administered Mg into CSF / CNS in order to maintain a critical functional balance between systemic and brain compartments. [6,7] These data indicate that following administration of large pharmacologic doses of Mg in preeclampsia / eclampsia, access of Mg to CSF/CNS is dampened, and that there cannot be any direct relationship between serum and CSF magnesium values. [6,7]
The postulate that exogenously administered Mg does not critically affect brain neuronal function in preeclampsia / eclampsia or in any other brain neuronal disorder cannot be overemphasized and is sustainable both pharmacologically and biologically.
Is blood-brain barrier disruption / hyperpermeability established in eclampsia?
BBB disruption and/or a generalized hyperpermeability has been suggested to prevail in eclampsia by increased CSF concentrations of pro-inflammatory cytokines (IL-6 and IL-8) and TNF-alpha compared to women with normotensive pregnancies (n = 7) and also by elevation of CSF levels of interleukin-6 and TNF-alpha compared to women with preeclampsia (n = 4). [1] Women with preeclampsia also showed increases in pro-inflammatory cytokines but not TNF-alpha in the CSF compared to women with normotensive pregnancies. [1] In particular, women with eclampsia but also women with preeclampsia showed an increase in the CSF to plasma albumin ratio compared to normotensive women. [1] The conclusion that women with preeclampsia and eclampsia show evidence of neuroinflammation and an injured BBB opens a crucial debate.
The human brain is not a passive receptacle to receive pro-inflammatory cytokines and TNF-alpha exclusively from the systemic circulation in diverse circumstances. The brain has its own well-defined auto-immune system independent of the systemic auto-immune or inflammatory or both influences that may have evolved to maximize an organism's ability, anticipatory or contingent, to respond to environmental threats in order to survive without critical disruption of the BBB. Pregnancy is perhaps the best defined teleologic and evolutionarily conserved physiologic organ system that anticipates needs of the mother as well as the neonate. Resident brain cells produce immune system neuromediators such as cytokines, and both systems (nervous and immune) exhibit similar mechanisms of physiologic intercellular communication. [13] Neurons, astrocytes, and microglia produce cytokines and their receptors able to modulate synaptic plasticity, as well as the processes of learning and memory under normal physiologic conditions. [14,15] TNF-α is a critical orchestrator in modulating sensory deprivation-induced homeostatic plasticity in human basal forebrain and mammalian (mouse) olfactory cortex. (16,17) Variable elevations of pro-inflammatory cytokines and TNF-alpha in the CSF can originate from the brain itself under physiologic and stimulated states. Elevation of CSF albumin in preeclampsia / eclampsia results from a non-specific pressure-related movement of a low molecular weight substances (albumin, dextran) following the inextricably linked significant pressure gradient of moderate-to-severe systemic hypertension transferred to small vessels, that, in turn, selectively increases BBB permeability without enhanced diapedesis and can lead to cerebral edema. Rather than a total disruption of BBB integrity, (1) elevation of CSF albumin indicates enhanced hydrostatic pressure driven enhanced permeability. Total disruption of BBB would not sustain the albumin-cytological dissociation typical of preeclampsia / eclampsia. In an unambiguous or total disruption of the BBB, elevation of albumin would be accompanied by presence of red and white blood cells, besides other higher molecular weight substances. The terms BBB injury / impairment [1] must be qualified either as a hyperpermeability or a total non-selective disruption of BBB to reflect truer pathophysiologic status of integrity of BBB. Importance of reversal of such CSF changes following magnesium sulfate therapy [2] will always be questionable since eclampsia is itself a self-limited disorder terminated by delivery, the time frame of which termination is uncertain and variable, i.e., protean. MRI characteristics of brain edema may predict eclamptic seizures in preeclampsia patients with posterior reversible encephalopathy syndrome. [18] Currently, however, cerebral edema does not predict eclamptic convulsion.
In studies of BBB characteristics of preeclampsia / eclampsia, enhanced but selective permeability to low-molecular weight substances and the characteristic albumin-cytological dissociation must be specified. No correlation was also found between plasma angiogenic biomarkers and BBB permeability in preeclampsia. [18] Finally, following mega-dose intravenous Mg supplementation in preeclampsia / eclampsia, CSF magnesium levels do not follow serum magnesium levels correspondingly or at par as might be expected after significant or major pathophysiologic and functional disruption of BBB – probably the most representative, valid, and practical limitation for such theories. There appears to be no major functional or structural injury / disruption of the BBB peculiar or specific to preeclampsia / eclampsia besides the link to rise of hydrostatic pressure due to moderate-to-severe hypertension.
Magnesium and the neuromuscular junction: skeletal and autonomic innervations
Friedman-Korn et al. report reversible postpartum coma-like state following Mg therapy. [20] Besides unimpaired pupillary reflexes in the face of areflexic flaccid quadriparesis and absence of respiratory effort, [20] absence of obtundation or impaired consciousness suggests an extra-CNS prominent skeletal muscle side-effect of Mg infusion. Friedman-Korn et al. also report decremental responses on repetitive nerve stimulation in both women. [20] Dysfunction at the skeletal muscle neuromuscular junction (sNMJ), however, is characterized by an initial low-amplitude muscle action potential with progressive decline at low rates of stimulation followed by a progressive increase in amplitudes of successive responses (facilitation) at higher rates of stimulation and after isometric exercise. [21] Concomitant decrease in serum calcium level is important. [21] The variable intensity of sNMJ transmission defect in preeclamptic women receiving standard doses of Mg correlates significantly with increased serum Mg levels, decreased serum Ca levels, and is best correlated with the Mg/Ca ratio. [12,21] The particular predilection for pronounced NMJ dysfunction in some cases with pre-eclampsia admitted to ICU may involve markedly lowered plasma cholinesterase levels, subclinical thyroid dysfunction, and clinically-covert auto-immune disease. [21-23] Autonomic neuromuscular transmission, involving ATP, noradrenaline, or acetylcholine, is not involved by Mg. [24,25]. Besides pupillary reflexes, all ANS functions, including bowel and urinary bladder functions, remain unaffected by large doses of Mg. Magnesium oxide is an established laxative. [26] Magnesium decreases post-operative urinary retention. [27]. Anti-epileptic effect of large i.v. doses of Mg in preeclamsia / eclampsia probably involves a major generalized dampening effect on the sNMJ rather than a primary brain neuronal stabilizing influence.
Generalized vasodilator effect of magnesium in ICU
The primary Ca++ antagonist vasodilator function of Mg is not generally appreciated. [6,7,10,27,28] Magnesium administration increases cardiac output and minimises hypotension in patients without cardiovascular complications. The chronotropic and inotropic jeopardy of Mg supplementation manifests only in severe myocardial infarction with pump failure (left heart failure or cardiogenic shock or both) and deaths in ICU. [10,28,29] Oliguria following i.v. Mg supplementation for eclampsia [2] is another warning parameter in ICU indicative of diminished renal perfusion. Vasodilators, in general, do not decrease urine output. Oliguria is an established feature of severe preeclampsia. [1-5] Administration of 1-3g i.v. Mg before cisplatin is suggested as the best practice regardless of baseline serum Mg level to immediately increase urine output and to prevent cisplatin-induced acute kidney injury without reducing its chemotherapeutic efficacy. [30] Use of Mg in the ICU in general, and in eclampsia, therefore, must be guarded.
Currently, magnesium sulfate is the anticonvulsant of choice to treat or prevent eclampsia when indicated. WHO-recommended role of magnesium therapy in management of eclampsia, however, needs reconsideration. Exogenously administered magnesium does not freely cross the intact blood-brain barrier. A characteristic albumin-cytological dissociation is maintained in CSF in preeclampsia / eclampsia. Blood-brain barrier remains largely intact in preeclampsia / eclampsia with hydrostatic hyperpermeability to low molecular weight substances, including albumin and dextran. Failure of CSF magnesium levels to correspondingly rise following massive i.v. doses of magnesium are the clearest indication of maintenance of two homeostatic compartments of magnesium by the human body as well as of the functional integrity of the blood-brain barrier. Cytokines and tumor necrosis factor-α form part of the natural repertoire of the human / mammalian brain to develop and maintain plasticity. Anticipatory and contingent adaptation of the human brain to stress of moderate-to-severe hypertension of preeclampsia / eclampsia is crucial to evolutionary survival. Low / relatively low magnesium levels in serum and CSF despite large dose presumedly therapeutic infusion of magnesium sulfate form part of the cause-effective-adaptive continuum that maintains integrity of the organism in the face of life-threatening convulsions of eclampsia.
Expert Opinion
The BBB is the key structure that maintains a distinct compartment for magnesium at the level of the brain, to allow for a guarded milieu interior enabling optimal function of CNS neurons. The role of magnesium itself is critical in maintaining homeostasis at the level of the CNS. The development of systemic hypomagnesemia has to be viewed critically in clinical medicine, particularly in moderate-to-severe hypertension and with cardiac compromise. Act of hospitalization is the commonest etiology of hypomagnesemia in the systemic circulation. Magnesium content of cerebral arterial wall and CSF and is 200% to 300% that of systemic arterial wall, respectively. Transfer of magnesium across the BBB is carefully regulated to allow for adaptive CNS neuronal function under a wide spectrum of clinical circumstances. As the physiological antagonist of calcium ions (Ca++), magnesium ions (Mg++) importantly regulate BBB permeability and dampen transfer of Mg++ across the BBB. Following WHO-recommended regimen of massive infusion of magnesium sulfate for managing preeclampsia / eclampsia, CSF magnesium levels do not rise in parallel but remain within the normal range, a characteristic-to-pathognomonic neurotherapeutic laboratory feature. Hyperpermeability of BBB in preeclampsia with selective passage of low-molecular weight substances (LMWS) such as interleukins, tumor necrosis factor-α, albumin, and dextran is not tantamount to a total physico-chemical disruption of the BBB. Passage of LMWS into the CNS in preeclampsia / eclampsia possible involves a hydrostatic-pressure related transfer across the BBB. In addition, the brain has its own auto-immune system to manage synaptic plasticity, learning, and memory under normal physiologic conditions. A characteristic albumin-cytological dissociation prevails in preeclampsia / eclampsia. The WHO-guideline for role of magnesium therapy in management of self-limited convulsions of eclampsia is arbitrary and debatable. Magnesium does not have any intrinsic or generalized anti-convulsant activity. In supraphysiologic doses, magnesium depresses sNMJ function while sparing autonomic functions and brain functions, including cranial nerves, cognition, and consciousness, a unique and pathognomonic ‘pseudo-anticonvulsant’ action. Large pharmacologic doses of magnesium do not guarantee management of convulsions of eclampsia. As the distinction between ‘hyperpermeability’ versus ‘disruption’ of BBB in preeclampsia / eclampsia evolves, along with the concept of distinct ‘systemic or extra-CNS’ and ‘CNS’ compartments for magnesium in human neurophysiology, use of magnesium as an anticonvulsant in preeclampsia / eclampsia will be further rationalized. In the next five-years, I envisage that the physiology of magnesium at the level of CNS / CSF and / or the skeletal NMJ will be better understood
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
