Current Scenario of Clinical Diagnosis to Identify Inborn Errors of Metabolism with Precision Profiling for Expanded Screening in Infancy in a Resource-limited Setting.

Inborn errors of metabolism (IEM) are a diverse collection of abnormalities that cause a variety of morbidities and mortality in children and are classified as uncommon genetic diseases. Early and accurate detection of the condition can save a patient's life. By aiding families as they navigate the experience of having a child with an IEM, healthcare practitioners have the chance to reduce the burden of negative emotional consequences. New therapeutic techniques, such as enzyme replacement and small chemical therapies, organ transplantation, and cellular and gene-based therapies using whole-genome sequencing, have become available in addition to traditional medical intake and cofactor treatments. In the realm of metabolic medicine and metabolomics, the twentyfirst century is an exciting time to be alive. The availability of metabolomics and genomic analysis has led to the identification of a slew of novel diseases. Due to the rarity of individual illnesses, obtaining high-quality data for these treatments in clinical trials and real-world settings has proven difficult. Guidelines produced using standardized techniques have helped enhance treatment delivery and clinical outcomes over time. This article gives a comprehensive description of IEM and how to diagnose it in patients who have developed clinical signs early or late. The appropriate use of standard laboratory outcomes in the preliminary patient assessment is also emphasized that can aid in the ordering of specific laboratory tests to confirm a suspected diagnosis, in addition, to begin treatment as soon as possible in a resource limiting setting where genomic analysis or newborn screening facility is not available.

Deficiency of folate and vitamin B12 increases oxidative stress in chronic pancreatitis patients.

BACKGROUND: Folate and vitamin B12 are involved in metabolic reactions for combating oxidative stress. We measured erythrocyte folate and plasma vitamin B12 and compared these with blood antioxidants - erythrocyte glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and plasma vitamin C - and marker of lipid peroxidation, thiobarbituric acid reactive substance (TBARS), in chronic pancreatitis (CP) patients. METHODS: One hundred and seventy-five CP patients (91 tropical, 84 alcoholic) and 113 healthy controls were recruited. Erythrocyte folate and plasma vitamin B12 were measured using microbiological assay, and antioxidant levels and erythrocyte TBARS by spectrophotometry. RESULTS: Erythrocyte folate and plasma vitamin B12 were significantly lower in CP patients than controls (225.4 ± 9.13 vs. 380.38 ± 17.29 nmol/L, p < 0.001 and 233.23 ± 10.4 vs. 338.84 ± 19.01 pmol/L, p < 0.001), and in diabetic- vs. non-diabetic CP patients. Blood antioxidant levels were significantly lower and TBARS was higher in CP patients as compared to controls. Low folate level correlated with low GSH levels (r = 0.314, p < 0.001). CP patients with low folate and vitamin B12 had low GSH and GPx levels as compared to patients with normal folate and vitamin B12 levels. Low vitamin B12 level was associated with 3.24 (95% CI 1.11-9.46, p < 0.05) fold increased risk of pancreatic insufficiency. Smoking was associated with 9.82 (95% confidence interval [CI] 3.3-29.22, p < 0.05) fold increased risk of having low folate levels. CONCLUSION: Low folate and vitamin B12 levels were associated with increased oxidative stress in CP patients.

Nanomedicine in the Diagnosis and Treatment of Atherosclerosis-A Systematic Review.

BACKGROUND: Atherosclerosis is a chronic inflammatory condition causing very high morbidity and mortality. It is characterized by accumulation of plaques within arteries. Nanomedicine is an emerging field of medicine utilizing nanotechnology for advanced imaging and therapy. Nanomedicine has led to significant developments in the field of cardiovascular diseases, including atherosclerosis. Many nanoformulations have been developed with anti-atherosclerotic effects. Nanomedicine tools have been used in the imaging of atherosclerosis. Various nanocarriers have been employed for successful localization in atherosclerotic lesions. The biggest challenge for such delivery vehicles has been localization to atherosclerosis lesions. Several strategies have been employed to overcome these defects. Strategies have also been developed for stabilization of atherosclerotic lesions. CONCLUSION: Nanotechnology is also an important tool for the development of novel biomarkers. At the same time there are also potential limitations. Toxicity, lack of translation from preclinical phase to clinical development, and the inability to address the chronic phase of atherosclerosis are the most important among them. Future toxicity studies shall enlighten us further on this exciting research area.

Attitude of bachelor of dental surgery students and interns toward teaching-learning process in Government Dental College, Kottayam, Kerala, India.

INTRODUCTION: The educational environment affects the academic performance of students. One of the most widely utilized tools for measuring the educational environment is Dundee Ready Education Environment Measure (DREEM). The objective of the study was to assess the attitude toward study environment, as measured using DREEM questionnaire, and to find out the differences in perception of various batches of dental students. MATERIALS AND METHODS: All Bachelor of Dental Surgery students from Government Dental College, Kottayam, Kerala, India, were included in the study. They were given the well-established DREEM questionnaire. A total of 234 students took part in the study, belonging to 2009, 2010, 2011, 2012, 2013, and 2014 batches. DREEM subcategories were analyzed for significance using analysis of variance. The significance of DREEM score across the different batches was further analyzed using post hoc test. RESULTS: Overall, DREEM score was positive (111.14), but there is need for improvement. Individual questions also were given positive score for most questions. The maximum score was obtained for 3rd year students. Similar results are obtained for three of the five subcategories of DREEM. CONCLUSION: The total DREEM score was positive (111.14). The total score as well as the scores for the subcategories was highest in 3rd year dental students. The increase might be due to the excitement of clinical exposure for the first time in 3rd year students.

A randomized study of coconut oil versus sunflower oil on cardiovascular risk factors in patients with stable coronary heart disease.

BACKGROUND AND RATIONALE: Coronary artery disease (CAD) and its pathological atherosclerotic process are closely related to lipids. Lipids levels are in turn influenced by dietary oils and fats. Saturated fatty acids increase the risk for atherosclerosis by increasing the cholesterol level. This study was conducted to investigate the impact of cooking oil media (coconut oil and sunflower oil) on lipid profile, antioxidant mechanism, and endothelial function in patients with established CAD. DESIGN AND METHODS: In a single center randomized study in India, patients with stable CAD on standard medical care were assigned to receive coconut oil (Group I) or sunflower oil (Group II) as cooking media for 2 years. Anthropometric measurements, serum, lipids, Lipoprotein a, apo B/A-1 ratio, antioxidants, flow-mediated vasodilation, and cardiovascular events were assessed at 3 months, 6 months, 1 year, and 2 years. RESULTS: Hundred patients in each arm completed 2 years with 98% follow-up. There was no statistically significant difference in the anthropometric, biochemical, vascular function, and in cardiovascular events after 2 years. CONCLUSION: Coconut oil even though rich in saturated fatty acids in comparison to sunflower oil when used as cooking oil media over a period of 2 years did not change the lipid-related cardiovascular risk factors and events in those receiving standard medical care.

Alterations in the levels of plasma amino acids in polycystic ovary syndrome--A pilot study.

BACKGROUND & OBJECTIVES: Plasma amino acid levels are known to be altered in conditions like sepsis and burns which are situations of metabolic stress. Polycystic ovary syndrome (PCOS), a condition which affects a woman throughout her life, is said to be associated with metabolic stress. This study was undertaken to assess if there were significant alterations in the levels of plasma amino acids in women with PCOS. METHODS: Sixty five women with PCOS along with the similar number of age matched normal controls were included in this study. Levels of 14 amino acids were determined using reverse phase high performance liquid chromatography. RESULTS: The levels of methionine, cystine, isoleucine, phenylalanine, valine, tyrosine, proline, glycine, lysine and histidine were found to be significantly (P<0.001) lower in cases than in controls. Arginine and alanine levels were found to be significantly (P<0.001) higher in cases compared with controls. INTERPRETATION & CONCLUSIONS: Our findings showed significant derangement in the levels of plasma amino acids in women with PCOS which might be due to the oxidative and metabolic stress associated with it. Further studies need to be done to confirm the findings.

Urinary proteomics and metabolomics in the diagnosis of pediatric disorders.

Proteomics is the study of structures and functions of proteins, while metabolomics is the study of small-molecule metabolites in the cells, tissues, and organs of the organism. Proteomic technologies have wide applications in medical field. The current revolution in proteomics has led to the discovery of several new protein markers for various disorders. Urinary proteomics and metabolomics have also evolved in the recent years, for the diagnosis of both renal and nonrenal disorders. The urinary proteome varies in normal and abnormal conditions. Different techniques are employed for the analysis of pediatric urinary proteome, the commonest being MS. Before introduction into clinical use, there is the need for careful standardization. Available data suggest that there are differences in urinary proteome between adult and pediatric populations. It is noted that infant urine contains proteins involved in translation and transcription, cellular growth, and metabolic processes, which are not predominant in adult urine. Available data on urinary proteomic and metabolomic profile in common pediatric disorders are also reviewed here.

Diet, nutrient deficiency and chronic pancreatitis.

The aetiopathogenesis of chronic pancreatitis (CP) appears to be multifactorial with interplay of genetic and environmental factors such as alcohol, smoking and diet. Dietary factors in the form of a fat- and protein-rich diet are important cofactors in the aetiopathogenesis of alcoholic pancreatitis. Malnutrition used to be a hallmark in tropical pancreatitis. Presently, it appears that malnutrition is an effect rather than a causative factor for tropical pancreatitis; however, micronutrient deficiency could possibly be implicated in the aetiopathogenesis. The role of dietary toxins such as cassava is no longer considered an important risk factor; however, these patients are at a higher risk for defective detoxification of cyanogens. Decrease in levels of sulphur amino acids (SAAs), folate and zinc have been reported. Oxidative stress and antioxidant depletion are key pathogenetic mechanisms. The role of antioxidants in pain relief is an area of interest. Supplementation of fat-soluble vitamins and micronutrients is a cornerstone in medical management. Folate and zinc supplementation may be beneficial and is a focus of ongoing research. In the future, prophylaxis for CP by a daily micronutrient tablet among high-risk groups in endemic areas could prove to be a potentially important public health measure. However, further studies are required.

Composition of plasma and atheromatous plaque among coronary artery disease subjects consuming coconut oil or sunflower oil as the cooking medium.

OBJECTIVES: Coconut oil, which is rich in medium-chain saturated fatty acids, is the principal cooking medium of the people of Kerala, India. Replacement of saturated fat with polyunsaturated fat is effective in reducing serum cholesterol levels. However, the effect of substituting coconut oil with sunflower oil on the fatty acid composition of plaque has not been thoroughly investigated. We therefore evaluated and compared the fatty acid composition of plasma and plaque among subjects consuming coconut oil or sunflower oil as the cooking medium. METHODS: Endarterectomy samples and plasma samples were obtained from subjects who underwent coronary artery bypass grafts (n = 71). The subjects were grouped based on the type of oil they were using as their cooking medium (coconut oil or sunflower oil). The fatty acid composition in the plaques and the plasma was determined by HPLC and the data were analyzed statistically. RESULTS: Sunflower oil consumers had elevated concentrations of linoleic acid (p = 0.001) in plasma, while coconut oil users had higher myristic acid levels (p = 0.011) in plasma. Medium-chain fatty acids did not differ significantly between the two groups in the plasma. Medium-chain fatty acids were detected in the plaques in both groups of subjects. In contrast to previous reports, long-chain saturated fatty acids dominated the lipid content of plaque in this population, and the fatty acid composition of plaque was not significantly different between the two groups. No correlation between fatty acids of plasma and plaque was observed in either group. CONCLUSION: A change in cooking medium, although it altered the plasma fatty acid composition, was not reflected in the plaque composition.

Organ Specific Tumor Markers: What's New?

Tumor markers are molecules produced in the body in response to cancer. An ideal tumor marker should have high sensitivity and specificity, should be cheap, and should be easily detected in body fluids. Identification of novel markers is important and it is expected that with the advent of newer technologies, more reliable markers will be discovered. This review discusses the currently available tumor markers for different malignancies.

Assessment of cassava toxicity in patients with tropical chronic pancreatitis.

BACKGROUND AND AIM: There have been conflicting reports on the role of cassava ingestion in tropical pancreatitis (TCP). In this study we aimed to estimate cyanogens detoxifying enzyme rhodanese, thiocyanate and sulfur containing amino acids in cassava consumer as well as cassava non-consumer TCP patients and healthy controls and compare the same. METHODS: Eighty-six TCP patients and 90 healthy controls were recruited. Serum rhodanese, thiocyanate, plasma amino acids, urinary inorganic sulfate/creatinine were measured. RESULTS: There was significant reduction in serum rhodanese activity in both cassava consumer- and non-consumer TCP patients as compared to controls but no significant difference between cassava consumer- and non-consumer TCP patients was observed. Serum thiocyanate was significantly lower in cassava consumer TCP patients as compared to cassava consumer controls but not significantly different from cassava non-consumer TCP patients. Plasma methionine, cysteine and urinary inorganic sulfate / creatinine ratio was significantly lower in both cassava consumer and non-consumer TCP patients as compared to controls but were comparable among cassava consumers and non-consumers. CONCLUSIONS: Significant reduction in rhodanese activity with concomitant decrease in sulfur containing amino acids and antioxidants such as glutathione suggests that TCP patients are at higher risk of defective detoxification of cyanogens. However there was no difference between cassava consumers and non-consumers. Low levels of sulfur amino acids may contribute to the development of pancreatitis.

Assessment of oxidative status in chronic pancreatitis and its relation with zinc status.

BACKGROUND: Oxidative stress-induced free radicals have been implicated in the pathology of chronic pancreatitis (CP). AIM: We aimed to estimate oxidative stress and antioxidant status in tropical chronic pancreatitis (TCP) and alcoholic chronic pancreatitis (ACP) and correlate with zinc status. METHODS: One hundred and seventy-five CP patients (91 TCP, 84 ACP) and 113 healthy subjects were prospectively studied. Disease characteristics and imaging features were recorded. Erythrocyte reduced glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), plasma vitamin C, and erythrocyte thiobarbituric acid reactive substance (TBARS) were estimated by spectrophotometry. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. RESULTS: Enhanced lipid peroxidation with concomitant decrease in antioxidant status was observed in both TCP and ACP patients (p < 0.05). The findings were comparable in both diabetic and non-diabetic CP patients. Significantly, lower plasma vitamin C and elevated levels of erythrocyte TBARS was noted in TCP as compared to ACP patients. The erythrocyte zinc significantly correlated with SOD activity (r = 0.450, p < 0.001). CONCLUSIONS: Our study corroborates the role of oxidative stress in CP and suggests some differences in oxidative status in TCP and ACP patients. Zinc deficiency appears to affect oxidative status in CP patients.

Impact of integrated amrita meditation technique on adrenaline and cortisol levels in healthy volunteers.

THE OBJECTIVE WAS TO FIND OUT THE EFFECT OF INTEGRATED AMRITA MEDITATION TECHNIQUE (IAM) ON THE STRESS HORMONES: adrenaline and cortisol. One hundred and fifty healthy subjects were randomized into three groups. Blood was collected at 0 hour, 48 hours, 2 months, and 8 months after the first visit. Adrenaline was analyzed by ELISA and cortisol by Chemiluminescent method. In the IAM, PMR and control groups 44, 44, and 36 came, respectively, for the baseline visit. Within group, cortisol and adrenaline levels reduced in the IAM 48 hours onwards and the fall sustained until 8 months (P < .05). ANCOVA (Repeated measures) on adrenaline taking the four levels of observation showed a highly significant (P = .001) drop in the IAM group. The mean cortisol values between groups were not statistically significant (P = .138). IAM Technique was effective in reducing adrenaline and cortisol levels within group comparisons.

Alterations in plasma amino acid levels in chronic pancreatitis.

CONTEXT: Dietary proteins and amino acids can modulate pancreatic function. OBJECTIVE: Our aim was to estimate the levels of plasma amino acids in chronic pancreatitis patients and study their relationship with disease characteristics as well as exocrine and endocrine insufficiency. PATIENTS: One hundred and seventy-five consecutive adult patients with chronic pancreatitis: 84 patients with alcoholic chronic pancreatitis and 91 patients with tropical chronic pancreatitis. One hundred and thirteen healthy controls were also studied. DESIGN: Prospective study. MAIN OUTCOME MEASURES: Disease characteristics and imaging features were recorded. Plasma-free amino acid levels were estimated using reverse-phase high-performance liquid chromatography. Polyclonal antibody ELISA was used to assess pancreatic fecal elastase-1. RESULTS: The majority of the plasma free amino acid levels decreased in chronic pancreatitis patients whereas glutamate, glycine, proline and lysine were elevated as compared to the controls. Multivariate logistic regression analysis revealed that the decrease in branched chain amino acid concentration was significantly associated with the presence of diabetes and low fecal elastase-1. In addition, a significant positive correlation was observed between branched chain amino acids and pancreatic elastase-1 (rs=0.724, P<0.001). CONCLUSION: Reductions of plasma amino acid levels are seen in chronic pancreatitis, particularly sulphur containing amino acids and branched chain amino acids. Selective amino acid deficiencies seem to correlate with exocrine and endocrine insufficiency.

Organic acidurias: an updated review.

Organic acidurias are an important class of inherited metabolic disorders arising due to defect in intermediary metabolic pathways of carbohydrate, amino acids and fatty acid oxidation. This review summarizes the current knowledge about the important organic acidurias in the Indian population. Specifically, diagnosis and principles of treatment of organic acidurias are covered. The salient features of common organic acidurias as well as their prevalence in various parts of the world are reviewed in some detail.

Chronic pancreatitis is associated with hyperhomocysteinemia and derangements in transsulfuration and transmethylation pathways.

OBJECTIVES: Homocysteine has been implicated in vascular dysfunction and thrombosis, as well as inflammatory conditions. This study was aimed to find out whether chronic pancreatitis (CP) is associated with hyperhomocysteinemia and derangements of transmethylation and transsulfuration pathways. METHODS: We estimated homocysteine and its metabolites in 45 alcoholic CP patients, 45 tropical CP patients, and 48 healthy controls. RESULTS: Significant increases in plasma total homocysteine and decreases in red blood cell folate, reduced glutathione, plasma methionine, cysteine, and urinary inorganic sulfate/creatinine ratio were observed in both alcoholic and tropical CP patients in comparison with healthy controls. Red blood cell glutathione and plasma cysteine levels were significantly lower in alcoholic than in tropical CP patients. However, plasma vitamin B12 levels were comparable between CP patients and controls. No significant differences in these parameters were observed between diabetic patients and nondiabetic patients. Multivariate regression analysis showed a significant negative correlation between homocysteine and folate (r = -0.415, P = 0.001) and a positive correlation between glutathione and cysteine levels (r = 0.37, P = 0.003). CONCLUSIONS: Chronic pancreatitis is associated with hyperhomocysteinemia and derangements in transmethylation and transsulfuration pathways. Low folate levels observed in these patients seem to have a key role in this derangement.

Zinc status in chronic pancreatitis and its relationship with exocrine and endocrine insufficiency.

CONTEXT: A major role of the pancreas in zinc homeostasis has been suggested. OBJECTIVE: To assess erythrocyte zinc status in chronic pancreatitis and to correlate it with pancreatic exocrine and endocrine insufficiency. PATIENTS: One hundred and one patients with chronic pancreatitis (34 alcoholic chronic pancreatitis, 67 tropical chronic pancreatitis) were prospectively studied. MAIN OUTCOME MEASURE: Disease characteristics and imaging features were recorded. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. Exocrine insufficiency was assessed using polyclonal antibody ELISA for pancreatic stool elastase1. Endocrine insufficiency was assessed by serum glucose levels and insulin requirement. RESULTS: Erythrocyte zinc was significantly lower in chronic pancreatitis patients than in the controls (26.5+/-9.5 microg/g Hb vs. 38.0+/-6.6 microg/g Hb; P<0.001), and in tropical chronic pancreatitis than in alcoholic chronic pancreatitis (25.0+/-10.4 microg/g Hb vs. 29.6+/-6.5 microg/g Hb, P=0.001). In chronic pancreatitis patients who had exocrine insufficiency, erythrocyte zinc positively correlated with stool elastase1 (r=0.587, P<0.001). Erythrocyte zinc levels were significantly lower in diabetic patients as compared to non-diabetics (P=0.036). CONCLUSIONS: This study demonstrates zinc deficiency in chronic pancreatitis patients, and that zinc deficiency correlates with exocrine and endocrine insufficiency. Further studies may clarify the possible benefits of zinc supplementation in chronic pancreatitis.

BRCA1 and BRCA2 germline mutation analysis among Indian women from south India: identification of four novel mutations and high-frequency occurrence of 185delAG mutation.

Mutations in the BRCA1 and BRCA2 genes profoundly increase the risk of developing breast and/or ovarian cancer among women. To explore the contribution of BRCA1 and BRCA2 mutations in the development of hereditary breast cancer among Indian women, we carried out mutation analysis of the BRCA1 and BRCA2 genes in 61 breast or ovarian cancer patients from south India with a positive family history of breast and/or ovarian cancer. Mutation analysis was carried out using conformation-sensitive gel electrophoresis (CSGE) followed by sequencing. Mutations were identified in 17 patients (28.0%); 15 (24.6%) had BRCA1 mutations and two (3.28%) had BRCA2 mutations. While no specific association between BRCA1 or BRCA2 mutations with cancer type was seen, mutations were more often seen in families with ovarian cancer. While 40% (4/10) and 30.8% (4/12) of families with ovarian or breast and ovarian cancer had mutations, only 23.1% (9/39) of families with breast cancer carried mutations in the BRCA1 and BRCA2 genes. In addition, while BRCA1 mutations were found in all age groups, BRCA2 mutations were found only in the age group of < or =40 years. Of the BRCA1 mutations, there were three novel mutations (295delCA; 4213T-->A; 5267T-->G) and three mutations that have been reported earlier. Interestingly, 185delAG, a BRCA1 mutation which occurs at a very high frequency in Ashkenazi Jews, was found at a frequency of 16.4% (10/61). There was one novel mutation (4866insT) and one reported mutation in BRCA2. Thus, our study emphasizes the importance of mutation screening in familial breast and/or ovarian cancers, and the potential implications of these findings in genetic counselling and preventive therapy.