AUCTORES
Globalize your Research
Review | DOI: https://doi.org/10.31579/2578-8949/082
Consultant Dermatologist, Royal Wolverhampton NHS Hospitals. United Kingdom
*Corresponding Author: Mohammed S Al Abadie PhD FRCP, Consultant Dermatologist, Royal Wolverhampton NHS Hospitals. United Kingdom.
Citation: Mohammed S Al Abadie. (2021) The Neuronal Theory in the Pathogenesis of Vitiligo: Past and Present. J. Dermatology and Dermatitis. 6(3); Doi:10.31579/2578-8949/082
Copyright: © 2021 Mohammed S Al Abadie, 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: 16 August 2021 | Accepted: 28 August 2021 | Published: 10 September 2021
Keywords: Vitiligo; Neuronal Theory; Neuropeptide Y (NPY); Neuropeptides
Vitiligo is a common skin disorder with an estimated prevalence of 1-2% of the world population. It is characterised by well demarcated milky white patches of depigmentation which have the tendency to enlarge and spread peripherally. The pathogenesis is not fully understood, a process leads and end in the loss of functional melanocytes from the epidermis. There are many proposed theories and hypotheses, none of which can fully explain its pathogenesis. However, lately it is believed that an overlap between some of these theories can present better understanding. This is to include the two long standing theories i.e., the autoimmune and the neuronal. The latter been proposed in 1959, initially based on clinical observations and studies, including animal, physiological, biochemical, embryonic, structural and electron microscopy. In 1994 new evidence emerged linking the neuronal theory to autoimmune mechanisms by demonstration of changes in Neuropeptides in particular Neuropeptide Y (NPY), in the skin at the active edge of vitiligo skin. This review paper highlights all evidence supportive of the neuronal theory in the pathogenesis of vitiligo past and present.
Vitiligo is a common idiopathic skin disorder w hich can affect 1-2% from any population, although it is reported to be significantly higher in certain populations. Vitiligo is characterized by progressive circumscribed patches of depigmentation which have the tendency to enlarge and spread peripherally. Basically, this is due to the loss of functional melanocytes from the epidermis. The exact pathogenesis of vitiligo is still not fully understood, hence there are many theories and hypothesis been proposed including the autoimmune, Neuronal, melanocyte self-destruction, or defective adhesion, degenerative, composite and convergence. Non can explain all pathophysiology, however, lately it is believed that there is an overlap or link between some of these theories to fully understand the complete picture of vitiligo pathogenesis.
The Neuronal theory was first introduced by Lerner in 1959. He postulated the neuronal theory in the pathogenesis of vitiligo. He proposed that the nerve ending in the skin release substance which can be cytotoxic leading to the destruction of the Melanocytes. Initially it was thought this Catecholamines possibly others. The hypothesis was mainly based on theoretical proposition and many clinical observations (presented and discussed in this research).
The study presents for the first time the whole evidence supporting the neuronal theory from when it was first proposed into the most recent supporting evidence including the role of neuropeptides in the process of autoimmune events leading to the destruction of the melanocytes.
Prior the mid-nineties the neuronal theory proposed by Lerner in 1959 [1], was mainly supported by several clinical observations and backed up by a number of embryonic, structural, biochemical, physiological and animal studies. In 1994 [2] the Neuronal theory been boosted with the discovery of the link of Neuropeptides and in particular Neuropeptide Y (NPY) in the pathogenesis of vitiligo. It was postulated that upon specific factors the release of such peptides can initiate a cascade of events where it can trigger the immune system in a process leading to the destruction of the melanocytes in a genetically predisposed individuals. Hence this has linked the neuronal and the autoimmune theories in the pathogenesis of vitiligo [2].
Clinical Observations and Studies
The concept of neuronal involvement in vitiligo is largely based on clinical observations. The most important of these is the finding of segmental distribution of depigmentation in some patients. Segmental does not mean dermatomal and usually several different dermatomes or a portion of one is involved. The depigmented segment has a nevoid appearance and usually, though not invariably, unilateral [3]. Each depigmented lesion stops abruptly at the midline [3].
However, vitiligo has on occasion been reported in a definite dermatomal location, eg confined to the distribution to the trigeminal nerve [1]. The symmetrical distribution of the lesions also gives important evidence for neuronal involvement. In a patient with transvers myelitis paralyzed from the waist down, hypopigmentation was not spared in the areas below the level of cord damage, and vitiligo lesions only developed on the face [4] and upper portion of the body, ie the neck, axillae, arms and hands [1]. This distribution would be unusual for a patient with generalized vitiligo. Furthermore, it was unusual that the koebner reaction did not result in the surgical scar when hysterectomy was carried out on this patient. Vitiligo has also been reported following peripheral nerve injury [5], in a child with viral encephalitis [6], and in patients with multiple sclerosis who had Horner’s syndrome [7]. Spontaneous re-pigmentation of extensive vitiligo has been observed in a diabetic patient who developed sever diabetic neuropathy [8]. A further supportive case is that of a patient who developed a traumatic injury to the right brachial plexus, who exhibited ipsilateral macules of vitiligo at the level of the upper arm, chest, buttock, sacrum and scrotum [9]. The author suggested the phenomenon of sympathetic repercussion has resulted in the widespread leukoderma and that irritation of the sympathetic nerve endings of the C8 and D1 roots has induced a series of reflexes which resulted in depigmentation exceeding the area innervated by the brachial plexus.
Surgical transplant studies have also given support to the neuronal concept of vitiligo. Haxthausen [10] transplanted skin from pigmented to non-pigmented area and vis versa. He showed that transplanted skin always taken the characteristics of the area into which the graft is placed but that this only happens after the local innervation has been re-established. Others have made similar findings [11].
Lerner (1) postulated that vitiligo probably resulted from increased output at the peripheral nerve endings of a substance that lightens melanocytes. This view is shared by Panja [12] who suggested that melanocytes become devoid of their function as a consequence of dysfunction or damage to autonomic nerve components. He regarded vitiligo as “trophoneurosis” affecting the adreno-autonomic system. The link of vitiligo to emotional trauma and stress has added an extra value and strength to the clinical observation in support of the neuronal theory.
Animal Studies
The neuronal influence on the skin color of certain animals is well known. In the lower animals there is direct adrenergic response and the melanophores were found to have direct innervations [13, 14]. In fish electrical stimulation of cutaneous nerves causes blanching, and sectioning the nerve cause darkening. Pigment cells of fish, amphibians and reptiles have alpha-and/or beta- adrenergic receptors. Alpha stimulation lightens the skin by the aggregation of melanosomes, and stimulation disperses granules to cause darkening [15]. In frogs, the pigment cells are not innervated directly, yet these cells, like those in lizards respond to pharmacologically active adrenergic and cholinergic chemicals as well as their blocking agents [16] Parker [17] examined the dark dorsal and pale ventral skin of the cat fish (Ameirus) and found a higher concentration of acetylcholine in the dark portions compared to the pale areas. Furthermore, Fabian [18] showed an alteration of cutaneous pigmentation when denervating the skin in guinea pigs. Acetylcholine, noradrenaline, adrenaline and melatonin were found to have a lightening effect on the dermal melanocytes in the frog and in other marine animals [1]. In a study on inbred black rats white hair after the injection of Adrenaline / Epinephrine [19].
Physiological and Biochemical studies
The clinical observation of a link between the nervous system and vitiligo initiated many physiological and biomedical studies. Chanco-Turner and Lerner [20, 21] measured the surface temperature, sweat production and bleeding time in vitiliginous skin and compared it to normal. Their study showed the temperature and sweat production vitiliginous skin and compared to normal. Their study showed that the temperature and sweat production in vitiliginous skin were increased, and the bleeding time was prolonged. However, injection of acetylcholine and adrenaline (at a concentration of 1;10,000), as well as of histamine (1:100,000) into the vitiliginous and normal skin did not reveal any difference in the wheal and flare reaction or, following injection of acetylcholine, in sweat production [20]. Likewise, sweat production after the injection of adrenaline and the triple response to histamine was the same in both vitiliginous areas exhibited either excessive cholinergic activity or relatively insufficient adrenergic tone [20]. Other studies have also shown abnormalities in such parameters as blister to the injection of adrenaline [22]. Dutta also concluded that vitiliginous skin had an impaired sympathetic adrenergic tone. Koga [23], studying patients with segmental or generalized vitiligo, found the reaction to injections of physostigmine, an inhibitor of cholinesterase, was far higher in segmental vitiligo patients compared to that in patients with generalized vitiligo. The treatment of segmental vitiligo with nialamide, a monoamine oxidase inhibitor, produced re pigmentation in 16 out of 28 patients (55%) [23]. The conclusion from this study was that the depigmented skin of patients with early stage segmental vitiligo exhibits adrenergic hypotonia; in a later stage, hyperactive adrenergic response is noted.
The axon reflex sweat secretion test with nicotinic tartrate (1:100,000 dilution) and the surface temperature were reported to be alerted in vitiliginous skin compared to normal [24]. Altered autonomic function in vitiliginous skin has also been found [1, 25, 26]. In Contrast, another study showed no difference in cutaneous sensation and perspiration between vitiliginous and normal skin: intradermal injection of acetylcholine (1:60,000) showed the same degree of sweating in both types of skin [27].
Biochemical studies have showed that pathways for the metabolism of the amino acid tyrosine and its oxidative derivative, dopa, are the substrates for both melanin and the neurotransmitters adrenaline and non-adrenaline [3].
Embryonic, Structural and Electron Microscopy Studies
Melanocytes and nerve cells are both derived from the neural crest and melanocytes are thought to migrate towards the epidermis at the third trimester [1, 28, 29]. Melanoblast migrates from the dorsal area of the neural tube to the basal layer of the epidermis, and hair bulb, inner ear, uvea and meninges [30]. This may also explain how the outer root sheath acting as a source of reservoir for repigmentation in Ultra Violet therapy in vitiligo. In segmental vitiligo a degree of sympathetic verve disfunction was found [31]. The production of pigment and melanocytic development are directly regulated by local sympathetic adrenergic innervation, an increased activity of which has been shown in vitiligo lesions [32]. In vitiligo, a direct anatomical contact between nerve fibers and melanocytes has been seen [33].
Shao Chan-Gen [34], using a silver impregnation technique, described dystrophic changes among the nerve trunks and terminals in vitiligo lesions. He reported a significant difference in intensity of staining of nerve fibers in lesions with a very long duration. Furthermore, an electron microscopic study by Breathnach [35] showed degenerative and regenerative changes in the terminal regions of the nerve supply, and in central and marginal areas of vitiliginous lesions. Other studies have also demonstrated degenerative changes in the nerves of vitiligo lesions [36, 37]. Further Electron Microscopy Studies on skin peripheral nerves in vitiligo show significant changes. An increase thickness of the basement membrane of Schwann cells in 75% of patients compared to normal skin control, 50% of the abnormal dermal nerves in vitiligo showed minor axonal damage [38].
Morphological and functional link was also found between the Melanocytes and nervous system [39]. In an acute active vitiligo skin, significant degeneration was found in dermal nerves. Complete degeneration of the nerves seen in 41% of patients, 38% showed partial degeneration. Nerve ending showed similar pattern [40].
Emotional Trauma and Stress
The onset of vitiligo sometimes is associated with severe emotional trauma such as the death of parent or spouse, the loss of a job, financial ruin, or a sever fright, and extension of the disease often occurs when the patient experiences great stress. Supportive case histories include that of a young girl, nearly struck by a gunfire in a war who became suddenly aware of having vitiligo [41]. Another is that of a hysterical woman who complained of pain in the back of right thigh and who developed urticaria and vitiligo after the insertion of electromyographic needles [42]. Clinical impression as well as patients’ views often relate the disease’s initial attack or subsequent flare-up to severe stressful event, usually emotional in character, such as marital quarrel, death of loved one, tension at work or a frightening accident [1, 43, 44]. In one study 69%of the patients either claimed an emotional upset preceded their vitiligo or attributed their disease to nervousness, an accident, illness, an operation or parturition [1]. Acute vitiligo has been reported after an emotionally traumatic event [29]. Furthermore, vitiligo is also associated with severe emotional trauma such as the death of a parent or spouse, the loss of a job, financial ruin, or a sever fright, and extension of the disease often occurs when the patient experiences great stress. Supportive case histories include that of a young girl, nearly struck by gunfire in a war, who became suddenly aware of having vitiligo [41]. 30% of patients reported significant emotional and stressful life events preceding the initial onset of the vitiligo with 39% report flare ups with stress [1]. Vitiligo patients mentioned personal problems in 47% of cases on third were related to exams, and 31% of cases were related to jobs or financial problems [45]. On the other hand, vitiligo can have psycho-social impact on sufferers [46, 47, 48]. The prevalence of vitiligo is reported to be higher in psychosis clinics rather that in dermatology clinics [49]. Vitiligo is said to typically occur in tense, emotionally liable people [1, 21].
Nerve Growth Factor (NGF)
Nerve Growth Factor (NGF) release by keratinocytes was found to have a significant effect on melanocytic migration [50]. In skin NGF has an important role in the maintenance of sympathetic nerve fibers [51]. The significant upregulation in expression of p75 NGFr in vitiligo skin and the increasing evidence that NGF plays an important role between the nervous and immune systems, suggesting a potential role in the destruction of melanocytes in vitiligo patients [52]. Liu [53] showed a tendency for a reduction in the number and intensity of low affinity (p75) nerve growth factor receptor immuno-reactive (NGFr-IR) basal keratinocytes in involved vitiliginous skin compared with controlled skin, while the number of NGFr-IR nerve fibers was significantly increased [53].
Neuropeptides
In 1994 breakthrough research in Sheffield, using semi-quantitative immuno-histochemical methods, linked the neuronal theory to autoimmune mechanisms by the demonstration of changes in neuropeptides, especially neuropeptide Y, in the skin at the active edge of vitiligo macules [2]. The authors proposed that neuropeptides, notably neuropeptide Y, release at the epidermal nerve ending release adjacent to melanocytes, provoke a local immune reaction leading to melanocyte destruction in predisposed individuals. Subsequent research has bolstered a role for neuropeptides and the neuro-immunological process in the causation of vitiligo in particular Neuropeptide Y (NPY) and possible role for others [51, 54, 55, 56]. The link of neuropeptides with catecholamines is well established [4]. The increase of catecholamines in vitiligo can contribute to the destruction of melanocytes by direct cytotoxicity or indirectly by causing severe vasoconstriction as a result of the activation of alpha receptors of the skin arterioles. This can lead to sever hypoxia leading to the production of toxic oxygen radicals and that can lead to the destruction of the melanocytes [57]. In vitiligo patient’s catecholamines neurotransmitters has an impaired metabolism. Plasma level of norepinephrine was significantly higher when compared to control [58]. Investigation of personality structures in patients with vitiligo and a possible association with impaired catecholamine. Norepinephrine and monoamine oxidase activities was also found to be increased in keratinocytes cultured from lesional and non lesional skin from vitiligo patients [59]. The level of Norepinephrine (NE), Normetanephrine (NMN), and their metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG), Homovanillic acid (HVA), were found to be significantly higher in Vitiligo patients at the active phase of the disease [60] Catecholamine was also found in elevated in serum and urine of vitiligo patients [61,62]. Neuropeptide Y (NPY), is found to be co-localized and released with direct link with norepinephrine from nerve fibers once stimulated. Furthermore, it can modulate the release and the effect of norepinephrine on the sympathetic nervous system [4)]. Dopamine is another precursor of catecholamines. Its plasma level was found to be significantly higher in vitiligo patients compared to control [63]. This can induce apoptosis of the melanocytes in vitiligo, possibly linked to stress [61], in association with the increase of sympathetic nerve stimulation triggered by NPY inducing vasoconstriction during stress [25], leading to the induction of a local immunological reaction [64], a process which can end up with the destruction of the melanocytes.
Significant elevation of plasma and tissue fluid level of NPY was found in vitiligo patients. The level of NPY in the patients with vitiligo of generalised-local and segmental vitiligo were found to be significantly higher than normal control. In both local and segmental type, the levels in progressive stage were significantly higher than those in stable stage [55].
More recently, it was concluded that Neuropeptides and nerve growth factors are critical regulators in of emotional responses participating in the onset and development of vitiligo in certain predisposed individuals. Direct cytotoxicity to melanocytes and the initiation and propagation of local and systemic immune or inflammatory reaction; include a specific adaptive immune response leading to the destruction of melanocytes which can be triggered by the following neurogenic factors i.e. NPY, CGRP, Catecholamines, NGFs and NGF receptors [51].
Centrally Neuropeptide Y (NPY), can act as a neuro-endocrine integrator where it links the central and peripheral nervous system by linking the hypothalamus, pituitary and gonadal axis [65]. The reduced level of NPY in brain central amygdale lead to anxiety [66], while on the other hand NPY is also involved in stress response and mood swings proved by the studies showing the increase of (NPY) expression and release in the brain, indicating this can be directly involved with the emotion and mental stress [67]. Subsequently, emotional and mental stress can play a significant role in the production of cytokines and reactive oxygen spices (ROS), by triggering an inflammatory response initiated by antigen-presenting cells (APC), and Polymorphonuclear leukocytes (PMN). The process may well lead to the destruction of the melanocytes [51].
It is thought that Neuropeptides eg (NPY) has a direct interaction with the T cells, triggering events lead to the induction of Cytokines secretion phenotype [68, 69]. NPY, can affect the functions of the cells of the adaptive and innate immunity. In this respect, NPY is known to modulate immune cell trafficking, T helper cell differentiation, cytokine secretion, natural killer cell activity, phagocytosis, and the production of oxygen species. The specific Y receptors have been found in immune cells, and their expression is amplified upon immune stimulation [64].
Another Neuropeptide ie Calcitonin Gene Related Peptide (CGRP) which was also found to have a link between the nervous and immune system. It can be involved in chronic inflammatory responses which can trigger specific adaptive immune responses leading to the destruction of the melanocytes in general [51]. A role for CGRP release from the sympathetic nerve endings in the skin triggered by emotional stress and anxiety is also proposed in the distraction of the melanocytes by triggering a local and systemic inflammation by direct activation of keratinocytes, Langerhans cells, and glial cells in the skin. CGRP can also trigger the production of Catecholamines by stimulating hypothalamus-pituitary-adrenal axis [51, 70, 71]. CGRP nerve fibers were found to be significantly increased in the epidermis and papillary dermis involved vitiligo skin compared with controlled skin [54, 53]. Other neuropeptides role in the pathogenesis of vitiligo is not clear and that include, Vasointestinal Peptide (VIP) questioning its presence at vitiligo skin [2], or the effects on the immune cells [72, 73].
It is proposed that Neuropeptides release provoking local immune reaction leading to the destruction of Melanocytes, in a genetically predisposed individual. Such link was confirmed where an increase level of Neuropeptide Y (NPY) in a specific population with vitiligo was found to be associated with genetic variant of interleukin 1B (IL1B). Further work is needed to explore the relationship of neuropeptides and the process of keratinocyte stimulation by interferone- γ producing CXCL9/10 leading to the recruitment of the melanocytotoxic T cells. Blocking such process by Janus kinase (JAK)-1 inhibitors might be the key to stop the cascade of events leading to the destruction of the melanocytes.
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.
