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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
Original article / research
Full Version
Correlation of Homocysteine, Paraoxonase 1 and Malondialdehyde in Healthy Elderly Population: A Cross-sectional Study
Correspondence Address :
Dr. Prachee Harishchandra Nirmale,
Plot 13A, Riddhi Siddhi Akashganga Co Op HSG SOC, Lavale, Pune, Maharashtra, India.
E-mail: phnirmale61@gmail.com
Introduction: There is rapid increase in the life expectancy worldwide. Altered metabolism and biochemical interactions between homocysteine, Paraoxonase 1 (PON1) and Malondialdehyde (MDA) result in development and worsening of various diseases of elderly population.
Aim: To correlate the levels of homocysteine, PON1 and MDA in healthy elderly population with respect to age, vitamin B12 and lipid profile.
Materials and Methods: The present cross-sectional study was conducted in Bharati Vidyapeeth (Deemed to be University) Medical College and Hospital, Pune, Maharashtra, India between July 2013 to July 2014. Study group consisted of 61 participants (30 elderly and 31 young healthy volunteers). Serum homocysteine and vitamin B12 were estimated by Chemiluminescence Microparticle Immunoassay (CMIA) while PON1 and MDA by spectrophotometry. Lipid profile was estimated by biochemistry autoanalyser. Statistical analysis was done by Pearson’s correlation coefficient.
Results: Homocysteine and PON1 levels were found to be lower in elderly participants than in young participants (p-value <0.05, <0.01). The levels of vitamin B12 and MDA were higher in elderly participants than in young participants (p-value <0.01, <0.01). The levels of Total Cholesterol (TC) (p-value <0.01), High Density Lipoprotein (HDL) (p-value <0.05) and Low Density Lipoprotein (LDL) (p-value <0.05) were statistically significantly high in elderly participants as compared to young participants. Statistically significant negative correlation of homocysteine with vitamin B12 levels in both elderly participants (p-value <0.01) as well as young participants (p-value <0.01) were observed. There was no statistically significant correlation between homocysteine and PON1 well as MDA in both the groups. There was statistically significant negative correlation between the levels of homocysteine and TC (p-value <0.05), HDL (p-value <0.05) and LDL (p-value <0.01) in elderly participants.
Conclusion: Elderly population is not at the risk of developing diseases whose risk factor is homocysteine. Males are at higher risk of development of diseases because of homocysteine than females of any age group. Homocysteine is not pathogenic in old age even in the presence of other risk factors such as lipid peroxidation, decreased defense mechanisms to lipid peroxidation, raised levels of atherogenic lipids and overweight. Improvement in the vitamin B12 status can decrease the homocysteine levels.
Atherogenic lipids, Chronic degenerative diseases, Vitamin B12
According to the Government of India; elderly or old age consists of ages 60 years or above. There is a shift in the pattern of leading causes of disease and death. This is characterised by the waning of infectious and acute diseases and the emergence of chronic and degenerative diseases. These diseases are Cardiovascular Diseases (CVD), cerebrovascular accidents, diabetic complications, ocular diseases, fractures and Alzheimer’s disease etc. Hyperhomocysteinemia is an independent risk factor and has causative role in CVDs like myocardial infarction (1), arterial and venous thrombosis (2), other coronary artery diseases (3),(4), arrhythmias (like atrial fibrillation and ventricular arrhythmia) and heart failure (5). Also, in diseases affecting central nervous system which are ischemic cerebral stroke (6), dementia and Alzheimer’s disease (7), other neurocognitive and psychological impairments (8) and psychiatric disorders like bipolar disorder (9). Homocysteine causes progression of diabetic retinopathy (10) and age related macular degeneration (11). Also, involved in osteoporotic fractures (12). Homocysteine is a sulphur containing amino acid formed from methionine. Hyperhomocysteinemia is involved in atherosclerosis, thromboembolism and vascular endothelial damage. It promotes formation of thrombin through activation of FactorV. Normally FactorV is associated with endothelial cells exclusively. But in atherosclerotic vessels it is associated with smooth muscle cells and macrophages (13). Homocysteine increases thrombomodulin synthesis at Ribonucleic Acid (mRNA) level and inhibits protein C activation. Thrombus formed from such homocysteinylated fibrinogen has a higher resistance for lysis. Hyperhomocysteinemia inhibits Deoxyribonucleic Acid (DNA) synthesis in vascular endothelial cells leading to neutrophil migration across the endothelial surface which adds to damage and detachment of endothelial cells. It also produces connective tissue changes in the arteriosclerotic plaques like fibrosis, calcification, proteoglycan deposition (14).
PON1 a calcium dependent multifunctional enzyme. It is a 355 amino acid glycoprotein synthesised in the liver and transported in plasma by binding to High-density Lipoprotein (HDL). PON1 was identified as an organophosphate-hydrolysing enzyme in mammalian tissue. PON1 has also been shown to metabolise a number of drugs and prodrugs via its lactonase activity. It destroys covalent linkages between lipid peroxidation products and Low-density Lipoprotein (LDL). PON1 also degrades hydrogen peroxide, a major Reactive Oxygen Species (ROS). Thus, PON1 has antioxidant and antiatherogenic activity. Hepatic expression of the PON1 gene is down regulated by hyperhomocysteinemia (15). MDA has been widely used for many years as a convenient biomarker for lipid peroxidation and oxidative stress. MDA is an end product of arachidonic acid and larger Poly-Unsaturated Fatty Acids (PUFAs). MDA is strongly reactive toward nucleophiles, such as basic amino acid residues (i.e., lysine, histidine and arginine) forming Advanced Lipid peroxidation End-Products (ALEs). ALEs promote intramolecular or intermolecular protein/DNA cross linking.
Under oxidative stress, MDA also undergoes oxidation by mitochondrial aldehyde dehydrogenase followed by decarboxylation to produce MDA Acetaldehyde (MAA) adducts. These MAA adducts are highly immunogenic (16).
It has been observed that biochemical interactions between homocysteine, PON1 and MDA result in development and acceleration of various diseases. Higher levels of homocysteine and MDA are correlated with lower levels of PON1. An increase in life expectancy should not only mean a decrease in mortality but it should also be in terms of maintaining a good ‘quality of life’. Mortality and disability of old age are mostly due to CVDs, cerebrovascular accidents, diabetic complications, ocular diseases, fractures and Alzheimer’s disease etc. Homocysteine is associated with these risk factors directly or indirectly (17),(18). So, reduction in homocysteine levels in middle aged and elderly adults will definitely help to increase life expectancy. So, this study was designed to understand the biochemical interactions between MDA, malodialdehyde and PON1 with respect to age, gender, vitamin status and Body Mass Index (BMI) etc.
This was a cross-sectional study, conducted at Bharati Vidyapeeth (Deemed to be University) Medical College and Hospital, Pune, Maharashtra, India, between July 2013 to July 2014. Institutional Ethical Committee (IEC) approval was obtained for the study. The study group was comprised of a total 61 participants. They were divided into two groups. Group I: The group comprised of 30 elderly healthy volunteers of age from 46 to 66 years of both genders. Group II: The group was comprised of 31 healthy young male and female volunteers of age from 15 to 45 years of both the genders.
The study was announced and willing individuals were asked for a specific history of any known condition as mentioned in exclusion criteria. Physical general and systemic examination was performed to measure the parameters required for the study and to confirm whether the history given was correct. Eligible individuals between the periods of two months were enrolled as a sample population and divided into two groups as stated.
Inclusion criteria for controls and cases: Healthy volunteers were included in the study
Exclusion criteria for controls and cases: Participants having conditions like women on hormone replacement therapy, pregnancy, history of CVDs, history of smoking and alcoholism, severe hepatic impairment, renal impairment, diabetes mellitus, hypothyroidism, malignancies. Participants on medications like vitamin B complex, Folate antagonists (Methotrexate, Phenytoin, Carbamazepine), vitamin B6 antagonists (Theophylline), Metformin, Diuretics, Nicotine were excluded from the study.
After obtaining written informed consent; participant’s detailed physical and clinical examination was carried out. BMI was calculated and interpreted by National Centre for Health Statistics age and gender specific percentile curves (19).
One mL of fasting blood sample (after 12 hours of overnight fast) was collected from antecubital fossa without venous occlusion in a plain vacutainer. Blood was allowed to clot for one hour. Serum was separated after centrifugation at 2000 rpm for 10 minutes at room temperature. Following parameters were estimated in the serum which were free from haemolysis and turbidity (Table/Fig 1) [20-23].
Statistical Analysis
Data obtained was statistically analysed by using Statistical Package for the Social Sciences (SPSS) software version 17.0. Statistical tests used are: Unpaired t-test for finding the difference in the mean value in the groups; Pearson’s correlation coefficient for finding correlation of homocysteine levels with PON1, MDA, vitamin B12 and lipid profile in both the groups. The p-value <0.01 and <0.05 was considered as significant.
There was statistically significant difference in the levels of homocysteine, vitamin B12, PON1 and MDA between two groups. Homocysteine and PON1 levels were found to be lower in elderly participants than in young participants (p-value <0.05, <0.01). The levels of vitamin B12 and MDA were higher in elderly participants than in young participants (p-value <0.01, <0.01) (Table/Fig 2).
There was statistically significant difference of weight and BMI between both the groups. The average weight was statistically significantly more in the elderly participants than young participants (p-value <0.01). According to BMI; elderly participants were overweight than young participants (p-value <0.01) (Table/Fig 2). The levels of TC (p-value <0.01), HDL (p-value <0.05) and LDL (p-value <0.05) were statistically significantly high in elderly participants as compared to young participants. There was no statistically significant difference in the levels of triglyceride (p-value 0.27) and VLDL (p-value 0.27) between the two groups (Table/Fig 2).
Statistically significant difference between the levels of homocysteine in male population of elderly participants (p-value <0.01) as well as young participants (p-value <0.05) as compared to female populations of both the groups was observed (Table/Fig 3).
Statistically significant negative correlation of homocysteine with vitamin B12 levels in both elderly participants (p-value <0.01) as well as young participants (p-value <0.01) was found. There was no statistically significant correlation between homocysteine and PON1 well as MDA in both the groups. There was statistically significant negative correlation between the levels of homocysteine and total cholesterol (p-value <0.05), HDL (p-value <0.05) and LDL (p-value <0.01) in elderly participants [Table/Fig-4,(Table/Fig 5),(Table/Fig 6)(a-c).
This study was designed to correlate the levels of homocysteine, PON1 and MDA in healthy elderly population as compared to healthy young population. Furthermore comparison of levels of lipid profile, weight and BMI between elderly and young participants was also done. In present study, Homocysteine levels were statistically significantly lower in elderly participants than in young. Morris MS et al., found that the women of age group 17-54 years had low homocysteine levels and suggested that oestrogen plays an important role in maintenance of low levels of homocysteine (24). In a similar study involving a population of 40-67 years of age; it was found that the homocysteine levels were low even though the vitamin B12 and folic acid status of that population was adequate. The study also states that; generally, homocysteine levels increase with age. Reasons for the higher homocysteine in elderly may be because of changes in renal function. Homocysteine levels may depend on muscle mass, hormone and vitamin status (25). On the other hand; Gharaibeh MY et al., found that levels of hyperhomocysteinemia; low folate and vitamin B12 deficiency is more prevalent in healthy elderly population (26). It has been observed that generally old age is associated with hyperhomocysteinemia and vitamin B12 deficiency; according to many studies. Present study had contrasting findings about homocysteine levels in healthy elderly population. The available data showing similar findings to present study was scarce.
In present study, statistically significantly lower levels of PON1 in elderly participants than in young was found. Cakatay U et al., studied that PON1 is low in the middle aged and elderly population (27). The study suggested that decreased PON1 activity contributes to increased plasma oxidative protein damage in the ageing population. But in some studies it was found significantly higher serum concentrations PON1 in healthy elderly population (28),(29). In present study, vitamin B12 levels were statistically significantly higher in elderly participants than young. According to some recent studies conducted in urban South India as well as Gujarat; significantly high vitamin B12 levels were found in elderly population (30),(31). The correlation of vitamin B12 and homocysteine levels was found to be inverse. More recently, Zhang W et al., studied nutritional status of the elderly population in Rural North China. In contrast to present study findings; they found that severe deficiencies in folate and vitamin B12 levels exist along with hyperhomocysteinemia (32). Folate and vitamin B12 supplementation is necessary to prevent hyperhomocysteinemia.
In present study, statistically significantly higher levels of MDA in elderly participants than in young was found. Akila VP et al., found an increase in MDA levels in the healthy as well as diabetic and hypertensive elderly population (33). Gil P et al., and Inal ME et al., study suggested that old age is associated with an increase in systemic oxidative stress in the form of increased levels of MDA (34),(35). Present study found that cholesterol, HDL and LDL levels were statistically significantly high in elderly participants as compared to young. There was no significant difference in triglycerides and VLDL levels. Some studies from Korea (36) and Sudan (37) found high prevalence of diabetes, hypertension and abnormal concentrations of serum triacylglycerol and total cholesterol, LDL and HDL were in elderly population.
In present study, it was found that the average weight of elderly participants was statistically significantly more than the young. So, also the BMI was statistically significantly more in elderly participants than young. Han TS et al., suggested that obesity is a common and increasing problem because of decreased physical activity and energy expenditure (38). This leads to type II diabetes mellitus, arthritis and depression etc. Obesity in the elderly is potentially preventable and should be tackled carefully. According to BMI, the elderly population was overweight than the young population. In parallel to present study finding; Ganji V and Kafai MR, found that sex, age, BMI, serum folate and serum vitamin B12 are significant predictors of homocysteine concentration (39).
In this study, it was found that the levels of homocysteine in male population of both the groups were statistically significantly higher than the female population. In a study in China as well as two more studies by Lussier-Cocan S et al., and Leowattana W et al., found higher levels of homocysteine in men than women (40),(41),(42). Present study found that increase in the vitamin B12 levels is associated with decrease in the homocysteine levels in both the groups. Wolters M et al., and another studies suggested that the vitamin B12 and folic acid deficiencies are associated with higher homocysteine levels in elderly population (17). The hyperhomocysteinemia is because of lower concentrations of vitamin B12, vitamin B6 and folate (41). This hyperhomocysteinemia can be lowered with the help of supplementation of vitamin B12 and folic acid (43). Brattstrom L et al., stated that age, gender, folate, vitamin B12 and multivitamin usage are all important determinants of the plasma homocysteine concentration (44). Gharaibeh MY et al., suggested that vitamin B12 deficiency in the elderly group along with hyperhomocysteinemia may be due to the high incidence of atrophic gastritis leading to inadequate nutritional intake (26).
Present study did not find any significant correlation of homocysteine with PON1 and MDA in any age group. Cavalca V et al., observed no significant correlation between homocysteine and MDA levels in the patients of coronary artery disease (45). In contrast; a study in the patients of age related macular degeneration found increased homocysteine and MDA and decreased PON1 levels. In this study, it was found that the levels of homocysteine were inversely correlated to levels of TC, HDL and LDL in elderly participants. Present study did not find any correlation of homocysteine with triglycerides and VLDL in any of the age groups. In a study done to correlate the homocysteine levels and lipid profile in elderly patients admitted to Intensive Care Unit (ICU) of the Cardiology Department, it was found that a negative statistical correlation exists between serum homocysteine levels and the concentration of HDL but, not in homocysteine and LDL-C as well as TG (46). Rosolová H et al., found a negative correlation of homocysteine with triglyceride and HDL levels (46). El Oudi M et al., found hyperhomocysteinemia is associated significantly with elevated total cholesterol, LDL cholesterol and lower vitamin B12 levels (47).
It is quite clear that changing dietary habits has been inviting all kinds of serious illnesses to human beings. Cells of younger individuals could lead with normal metabolic pathways though being in compromising scenarios like low vitamin B12 and high homocysteine status. But as age advances, the antioxidant status goes down and cannot stand the damaging mechanisms like lipid peroxidation. The non communicable diseases are slow killers and one is caught at a younger age; the suffering is horrifying. So, younger generations should be made conscious about the preference towards nutritious food which is the only way out.
Limitation(s)
The sample size was too small to establish the exact mechanisms of pathological actions of homocysteine in healthy elderly population. This study was cross-sectional in design. So, development and progression of the diseases in the healthy elderly population; related to homocysteine cannot be observed. Effect of supplementation of vitamin B12 was not done. So, further risk reduction cannot be evaluated. This study should be conducted on a large sample size. Comparison of PON1 and MDA between gender populations was considered as a scope for further research.
Elderly population is not at the risk of developing diseases whose risk factor is homocysteine. Males are at higher risk of development of diseases because of homocysteine than the females of any age group. Homocysteine is not pathogenic in old age even in the presence of other risk factors such as lipid peroxidation, decreased defence mechanisms to lipid peroxidation, raised levels of atherogenic lipids and overweightness. Improvement in the vitamin B12 status can decrease the homocysteine levels.
DOI: 10.7860/JCDR/2023/59242.17653
Date of Submission: Jul 22, 2022
Date of Peer Review: Aug 27, 2022
Date of Acceptance: Dec 24, 2022
Date of Publishing: Mar 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA
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