Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

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On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



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Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
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Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




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Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




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Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Reviews
Year : 2007 | Month : August | Volume : 1 | Issue : 4 | Page : 312 - 324 Full Version

Gene Therapy: A Double-Edged Modality with Few Propitious Targets against Cardiovascular Disorders like Heart Failure, Hypertension and Infarction


Published: August 1, 2007 | DOI: https://doi.org/10.7860/JCDR/2007/.104
KHANNA A*, KHANNA R**

*Institute of Medical Technology, University of Tampere, Finland, E.U. **Regea Institute, University of Tampere, Finland.

Correspondence Address :
Dr. Anchit Khanna, M.B.B.S. M.S. (MEDICAL GENETICS). PhD Research Fellow, Institute Of Medical Technology, University of Tampere, Finland, E.U. Mob: +358-509342656; e-mail: Anchit.Khanna@uta.fi

Abstract

Cardiovascular diseases like that of congestive heart failure, hypertension and infarction have reached epidemic proportions, and even though many novel pharmacological formulations and devices have improved survival, a real cure is yet to be found. After extensive research and trials (both preclinical and clinical), gene therapy is seen as an important upcoming tool against cardiovascular disorders. Advancements in the vector technology and in the molecular understanding of various diseases like that of heart failure, ischaemic heart diseases and even polygenic diseases like hypertension have opened doors to a new era of cure. With the improved understanding of the pharmacodynamics and the pharmacokinetics of gene transfer, there is a substantial growth being seen in the treatment of cardiovascular disorders using gene therapy with an increasing number of potential targets (genes), especially in the post-human genome era. Few potential targets have been identified for gene therapy from various molecular pathways, which along with the newly developing delivery systems will accelerate and strengthen the fight against heart failure and ischaemia (therapeutic angiogenesis), in which at present most of the clinical trials are going on. But at the same time, all the potential adverse effects and safety concerns arising with these new modalities should also be assessed before enforcement

Keywords

Gene therapy/transfer,genetic targets, delivery systems

Introduction
Gene therapy is a therapeutic modality, which involves replacement of altered or non-functional gene with a healthy one. Indians have a genetic disadvantage when it comes to being affected by coronary disorders, because as an ethnic race, it tends to have a high lipoprotein(s) content compared to other races in the Asian region like that of Chinese(1). At present, the situation can be compared as a coronary epidemic, and the fact that in the past 30 years the average age of first heart attack in India decreased by 20 years (out of which men dominated the figures with over 50% of them being below 55 years and 25% being below 40 years) supports the statement (1). Heart being a localised organ makes it a potential target for surgical (or with the help of catheters) local in vivo gene delivery. The cardiomyocytes being post-mitotic cells require a prolonged and efficient gene expression, which is mainly met by vectors like adenoviruses, adeno-associated viruses and lentiviruses. The molecular pathways are again essential to identify the targets for the gene therapy for heart failure and also form the backbone for planning or bringing gene therapy into clinical practice.

Targets for Gene Therapy for Heart Failure
Target 1 – calcium channels (levels of calcium in the body)
Normally when an excitation impulse reaches the sarcoplasmic reticulum (SR) through the transverse (T) tubule, the voltage-gated calcium channels, longitudinal (L) type, open and allow small amount of calcium influx, which contributes to the calcium released by the SR through the Ryanodine receptors, which activates the myofilaments causing contraction of the myocardial muscle (Sliding Filament theory) (2). During relaxation, the SR re-accumulates the calcium back through the sarco-endoplasmic reticulum calcium ATPase pump
(SERCA2a), and then this calcium is pumped out extracellularly by the sarcolemmal Na/Ca exchanger(Table/Fig 1). In humans ≈75% of the Calcium is removed by the SERCA2a, while the remaining removed by the Na/Ca exchanger (3). This action of SERCA2a is inhibited by phospholamban protein (unphosphorylated state), while the phosphorylated state (cAMP and Ca-Calmodulin–dependent protein kinase) reverses this inhibition(4)(Table/Fig 2). The architecture of a functional sarco-endoplasmic reticulum with the location of the key players is shown in (Table/Fig 1).

Target 2 – apoptosis
In (Table/Fig 3), various signalling cascades are shown, which contribute to the mechanism of apoptosis (programmed cell death) of the cardiac myocytes, which in turn causes heart failure. These cascades include mitogen or stress-activated phospho kinases (SAPK) like p38, the p53 gene, and certain growth factors like insulin growth factor (IGF) 1, which inhibits other contributors like ischaemia and hypoxia.

Target 3 – β2 adrenergic receptors
There is quite a difference in the consequences of β2 adrenergic receptor (AR) stimulation and the β1AR formas, the basis of it being used as a target against failing heart (Table/Fig 4). Stimulation of the β1AR has an apoptotic arrythmogenic potential, whereas the β2AR signalling pathway is devoid of these negative effects (2). Therefore, using gene transfer for β2AR and βARK inhibitor will restore the cAMP levels, resulting in increased functionality of the cardiomyocytes.

Delivery<

Discussion

Experimental data and the information received from various ongoing clinical trials on gene therapy for cardiovascular disorders (many more in addition to the ones discussed in this dissertation) have been very encouraging, but again the searches for an ideal vector system, and even for the right gene, are still few of the major obstacles in our quest for a safe and efficient therapeutic modality against these disorders. For complex disorders like that of hypertension, more than one gene needs to be targeted and so what we can call a ‘therapeutic gene cocktail’ (20) should serve the purpose. The clinical trials for vascular gene transfer have not only shown it to be safe but also with lot of therapeutic potential when delivered intravascularly (20). But for future clinical trials, we must first test and find an efficient vector and study model (keeping in mind the good manufacturing practices). Then after the protocol approval and toxicological testing, we should bring it in for clinical trials and try in patients and human tissues. From 1989 (the first gene transfer) till present date, the technology has seen rapid progress in terms of yielding novel vectors and also the progress in clinical trials. Up to 2004, there have been 76 clinical trials for cardiovascular gene therapy, out of which 64 were for therapeutic angiogenesis (mainly involving FGF and VEGF genes) (21). At present, majority of the new trials in this field are in Phase I still, but with the development of specialised gene therapy units like that of University Of Pittsburgh (U.S.A.) and the A.I. Virtanen Institute for Molecular Sciences (Finland, Europe), to name a few, trials have entered phase II and some even phase III stages. The rationale at present against gene therapy as a therapeutic modality, especially after few setbacks like the famous Jesse Gelsinger death (which was attributed to the overdosage of drug), can be summarised by the joint statement issued by the American and European Gene Therapy Societies in response to an article in Nature, “The field of gene therapy is working to develop new and better methods to treat a variety of severe disorders, including genetic diseases such as hemophilia and SCID, and also cancer and AIDS. The clear-cut therapeutic benefits seen in recent clinical trials of gene therapy for XSCID and ADA-deficient SCID warrant judicious consideration of the benefits and risks of this approach compared to imperfect alternatives, such as haplo-identical hematopoietic stem cell transplantation.â€

GLOSSARY
Angiogenesis - Formation of a new blood vessel
AT1R/ATR - Angiotensin II type 1 receptor
ATP - Adenosine Tri-phosphate
Arrhythmia - Loss of normal rhythm
ANP - Atrial natriuretic peptide
Apoptosis - Programmed cell death
β1ARK - β1 adrenergic receptor kinase
Cardiomyocytes - Cells of the heart muscle
cAMP - cyclic adenosine mono-phosphate
Epicardium - Layer covering the heart
ECM - Extra-cellular matrix
FGF - Fibroblast growth factor
Glioma - Tumour of the glia (cells of the central nervous system)
Hyperplasia - Increase in number of cells
Hypernephroma - Tumour of the kidney
Ischaemia - Lack of blood supply
Intraluminal - Inside the lumen
LDL - Low-density lipids
Mitogen - Substance that stimulates mitosis
Myofilament - Muscle filament
Neoplasms - Cancers or tumours
ODN - Oligodeoxynucleotides
Sarcoplasmic reticulum - Cell organelle that controls the calcium levels
Transgene - The gene used in the gene transfer
TGF - Transforming growth factor
Therapeutic gene - Gene that is used for the purpose of treating the disorder
VCAM - Vascular cell adhesion molecule
VEGF - Vascular endothelial growth factor
Vector - Carrier of the protein/DNA (deoxyribonucleic acid)

Acknowledgement

A special thanks to Dr Douglas Wilcox, Honorary Consultant in Medical Genetics and Director of Education Yorkhill NHS Trust Glasgow, UK, for his guidance, and Dr. Andrew Baker , British Heart Foundation, Glasgow, UK. for his critical comments when the article was prepared as a part of my Masters thesis at University Of Glasgow, Scotland, UK. Also a special vote of thanks to my parents ( Anil Khanna and Usha Khanna) , Dr. Rishiv Jain, Brij Mohan Ajmani, and Aarohi Jain for inspiration and support.

References

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Iyer SN, Lu D, Katovich MJ, Raizada MK. Chronic control of blood pressure in the spontaneously hypertensive rat by the delivery of angiotensin type 1 receptor antisense. Proc Natl Acad Sci USA 1996;93:9960–5.
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