Effectiveness of integrated approach of yoga therapy versus usual care in management on chronic low back pain patients: A randomized controlled pilot study.

BACKGROUND: Chronic low back pain is associated with both psychological and functional limitation. Yoga therapy has been shown to improve both the aspects. The present study was planned to evaluate integrated approach of yoga therapy with usaul care. AIMS: This controlled randomized trial was done to evaluate the clinical and molecular changes resulting from integrated approach of yoga therapy (IAYT) as an adjunct regimen and compared it with usual care for the management of chronic low back pain patients. MATERIAL AND METHODS: We enrolled 29 adult patients with non-specific chronic low back pain (CLBP). Patients were randomly divided into two groups. The control group received the usual care of treatment as per institutional protocol. The yoga group received IAYT as an adjunct to usual care. Primary outcomes were pain intensity assessed by verbal numerical rating scale (VNRS) and functional ability assessed by Modified Oswestry Disability Index (MODI). Secondary outcomes were pain catastrophizing, quality of life, fear of movement related to CLBP, type of pain, levels of ß-endorphin and TNF-α, and salivary CGRP. All parameters were measured at baseline, 1 and 3 months. RESULTS: A Significant decrease in VNRS score at 1 and 3 months was observed in both the groups with the yoga group showing a more significant reduction in pain over time than the control group (p = 0.036). MODI improved significantly only in the yoga group at 1 and 3 months. Intergroup comparison revealed significantly better MODI over time in the yoga group (p < 0.001). DN4, PDQ, PCS, HADS (anxiety), and Euro QOL had a statistically significant improvement at 1 and 3 months in the yoga group compared with the control group. The HADS (depression) had a statistically significant reduction scores in the yoga group at 3 months compared with the control group (p = 0.012). There was a significant reduction in TNF-α values in the yoga group compared with baseline (p = 0.004). CONCLUSION: IAYT therapy helped in addressing the psychological components of pain and improved quality of life patients with chronic low back pain compared with usual care.

Delivery of gene editing therapeutics.

For the past decades, gene editing demonstrated the potential to attenuate each of the root causes of genetic, infectious, immune, cancerous, and degenerative disorders. More recently, Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 (CRISPR-Cas9) editing proved effective for editing genomic, cancerous, or microbial DNA to limit disease onset or spread. However, the strategies to deliver CRISPR-Cas9 cargos and elicit protective immune responses requires safe delivery to disease targeted cells and tissues. While viral vector-based systems and viral particles demonstrate high efficiency and stable transgene expression, each are limited in their packaging capacities and secondary untoward immune responses. In contrast, the nonviral vector lipid nanoparticles were successfully used for as vaccine and therapeutic deliverables. Herein, we highlight each available gene delivery systems for treating and preventing a broad range of infectious, inflammatory, genetic, and degenerative diseases. STATEMENT OF SIGNIFICANCE: CRISPR-Cas9 gene editing for disease treatment and prevention is an emerging field that can change the outcome of many chronic debilitating disorders.

Tripartite Crosstalk between Cytokine IL-1ß, NMDA-R and Misplaced Mitochondrial Anchor in Neuronal Dendrites is a Novel Pathway for Neurodegeneration in Inflammatory Diseases.

The mitochondrial anchor syntaphilin (SNPH) is a key mitochondrial protein normally expressed in axons to maintain neuronal health by positioning mitochondria along axons for metabolic needs. However, in 2019 we discovered a novel form of excitotoxicity that results when SNPH is misplaced into neuronal dendrites in disease models. A key unanswered question about this SNPH excitotoxicity is the pathologic molecules that trigger misplacement or intrusion of SNPH into dendrites. Here, we identified two different classes of pathologic molecules that interact to trigger dendritic SNPH intrusion. Using primary hippocampal neuronal cultures from mice of either sex, we demonstrated that the pro-inflammatory cytokine IL-1ß interacts with NMDA to trigger SNPH intrusion into dendrites. First, IL-1ß and NMDA each individually triggers dendritic SNPH intrusion. Second, IL-1ß and NMDA do not act independently but interact. Thus, blocking NMDAR by the antagonist MK-801 blocks IL-1ß from triggering dendritic SNPH intrusion. Further, de-coupling the known interaction between IL-1ß and NMDAR by tyrosine inhibitors prevents either IL-1ß or NMDA from triggering dendritic SNPH intrusion. Third, neuronal toxicity caused by IL-1ß or NMDA are strongly ameliorated in SNPH-/- neurons. Taken together, we hypothesize that the known bipartite IL-1ß/NMDAR crosstalk converges to trigger misplacement of SNPH in dendrites as a final common pathway to cause neurodegeneration. Targeting dendritic SNPH in this novel tripartite IL-1ß/NMDAR/SNPH interaction could be a strategic downstream locus for ameliorating neurotoxicity in inflammatory diseases.SIGNIFICANCE STATEMENTThe mitochondrial anchor Syntaphilin (SNPH) is a key mitochondrial protein normally expressed specifically in healthy axons to help position mitochondria along axons to match metabolic needs. In 2019, we discovered that misplacement of SNPH into neuronal dendrites causes a novel form of excitotoxicity in rodent models of multiple sclerosis. A key unanswered question about this new form of dendritic SNPH toxicity concerns pathologic molecules that trigger toxic misplacement of SNPH into dendrites. Here we identified two major categories of pathologic molecules, the pro-inflammatory cytokines and NMDA, that interact and converge to trigger toxic misplacement of SNPH into dendrites. We propose that dendritic mitochondrial anchor provides a novel, single common target for ameliorating diverse inflammatory and excitatory injuries in neurodegenerative diseases.

Ayurvedic Herbal Therapies: A Review of Treatment and Management of Dementia.

Dementia has been characterized by atypical neurological syndromes and several cognitive deficits, such as extended memory loss, strange behavior, unusual thinking, impaired judgment, impotence, and difficulty with daily living activities. Dementia is not a disease, but it is caused by several neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Lewy's bodies. Several drugs and remedies are indicated for alleviating unusual cognitive decline, but no effective pharmacological treatment regimens are available without side effects. Herbal drugs or traditional medicines like Ayurveda have been known for facilitating and corroborating the balance between mind, brain, body, and environment. Ayurvedic therapy comprises 600 herbal formulas, 250 single plant remedies, and natural and holistic health-giving treatments that relieve dementia in patients and increase vitality. Ayurvedic Rasayana herbs [rejuvenating elements] strengthen the brain cells, enhance memory, and decrease stress. The current medicine scenario in the treatment of dementia has prompted the shift in exploring the efficacy of ayurvedic medicine, its safety, and its efficiency. This review presents the literature on several herbal treatments for improving dementia symptomatology and patients' quality of life.

Yoga as a Preventive Intervention for Cardiovascular Diseases and Associated Comorbidities: Open-Label Single Arm Study.

Aim: Common Yoga Protocol (CYP) is a standardized yoga protocol authored by experts from all over the world under the aegis of the Ministry of AYUSH, Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa Rigpa and Homeopathy (AYUSH). The potential of CYP can be determined as a cost-effective lifestyle modification to prevent the risk of developing cardiovascular diseases (CVD). Methods: In this prospective trial, we compared the effect of CYP at baseline and after 1 month. A total of 374 yoga-naïve participants performed CYP under the supervision of experienced trainers. Physiological [body mass index (BMI), blood pressure, percent oxygen saturation], biochemical (fasting blood glucose and lipid profile), and neurocognitive parameters were measured before and after the intervention. Results: At day 30 of yoga practice, serum levels of low-density lipoprotein (LDL), total cholesterol (TC), and high-density lipoprotein (HDL) were found significantly improved as compared to the baseline levels observed at the time of enrollment. Similarly, the lipid profile was also obtained from experienced trainers and found to be significantly different from those of yoga-naïve volunteers. When the intervention was compared between the healthy yoga-naïve participants with yoga-naïve participants suffering from medical issues, it was found that cholesterol profile improved significantly in the healthy-naive group as compared to the diseased group (hypertension, diabetes, underwent surgery, and CVD). Conclusion: These results highlight the need for further research to better understand the effects of yoga on the primary prevention of CVD.

Intrahepatic cholestasis of pregnancy: dilemma in diagnosis and management.

OBJECTIVE: To determine the obstetrical outcomes of women delivered for the diagnosis of intrahepatic cholestasis of pregnancy (ICP). METHODS: Retrospective study of singleton pregnancies diagnosed with ICP between 1 May 2014 and 31 December 2017. Population was analyzed based on bile acids: normal (<10 µmol/L), mild (10 to 40 µmol/L), moderate-severe (>40 µmol/L), and not obtained. Receiver operating characteristic curves established critical values for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) to predict elevated bile acids. Statistical analyses included χ2 for categorical variables and ANOVA for continuous variables. All tests used a 2-sided α level of significance of .05. RESULTS: Bile acids were normal in 39 (45.9%) women, 30 (35.3%) had mild cholestasis, 10 (11.8%) had moderate-severe cholestasis and not obtained for six (7%) women. Gestational diabetes was more common in mild cholestasis (p = .03). There were no differences in demographics, clinical presentation, obstetric interventions and neonatal outcomes. Bile acids took 5-6 days to result. Rate of labor inductions was high in all groups. Postpartum complications occurred in four women in the normal group and in one woman in the mild cholestasis group. Five (12.8%) neonates in the normal group, six (20%) in the mild group, and one (10%) in the severe group were admitted to the NICU. There was no fetal asphyxia, no 5-minute Apgar score <7, and no perinatal deaths. An AST of 27.5 IU/L (p = .002) with sensitivity of 81% and specificity of 76%, and an ALT of 26.7 IU/L (p = .004) with sensitivity of 78% and specificity of 68% predicted elevated bile acids. Improving the sensitivity of AST and ALT to 95%, the ROC curve identified an AST of 62 IU/L with a specificity, positive and negative predictive values of 32, 58 and 86%, respectively; and an ALT of 106 IU/L with a specificity, positive and negative predictive values of 27, 57 and 83%, respectively. CONCLUSIONS: ICP should not be presumed in patients with pruritus. This practice may lead to early term delivery and associated complications.

Potential Biomarkers Associated with Multiple Sclerosis Pathology.

Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves an intricate and aberrant interaction of immune cells leading to inflammation, demyelination, and neurodegeneration. Due to the heterogeneity of clinical subtypes, their diagnosis becomes challenging and the best treatment cannot be easily provided to patients. Biomarkers have been used to simplify the diagnosis and prognosis of MS, as well as to evaluate the results of clinical treatments. In recent years, research on biomarkers has advanced rapidly due to their ability to be easily and promptly measured, their specificity, and their reproducibility. Biomarkers are classified into several categories depending on whether they address personal or predictive susceptibility, diagnosis, prognosis, disease activity, or response to treatment in different clinical courses of MS. The identified members indicate a variety of pathological processes of MS, such as neuroaxonal damage, gliosis, demyelination, progression of disability, and remyelination, among others. The present review analyzes biomarkers in cerebrospinal fluid (CSF) and blood serum, the most promising imaging biomarkers used in clinical practice. Furthermore, it aims to shed light on the criteria and challenges that a biomarker must face to be considered as a standard in daily clinical practice.

Prospective Study of Different Staple Diets of Diabetic Indian Population.

Background: Diabetes is a metabolic disorder characterized by chronic hyperglycemia. Its prevention and regulation depends on dietary pattern and lifestyle. There are numerous studies which have been conducted to elucidate the relationship between type of diet consumption and sugar levels. The objective of this study was to enumerate the distribution of the staple food consumed in seven zones across India and their association with sugar levels. Methods: A pan-India multicentered screening, covering the 63 districts, 29 states, and 4 union territories per populations, was undertaken. A specially designed questionnaire was administered for data collection, which comprised specific questions for diet 17,280 sample was analyzed across seven zones of India. Statistical Package for the Social Sciences (SPSS; 21.0) software was used to analyze the data. Results: The survey suggested that rice and wheat are the major staple food consumed across different regions of India. In Jammu, North, East, South, and central zones, consumption of rice was more than wheat. However, in North and West zones, consumption of wheat was observed to be more than rice. Mean values of fasting blood sugar (FBS), postprandial blood sugar (PPBS) were high in the group consuming Bajra (128.3 & 160.5). Similarly, FBS mean was less in group consuming rice (114.6), and PPBS was low in group consuming ragi (149.2). Conclusion: Staple food has significant effect on FBS, PPBS and glycated haemoglobin cholesterol levels and anthropometric measurements.

Primer for Mainstreaming Mind-Body Techniques for Extreme Climates-Insights and Future Directions.

Background: The deprivation of oxygen reaching the tissues (also termed as hypoxia) affects the normal functioning of the body. This results in development of many diseases like ischemia, glaucoma, MCI (Mild Cognitive Impairment), pulmonary and cerebral edema, stress and depression. There are no effective drugs that can treat such diseases. Despite such failure, alternative interventions such as mind-body techniques (MBTs) have not been adequately investigated. Methods: The first part of this review has been focused on philosophical aspects of various MBTs besides evolving an ayurgenomic perspective. The potential of MBTs as a preventive non-pharmacological intervention in the treatment of various general and hypoxic pathologies has been further described in this section. In the second part, molecular, physiological, and neuroprotective roles of MBTs in normal and hypoxic/ischemic conditions has been discussed. Results: In this respect, the importance of and in vivo studies has also been discussed. Conclusions: Although several studies have investigated the role of protective strategies in coping with the hypoxic environment, the efficacy of MBTs at the molecular level has been ignored.

Depression in High-Risk Type 2 Diabetes Adults.

BACKGROUND: Patients suffering from diabetes mellitus are two to three times more vulnerable to develop depressive symptomatology. PURPOSE: To report the association between depression and high-risk diabetes in India. METHODS: A total of 1,606 adults were recruited for the study. A patient health questionnaire was used to determine the depression on the basis of score. A statistical analysis was done using analysis of covariance (ANCOVA) and binary logistic regression to determine the association between diabetes categories and four degrees of depression. RESULTS: Out of 1,606 participants, 52.6% were males and 47.4% were females, 56.4% belonged to the urban area and 43.6% to the rural area. However, 19.5% (314) had diabetes; 29.1% of diabetes individuals had minimal depression, 38.7% had mild, 17.2% moderate, 12.0% moderately severe, and 3.1% had severe depression. In the self-reported diabetic participant group (N = 142), there was a significantly higher degree of severe depression (3.3%) in the uncontrolled group (HbA1c >7%) as compared to the well-controlled diabetes group (HbA1c <7%). ANCOVA in gender differences in the uncontrolled diabetes group showed that male gender had significantly (P = -.02) higher mean scores of depression. CONCLUSION: This study found that there is a positive association between depression and uncontrolled diabetes in male gender.

Partitioning of radiological, stress and biochemical changes in pre-diabetic women subjected to Diabetic Yoga Protocol.

BACKGROUND: Yoga is an ancient system of wellness with Asana and Pranayama as its most popular and propagated modules for management of lifestyle disorders. OBJECTIVES: The aim of the study was to characterise the liver abnormalities, biochemical changes, and stress levels after Yoga intervention in prediabetic females. MATERIALS AND METHODS: 37 females were randomly divided into Yoga practising and non-practising control groups. The Yoga practising group performed Diabetic Yoga Protocol (DYP) for 3 months. Parameters including size of liver, fatty infiltration, and grade of severity were measured using ultrasonography along with biochemical parameters and stress levels at baseline and after Yoga practice. RESULTS: The glycosylated hemoglobin (HbA1c) and glucose levels were found significantly reduced in prediabetic (p = 0.015) women after practising DYP, although cholesterol levels increased in menopausal women. No escalation of fatty liver was noted among women practising DYP. CONCLUSION: DYP reduced the HbA1c and stress levels and therefore, could be a cost-effective tool for preventing prediabetes to diabetes progression.

Role of Ionizing Radiation in Neurodegenerative Diseases.

Ionizing radiation (IR) from terrestrial sources is continually an unprotected peril to human beings. However, the medical radiation and global radiation background are main contributors to human exposure and causes of radiation sickness. At high-dose exposures acute radiation sickness occurs, whereas chronic effects may persist for a number of years. Radiation can increase many circulatory, age related and neurodegenerative diseases. Neurodegenerative diseases occur a long time after exposure to radiation, as demonstrated in atomic bomb survivors, and are still controversial. This review discuss the role of IR in neurodegenerative diseases and proposes an association between neurodegenerative diseases and exposure to IR.

Disturbed Glucose Metabolism in Rat Neurons Exposed to Cerebrospinal Fluid Obtained from Multiple Sclerosis Subjects.

Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS). In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF) that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO) patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s) expression and suggest that MS appears to be linked with metabolic deformity.

Bioenergetic Failure in Rat Oligodendrocyte Progenitor Cells Treated with Cerebrospinal Fluid Derived from Multiple Sclerosis Patients.

In relapsing-remitting multiple sclerosis (RRMS) subtype, the patient's brain itself is capable of repairing the damage, remyelinating the axon and recovering the neurological function. Cerebrospinal fluid (CSF) is in close proximity with brain parenchyma and contains a host of proteins and other molecules, which influence the cellular physiology, that may balance damage and repair of neurons and glial cells. The purpose of this study was to determine the pathophysiological mechanisms underpinning myelin repair in distinct clinical forms of MS and neuromyelitis optica (NMO) patients by studying the effect of diseased CSF on glucose metabolism and ATP synthesis. A cellular model with primary cultures of oligodendrocyte progenitor cells (OPCs) from rat cerebrum was employed, and cells were treated with CSF from distinct clinical forms of MS, NMO patients and neurological controls. Prior to comprehending mechanisms underlying myelin repair, we determine the best stably expressed reference genes in our experimental condition to accurately normalize our target mRNA transcripts. The GeNorm and NormFinder algorithms showed that mitochondrial ribosomal protein (Mrpl19), hypoxanthine guanine phosphoribosyl transferase (Hprt), microglobulin ß2 (B2m), and transferrin receptor (Tfrc) were identified as the best reference genes in OPCs treated with MS subjects and were used for normalizing gene transcripts. The main findings on microarray gene expression profiling analysis on CSF treated OPCs cells revealed a disturbed carbohydrate metabolism and ATP synthesis in MS and NMO derived CSF treated OPCs. In addition, using STRING program, we investigate whether gene-gene interaction affected the whole network in our experimental conditions. Our findings revealed downregulated expression of genes involved in carbohydrate metabolism, and that glucose metabolism impairment and reduced ATP availability for cellular damage repair clearly differentiate more benign forms from the most aggressive forms and worst prognosis in MS patients.

Hypoxia in CNS Pathologies: Emerging Role of miRNA-Based Neurotherapeutics and Yoga Based Alternative Therapies.

Cellular respiration is a vital process for the existence of life. Any condition that results in deprivation of oxygen (also termed as hypoxia) may eventually lead to deleterious effects on the functioning of tissues. Brain being the highest consumer of oxygen is prone to increased risk of hypoxia-induced neurological insults. This in turn has been associated with many diseases of central nervous system (CNS) such as stroke, Alzheimer's, encephalopathy etc. Although several studies have investigated the pathophysiological mechanisms underlying ischemic/hypoxic CNS diseases, the knowledge about protective therapeutic strategies to ameliorate the affected neuronal cells is meager. This has augmented the need to improve our understanding of the hypoxic and ischemic events occurring in the brain and identify novel and alternate treatment modalities for such insults. MicroRNA (miRNAs), small non-coding RNA molecules, have recently emerged as potential neuroprotective agents as well as targets, under hypoxic conditions. These 18-22 nucleotide long RNA molecules are profusely present in brain and other organs and function as gene regulators by cleaving and silencing the gene expression. In brain, these are known to be involved in neuronal differentiation and plasticity. Therefore, targeting miRNA expression represents a novel therapeutic approach to intercede against hypoxic and ischemic brain injury. In the first part of this review, we will discuss the neurophysiological changes caused as a result of hypoxia, followed by the contribution of hypoxia in the neurodegenerative diseases. Secondly, we will provide recent updates and insights into the roles of miRNA in the regulation of genes in oxygen and glucose deprived brain in association with circadian rhythms and how these can be targeted as neuroprotective agents for CNS injuries. Finally, we will emphasize on alternate breathing or yogic interventions to overcome the hypoxia associated anomalies that could ultimately lead to improvement in cerebral perfusion.

The Molecular Links of Re-Emerging Therapy: A Review of Evidence of Brahmi (Bacopa monniera).

The convolution associated with memory is being resolved with advancement in neuroscience. According to the concurrent assumptions, synaptic plasticity forms one of the basis of memory formation, stabilization and strengthening. In Alzheimer's disease (AD), which is generally characterized by memory dysfunction, connections amongst the cells in the brain are attenuated or lost leading to degeneration of neural networks. Numerous attempts have been made to find new therapies for memory dysfunction with increasing attention and investments being laid on herbal drugs. Many herbal plants and extracts have already documented beneficial results when tested for antiamnesic effects. Brahmi (Bacopa monniera) is one such common herbal drug, which is employed for a long time in the Indian and Chinese medical system in order to treat several disorders. Previous research has shown that Brahmi exerts many pharmacological effects including memory boosting capacity in the treatment of Alzheimer's disease and Schizophrenia, exhibiting antiparkinsonian, antistroke, and anticonvulsant potentials. The present review discusses the chemical constituents of Brahmi along with in vitro and in vivo studies based on the pharmacological effects exerted by it. The efficacy of Brahmi in treating various disorders has evoked sufficient research in recent years and now it is a time to launch multiple clinical trials.

Bypassing hazard of housekeeping genes: their evaluation in rat granule neurons treated with cerebrospinal fluid of multiple sclerosis subjects.

Gene expression studies employing real-time PCR has become an intrinsic part of biomedical research. Appropriate normalization of target gene transcript(s) based on stably expressed housekeeping genes is crucial in individual experimental conditions to obtain accurate results. In multiple sclerosis (MS), several gene expression studies have been undertaken, however, the suitability of housekeeping genes to express stably in this disease is not yet explored. Recent research suggests that their expression level may vary under different experimental conditions. Hence it is indispensible to evaluate their expression stability to accurately normalize target gene transcripts. The present study aims to evaluate the expression stability of seven housekeeping genes in rat granule neurons treated with cerebrospinal fluid of MS patients. The selected reference genes were quantified by real time PCR and their expression stability was assessed using GeNorm and NormFinder algorithms. GeNorm identified transferrin receptor (Tfrc) and microglobulin beta-2 (B2m) the most stable genes followed by ribosomal protein L19 (Rpl19) whereas ß-actin (ActB) and glyceraldehyde-3-phosphate-dehydrogenase (Gapdh) the most fluctuated ones in these neurons. NormFinder identified Tfrc as the best invariable gene followed by B2m and Rpl19. ActB and Gapdh were the least stable genes as analyzed by NormFinder algorithm. Both methods reported Tfrc and B2m the most stably expressed genes and Gapdh the least stable one. Altogether our data demonstrate the significance of pre-validation of housekeeping genes for accurate normalization and indicates Tfrc and B2m as best endogenous controls in MS. ActB and Gapdh are not recommended in gene expression studies related to current one.

Perturbed glucose metabolism: insights into multiple sclerosis pathogenesis.

Multiple sclerosis (MS) is a complex debilitating disease of the central nervous system (CNS) perceived to result from the autoimmune effect of T cells in damaging myelin sheath. However, the exact pathogenesis of the disease remains elusive. Initial studies describing the possibility of defective pyruvate metabolism in MS were performed in 1950s. The group observed elevated blood pyruvate level in both fasting and postprandial times in MS patients with relapse. Similarly, other investigators also reported increased fasting pyruvate level in this disease. These reports hint to a possible abnormality of pyruvate metabolism in MS patients. In addition, increase in levels of Krebs cycle acids like alpha-ketoglutarate in fasting and citrate after glucose intake in MS patients further strengthened the connection of disturbed pyruvate metabolism with MS progression. These studies led the investigators to explore the role of disturbed glucose metabolism in pathophysiological brain function. Under normal circumstances, complex molecules are metabolized into simpler molecules through their respective pathways. Differential expression of genes encoding enzymes of the glucose metabolic pathway in CNS may result in neurological deficits. In this review article, we discuss the studies related to disturbed carbohydrate metabolism in MS and other neurodegenerative diseases. These observations open new perspectives for the understanding of metabolic dynamics in MS yet many puzzling aspects and critical questions need to be addressed. Much more research is required to fully unravel the disease mechanism, and a proper understanding of the disease could eventually lead to new treatments.

Vascular endothelial growth factor and monocyte chemoattractant protein-1 levels unaltered in symptomatic atherosclerotic carotid plaque patients from north India.

We aimed to identify the role of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP-1) as a serum biomarker of symptomatic carotid atherosclerotic plaque in North Indian population. Individuals with symptomatic carotid atherosclerotic plaque have high risk of ischemic stroke. Previous studies from western countries have shown an association between VEGF and MCP-1 levels and the incidence of ischemic stroke. In this study, venous blood from 110 human subjects was collected, 57 blood samples of which were obtained from patients with carotid plaques, 38 neurological controls without carotid plaques, and another 15 healthy controls who had no history of serious illness. Serum VEGF and MCP-1 levels were measured using commercially available enzyme-linked immunosorbent assay. We also correlated the data clinically and carried out risk factor analysis based on the detailed questionnaire obtained from each patient. For risk factor analysis, a total of 70 symptomatic carotid plaque cases and equal number of age and sex matched healthy controls were analyzed. We found that serum VEGF levels in carotid plaque patients did not show any significant change when compared to either of the controls. Similarly, there was no significant upregulation of MCP-1 in the serum of these patients. The risk factor analysis revealed that hypertension, diabetes, and physical inactivity were the main correlates of carotid atherosclerosis (p < 0.05). Prevalence of patients was higher residing in urban areas as compared to rural region. We also found that patients coming from mountain region were relatively less vulnerable to cerebral atherosclerosis as compared to the ones residing at non mountain region. On the contrary, smoking, obesity, dyslipidemia, alcohol consumption, and tobacco chewing were not observed as the determinants of carotid atherosclerosis risk in North India (p > 0.05). We conclude that the pathogenesis of carotid plaques may progress independent of these inflammatory molecules. In parallel, risk factor analysis indicates hypertension, diabetes, and sedentary lifestyle as the most significant risk factors of ischemic stroke identified in North India. This could be helpful in early identification of subjects at risk for stroke and devising health care strategies.