Cholesterol Homeostasis, Mechanisms of Molecular Pathways, and Cardiac Health: A Current Outlook.

The metabolism of lipoproteins, which regulate the transit of the lipid to and from tissues, is crucial to maintaining cholesterol homeostasis. Cardiac remodeling is referred to as a set of molecular, cellular, and interstitial changes that, following injury, affect the size, shape, function, mass, and geometry of the heart. Acetyl coenzyme A (acetyl CoA), which can be made from glucose, amino acids, or fatty acids, is the precursor for the synthesis of cholesterol. In this article, the authors explain concepts behind cardiac remodeling, its clinical ramifications, and the pathophysiological roles played by numerous various components, such as cell death, neurohormonal activation, oxidative stress, contractile proteins, energy metabolism, collagen, calcium transport, inflammation, and geometry. The levels of cholesterol are traditionally regulated by 2 biological mechanisms at the transcriptional stage. First, the SREBP transcription factor family regulates the transcription of crucial rate-limiting cholesterogenic and lipogenic proteins, which in turn limits cholesterol production. Immune cells become activated, differentiated, and divided, during an immune response with the objective of eradicating the danger signal. In addition to creating ATP, which is used as energy, this process relies on metabolic reprogramming of both catabolic and anabolic pathways to create metabolites that play a crucial role in regulating the response. Because of changes in signal transduction, malfunction of the sarcoplasmic reticulum and sarcolemma, impairment of calcium handling, increases in cardiac fibrosis, and progressive loss of cardiomyocytes, oxidative stress appears to be the primary mechanism that causes the transition from cardiac hypertrophy to heart failure. De novo cholesterol production, intestinal cholesterol absorption, and biliary cholesterol output are consequently crucial processes in cholesterol homeostasis. In the article's final section, the pharmacological management of cardiac remodeling is explored. The route of treatment is explained in different steps: including, promising, and potential strategies. This chapter offers a brief overview of the history of the study of cholesterol absorption as well as the different potential therapeutic targets.

Effect of Valproate Monotherapy on Thyroid Function Tests and Magnesium Levels in Children With Epilepsy.

BACKGROUND: Antiseizure drug valproate alters thyroid functions. Magnesium is implicated in the pathogenesis of epilepsy and it may affect the efficacy of valproate and thyroid functions. OBJECTIVE: To study the effect of six months of valproate monotherapy on thyroid functions and serum magnesium levels. To study the association among these levels and the effects of clinicodemographic profile. MATERIALS AND METHOD: Children aged three to 12 years presenting with newly diagnosed epilepsy were enrolled. A venous blood sample was collected for estimation of thyroid function test (TFT), magnesium, and valproate levels at onset and after six months of valproate monotherapy. Valproate levels and TFT were analyzed by chemiluminescence and magnesium by colorimetric method. RESULTS: Thyroid stimulating hormone (TSH) increased significantly from 2.14±1.64 µIU/ml at enrollment to 3.64±2.15 µIU/ml at six months (p<0.001), free thyroxine (FT4) decreased significantly (p<0.001). Serum magnesium (Mg) decreased from 2.30±0.29 mg/dl to 1.94±0.28 mg/dl (p<0.001). At six months, eight out of 45 (17.77%) participants had significantly increased mean TSH levels (p=0.008). Serum valproate levels were not associated significantly with TFT and Mg (p<0.05). There was no effect of age, sex, or repeat seizures on the measured parameters. CONCLUSION: The TFT and Mg levels are altered by six months of valproate monotherapy in children with epilepsy. Hence we suggest monitoring and supplementation if required.

Evaluation of Gamma Radiation-Induced Biochemical Changes in Skin for Dose Assesment: A Study on Small Experimental Animals.

OBJECTIVE: Researchers have been evaluating several approaches to assess acute radiation injury/toxicity markers owing to radiation exposure. Keeping in mind this background, we assumed that whole-body irradiation in single fraction in graded doses can affect the antioxidant profile in skin that could be used as an acute radiation injury/toxicity marker. METHODS: Sprague-Dawley rats were treated with CO-60 gamma radiation (dose: 1-5 Gy; dose rate: 0.85 Gy/minute). Skin samples were collected (before and after radiation up to 72 hours) and analyzed for glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPx). RESULTS: Intra-group comparison showed significant differences in GSH, GPx, SOD, and CAT, and they declined in a dose-dependent manner from 1 to 5 Gy (P value0.05). CONCLUSIONS: This study suggests that skin antioxidants were sensitive toward radiation even at a low radiation dose, which can be used as a predictor of radiation injury and altered in a dose-dependent manner. These biochemical parameters may have wider application in the evaluation of radiation-induced skin injury and dose assessment. (Disaster Med Public Health Preparedness. 2019;13:197-202).

Prospective Analytical Controlled Study Evaluating Serum Biotin, Vitamin B12, and Folic Acid in Patients with Premature Canities.

BACKGROUND: Premature canities is a common yet unfathomed disorder. The evidence for the role of micronutrient deficiency in premature canities is not well established. AIM: The present study was undertaken to evaluate the micronutrient levels in Indian patients with premature canities as compared to controls. MATERIALS AND METHODS: We conducted a case-control study in 52 self-reporting patients with premature canities (<20 years age). Micronutrient levels including serum Vitamin B12, biotin, and folic acid were assessed and compared among the patients and controls. RESULTS: We observed that mean serum Vitamin B12 (198.07 ± 88.98 pg/ml in cases vs. 343.07 ± 143.06 pg/ml in controls, P = 0.000), folic acid (6.22 ± 2.46 ng/ml in cases vs. 8.49 ± 4.18 ng/ml in controls, P = 0.01), and biotin (252.71 ± 18.79 pg/ml in cases vs. 266.47 ± 30.44 pg/ml in controls, P = 0.013) levels were significantly lower in cases as compared to the controls. CONCLUSION: In view of the dark hair and many prevailing myths, premature canities is a significant problem in Asians with profound psychosocial impact. This study unveils the association with Vitamin B12, folic acid, and biotin deficiencies. Larger studies are recommended to arrive on a logical conclusion.

Profile of Indian patients with premature canities.

BACKGROUND: Premature canities is a common yet incompletely understood dermatological entity with scarce demographic and clinical data. AIM: Evaluation of the demographic and clinical profile of cases with premature canities and to look for systemic associations. METHODS: Fifty two self-reported cases of premature canities (onset before 20 years of age) and an equal number of healthy controls were recruited from the outpatient department of the Department of Dermatology, Guru Teg Bahadur Hospital Delhi, India from November 2011 to March 2013. A detailed history including onset, duration and pattern of involvement, a family history with pedigree charting and scalp examination were recorded on a predesigned proforma. A history of atopy was looked for in all study subjects and they were screened for thyroid disorder and diabetes. RESULTS: The mean age of cases and controls was comparable. The mean age of onset of graying was 11.6 ± 3.6 years. The mean duration at the time of presentation was 39.8 ± 37.2 months. The frontal region was the earliest affected area in 25 (48.1%) cases. Positive family history of premature canities was reported in 39 (75%) cases with an equal prevalence on paternal and maternal sides. More than half of the cases, 29 (55.8%) reported having a first degree relative affected by premature canities, 13 (25%) had a second degree and 20 (38.5%) had a third degree relative affected. Atopy was found to be strongly associated with premature canities with an odds ratio of 3.8. No association with thyroid abnormality or diabetes mellitus was seen. LIMITATION: The study suffered from the limitation of a small sample size. CONCLUSION: It was observed that the process of graying mostly starts in the frontal region. It was also found to be associated with a strong family history and atopic predisposition. Larger studies are recommended to arrive at a definite conclusion.

Multiple parametric approaches to assess acute radiation lung injury of rats radiation lung injury of rats.

The effect of whole body gamma irradiation (WBI) in single fraction was studied, as well as its influence on the secretion of various biochemical markers and cellular component that could be used as acute radiation lung injury marker. Sprague dawley rats were treated with WBI (60Co) of radiation dose from 1 Gy to 5 Gy (dose rate - 0.95 Gy/min). Bronchoalveolar lavage fluid was retrieved from all animals in control and radiation treated groups up to 72 h post radiation. Bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH ), acid phosphatase (AP ), alkaline phosphatase (ALP ), cell count and total protein. Intragroup and intergroup comparison of BALF parameters at different radiation doses showed significant difference. LDH was significantly increased as the dose increased from 1Gy to 5Gy (P = 0.00) after 2 h with effect size of difference (r > 0.3). ALP was significantly altered after 3Gy and 4Gy (P < 0.05). AP was significantly altered at 2Gy-5Gy (p < 0.05). Total protein level changed significantly from 1Gy to 5Gy (P < 0.00). Cellular content of BALF showed significant changes after radiation exposure. BALF parameters like LDH, AP, ALP, neutrophils, lymphocytes, total leukocyte count and total protein were sensitive to radiation exposure and their levels vary significantly up to 72 h after single whole body radiation exposure in Sprague dawley rats. It can be concluded that the biochemical indices in BALF have more wide application in evaluation of acute radiation induced lung injury.

Assessment of Oxidative Stress in Patients with Premature Canities.

CONTEXT: Premature canities is a common, yet unexplored disorder. Oxidative stress levels have been evaluated within the greying hair follicle but not in the sera of patients with premature canities. AIMS: To evaluate the oxidative stress parameters in the sera of patients with premature canities. SETTINGS AND DESIGN: A pilot case-controlled study, conducted in a tertiary care setup in Delhi during November 2011 to December 2012. MATERIALS AND METHODS: Fifty-two self-reporting cases of premature canities (age of onset <20 years) and 30 healthy controls were recruited from outpatient Department of Dermatology. Oxidative stress parameters (serum malonaldehyde (MDA), whole blood reduced glutathione (rGSH) and serum ferric reducing antioxidant potential [FRAP]) were assessed in cases and controls. Mann-Whitney test was used to compare the oxidative stress parameters between the two groups (SPSS version 17.0, SPSS Inc, Chicago, USA; P < 0.05 considered as significant). RESULTS: The age and sex distribution of cases and controls was comparable. The mean serum levels of MDA were higher in cases than controls (3.7 ± 1.6 nmol/ml vs. 2.8 ± 1.5 nmol/ml; P = 0.01). The GSH levels were lower in the cases than controls (31.5 ± 8.9 mg/dl vs. 36.6 ± 16.9 mg/dl; P = 0.064). Similarly, the mean FRAP levels were lower in the cases than controls (400 ± 70 nmol/ml vs. 430 ± 80 nmol/ml; P = 0.038). CONCLUSIONS: Patients with premature canities had a higher level of pro-oxidants and lower levels of antioxidants than controls. This is the first humble attempt to document the oxidative stress parameters in sera of patients with premature canities, further studies with larger sample size are required to reach a definite conclusion.

Effect of Carbamazepine and Valproate Monotherapy on Cardiovascular Risks in Epileptic Children.

OBJECTIVE: We determined the effects of carbamazepine and valproic acid on the serum lipids and apolipoprotein A and B in epileptic children on long-term monotherapy and 3 months after drug discontinuation. METHOD: Thirty-three epileptic children (17 boys, 16 girls, mean age 9.79 ± 2.5 years) were evaluated for serum lipids and lipoprotein results at the initiation of antiepileptic drug tapering and 3 months after cessation of antiepileptic therapy. RESULTS: In the carbamazepine group (n = 13), there was no significant difference in the lipid profile at the end of therapy or at 3 months after the discontinuation, whereas in the valproate group (n = 20), triglycerides and apoprotein B and high-density lipoprotein cholesterol increased significantly 3 months after discontinuation. The ratios of total cholesterol:high-density lipoprotein improved but low-density lipoprotein:high-density lipoprotein and apolipoprotein:apolipoprotein remained unchanged. CONCLUSION: Because these ratios are better predictor of atherosclerosis risk than the absolute values, the overall risk is not increased by the long-term use of carbamazepine and valproate.

Study of variables affecting critical value notification in a laboratory catering to tertiary care hospital.

During post-analytical phase, critical value notification to responsible caregiver in a timely manner has potential to improve patient safety which requires cooperative efforts between laboratory personnel and caregivers. It is widely accepted by hospital accreditors that ineffective notification can lead to diagnostic errors that potentially harm patients and are preventable. The objective of the study was to assess the variables affecting critical value notification, their role in affecting it's quality and approaches to improve it. In the present study 1,187 critical values were analysed in the Clinical Chemistry Laboratory catering to tertiary care hospital for neuropsychiatric diseases. During 25 months of study period, we evaluated critical value notification with respect to clinical care area, caregiver to whom it was notified and timeliness of notification. During the study period (25 months), the laboratory obtained 1,279 critical values in clinical chemistry. The analytes most commonly notified were sodium and potassium (20.97 & 20.8 % of total critical results). Analysis of critical value notification versus area of care showed that critical value notification was high in ICU and emergency area followed by inpatients and 64.61 % critical values were notified between 30 and 120 min after receiving the samples. It was found that failure to notify the responsible caregiver in timely manner represent an important patient safety issue and may lead to diagnostic errors. The major area of concern are notification of critical value for outpatient samples, incompleteness of test requisition forms regarding illegible writing, lack of information of treating physician and location of test ordering and difficulty in contacting the responsible caregiver.

Intergenotypic variation of Vitamin B12 and Folate in AD: In north indian population.

OBJECTIVES: Changes in lifestyle habits such as diet modification or supplementation have been indicated as probable protective factors for a number of chronic conditions including Alzheimer's disease (AD). With this background, we aim to hypothesize that whether C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene contributes towards the risk of developing AD and its association with vitamin B12 and folate levels. MATERIALS AND METHODS: A case-control study comprising of total 200 subjects, within the age group of 50-85 years. Their blood samples were analyzed for serum folate, vitamin B12 levels, and MTHFR C677T polymorphism by restriction fragment length polymorphism (RFLP). RESULTS: The mean plasma levels of vitamin B12 and folate were significantly lower in study group when compared to the control group (P < 0.001). Genotypic and allelic frequency of MTHFR gene in both groups was found to be significant (P < 0.05). The intergenotypic variations of vitamin B12 and folate were found to be significant (P < 0.001). CONCLUSION: We concluded that the subjects with homozygous mutated alleles are more prone to AD and also pointed out the influence of presence/absence of MTHFR T allelic variants on serum folate and vitamin B12 levels.

Gene-gene and gene-environment interaction on the risk of Parkinson's disease.

BACKGROUND: Even with numerous studies the cause of Parkinson's disease (PD) remains elusive. It has been hypothesized that interactions between genetic and environmental factors may play an important role in the pathogenesis of PD. OBJECTIVES: To examine the gene-gene and gene-environment interaction on PD risk with respect to gene polymorphism of cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1), organochlorine pesticides (OCPs) and metals. METHODS: This study included 70 patients of PD and 100 age-matched controls. The restriction fragment length polymorphism was used for analysis of genetic polymorphism. OCPs and serum metal levels were estimated by using gas chromatography and an autoanalyser respectively. RESULTS: The CYP2D6*4 mt and GSTP1 *B allelic variants were significantly associated with increase in PD risk. We found a statistically significant difference in ß -hexachlorocyclohexane (ß-HCH), dieldrin, 1,1-dichloro-2,2-bis(pchlorophenyl) ethylene (pp'-DDE) and copper levels between the patients and controls. We found significantly high levels of ß-HCH, dieldrin and pp'-DDE in the CYP2D6*4 mt allelic variants, ß-HCH and pp'-DDE in the GSTP1*B allelic variants and dieldrin in the GSTP1*C allelic variants when comparing CYP2D6*4 non-mt, GSTP1 non-*B and GSTP1 non-*C allelic variants in patients of PD respectively. CONCLUSION: This study demonstrates that the CYP2D6*4 and GSTP1 genes may be considered as candidate genes for PD and they may also interact with ß- HCH, dieldrin and pp'-DDE to influence the risk for PD.

Polymorphism in Cytochrome P450 2D6, Glutathione S-Transferases Pi 1 Genes, and Organochlorine Pesticides in Alzheimer Disease: A Case-Control Study in North Indian Population.

OBJECTIVES: It has been assumed that the association between Alzheimer disease (AD) and pesticides may be stronger among genetically susceptible individuals. The aim of the study was to examine the genetic polymorphism in cytochrome P450 2D6 (CYP2D6) and glutathione S-transferases pi 1 (GSTP1) with respect to organochlorine pesticides (OCPs) and metals in AD. METHODS: This study included 100 patients with AD and 100 age-matched controls. The genetic polymorphisms were analyzed by restriction fragment length polymorphism. The OCPs and serum metal levels were determined using gas chromatography and an autoanalyzer, respectively. RESULTS: We found a statistically significant association between AD and high levels of ß-hexachlorocyclohexane (ß-HCH; odds ratio [OR] = 2.064, 95% confidence intervals [95% CIs] = 1.373-3.102, dieldrin [OR = 2.086, 95% CI = 1.224-3.555], and copper [OR = 1.038, 95% CI = 1.012-1.064). The significant low level of magnesium (OR = 0.151, 95% CI = 0.047-0.489) even appears to have a protective role against AD. The GSTP1*B (P = .009) and GSTP1*C (P = .011) allelic variants were associated with increase in AD risk. CONCLUSION: This study demonstrates that the GSTP1*B and *C allelic variants may be considered a candidate gene for AD. It can be suggested that although CYP2D6*4 polymorphism is not a risk of AD, the CYP2D6*4 and GSTP1 polymorphism may interact with ß-HCH, dieldrin, and copper to influence the risk of AD.

APOE and LRPAP1 gene polymorphism and risk of Parkinson's disease.

Epidemiologic findings suggest that lipids and alteration in lipid metabolizing protein/gene may contribute to the development of neurodegenerative disorders. The aim of the current study was to determine the serum lipid levels and genetic variation in two lipid metabolizing genes, low-density lipoprotein receptor-related protein-associated protein (LRPAP1) and apolipoprotein E (APOE) gene in Parkinson's disease (PD). Based on well-defined inclusion and exclusion criteria, this study included 70 patients with PD and 100 age-matched controls. LRPAP1 and APOE gene polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism, respectively. Fasting serum lipid levels were determined using an autoanalyser. The logistic regression analysis showed that high levels of serum cholesterol [odds ratio (OR) = 1.101, 95 % confidence interval (CI95%) = 1.067-1.135], LRPAP1 I allelic variant alone (OR = 2.766, CI95% = 1.137-6.752) and in combination with APOE ε4 allelic variant (OR = 4.187, CI95% = 1.621-10.82) were significantly associated with increase in PD risk. Apart from that, the high levels of LDL cholesterol appears to have a protective role (OR = 0.931, CI95% = 0.897-0.966) against PD. The LRPAP1 I allelic variant may be considered a candidate gene for PD, predominantly in patients having the APOE ε4 allelic variant.

A cross-sectional study on thyroid status in North Indian elderly outpatients with dementia.

BACKGROUND: Several population based studies have demonstrated an association between hypo-or hyperthyroidism and dementia in last two decades. As a consequence, thyroid stimulating hormone has become part of the screening laboratory test for dementia. AIM: The aim of the present study was to evaluate the association between thyroid function and Alzheimer's disease (AD) and vascular dementia (VaD) and to determine the risk of AD and VaD in clinically euthyroid patients. MATERIALS AND METHODS: A cross-sectional hospital based study was carried out in subjects diagnosed with AD/VaD and were assessed for thyroid status as routine screening test. RESULTS: Free T3, free T4 and TSH were studied in 114 AD patients (mean age: 65 years), 35 VaD patients (mean age: 62 years) and 105 control subjects (mean age: 62 years). In AD group, TSH levels were significantly lower than controls (P = 0.00) and for each unit increase in TSH level, the odds of having dementia decreased by 37.1%. No such relation was seen in VaD. CONCLUSION: The results suggest a consistent association of subclinical hyperthyroidism and AD.

Organochlorine pesticide levels and risk of Parkinson's disease in north Indian population.

The cause of Parkinson's disease (PD) remains elusive, but environmental chemical exposures have been postulated to be involved in the etiology of PD. We examined the association between the persistent organochlorine pesticides (OCPs) and PD in the North Indian population. This case control study included 70 PD and 75 control subjects in the age group of 50 to 85 years. Blood samples were collected and high-purity grade hexane and acetone (2 : 1 ratio) were used for extraction of organochlorine residues. OCPs (hexachlorocyclohexane (HCH), aldrin, dieldrin, endosulfan, pp'-Dichlorodiphenyldichloroethylene (pp'-DDE), op'-DDE, pp'- Dichlorodiphenyltrichloroethane (pp'-DDT), op'-DDT, pp'-dichlorodiphenyldichloroethane (pp'-DDD) and op'-DDD) were quantitatively estimated by using gas chromatography. The most frequently detected OCP was dieldrin, which was present in 9.3% of control and 61.4% of PD. The strongest predictor was ß-hexachlorocyclohexane (ß-HCH), which reported an odds ratio of 2.566, indicating that for every additional one unit of ß-HCH, patients had 2.566 times more chances of presence of PD. This study indicates that increased level of ß-HCH and dieldrin may be associated with the risk of PD.

Gene-environment interaction in Alzheimer's disease.

OBJECTIVES: The aim was to examine the gene environment (GxE) interaction with reference to APO E genotypes, serum lipids and organochlorine pesticides (OCPs) as one of the factors in the etiology of Alzheimer's disease (AD). METHODS: A case control study was used to examine, APOE HhaI polymorphism by polymerase chain reaction (PCR)/PCRrestriction fragment length polymorphism method, serum lipids by autoanalyser and OCPs by gas chromatography (GC). RESULTS: APOE ∈4 allele frequency was significantly high (p=0.000, OR=5.73, CI=2.68-12.50) in AD as compared to controls. The serum cholesterol, ß- hexachlorocyclohexane and dieldrin are risk factors for AD independent of the APOE ∈4 risk allele, recording an odds ratio of 1.16, 11.38 and 10.45 respectively. CONCLUSION: GxE interactions exist with APOE ∈4 allele status that need to be considered for the study design and analysis of such data in future studies of AD.

Role of intervention on laboratory performance: evaluation of quality indicators in a tertiary care hospital.

Quality in laboratory has huge impact on diagnosis and patient management as 80-90% of all diagnosis is made on the basis of laboratory tests. Monitoring of quality indicators covering the critical areas of pre-analytical, analytical and post-analytical phases like sample misidentification, sample rejection, random and systemic errors, critical value reporting and TATs have a significant impact on performance of laboratory. This study was conducted in diagnostic laboratories receiving approximately 42,562 samples for clinical chemistry, hematology and serology. The list of quality indicators was developed for the steps of total testing process for which errors are frequent and improvements are possible. The trend was observed for all the QI before and after sensitisation of the staff over the period of 12 months. Incomplete test requisition form received in the lab was the most poor quality indicator observed (7.89%), followed by sample rejection rate (4.91%). Most significant improvement was found in pre- and post-analytical phase after sensitisation of staff but did not have much impact on analytical phase. Use of quality indicators to assess and monitor the quality system of the clinical laboratory services is extremely valuable tool in keeping the total testing process under control in a systematic and transparent way.

Effect of pre-analytical errors on quality of laboratory medicine at a neuropsychiatry institute in north India.

Advances in instrument technology and automation have simplified tasks in laboratory diagnostics reducing errors during analysis thereby improving the quality of test results. However studies show that most laboratory errors occur in the pre-analytical phase. In view of the paucity of studies examining pre-analytical errors, we examined a total of 1513 request forms received at our laboratory during a 3 month period. The forms were scrutinized for the presence of specific parameters to assess the pre-analytical errors affecting the laboratory results. No diagnosis was provided on 61.20% of forms. Type of specimen was not mentioned in 61.60% of the forms and 89.25% of all forms were illegible. Critical results were encountered in 17.30% of patients, and of these 76.60% were not communicated due to incomplete forms. Thus, by following standard operating procedures vigorously from patient preparation to sample processing the laboratory results can be significantly improved without any extra cost.

Role of vitamin B(12), folate, and thyroid stimulating hormone in dementia: A hospital-based study in north Indian population.

BACKGROUND: Vitamin B(12) and folate represent modifiable risk factors for dementia. They may increase the risk of Alzheimer's dementia (AD) and vascular dementia (VaD) as their deficiency can increase the homocysteine level due to slowed methylation reaction. Homocysteine has a neurotoxic effect that could lead to neurologic disturbances. Hence, it is important to explore the status of serum B(12) and folate in AD and VaD to evolve the treatment strategies for the same. OBJECTIVES: A retrospective study was conducted to assess the levels of vitamin B(12), folate, and thyroid stimulating hormone (TSH) in serum and the relationship of these factors, including age and sex to cognitive decline in VaD, AD, and dementia due to other causes (DOC). MATERIALS AND METHODS: Serum vitamin B(12), folate, TSH, and total cholesterol were studied in 32 AD patients (mean age: 65 years), 12 VaD patients (mean age: 61 years), 83 DOC (mean age: 65 years), and 127 control subjects (mean age: 49 years). RESULTS: In AD, VaD, and DOC, the levels of vitamin B(12) and folate were significantly lower (P < 0.002; 0.026; 0.002 for vitamin B(12) and P < 0.000 in all the 3 groups for folate) as compared with the controls. Similarly, TSH levels were significantly lower in AD and DOC (P < 0.008; 0.038) as compared with the controls. CONCLUSION: Vitamin B(12) and folate were significantly low in both AD and VaD patients. Hence, B vitamin supplementation should be considered as possible targets for the therapeutic intervention in dementia.

Hyperammonemia and hepatic status during valproate therapy.

The present study was conducted to assess correlation of ammonia levels with valproate levels in epileptic patients presenting with valproate toxicity and also whether liver enzymes and ammonia levels could serve as biochemical marker of valproate toxicity. 100 patients with epilepsy who had received valproate therapy for more than 12 months and had presented with valproate toxicity and 100 controls were included in the study. The serum valproate, ammonia and liver enzymes were measured in these subjects. In patients with valproate toxicity, the mean level of serum valproate was 110.91 ± 28.68 mg/dL (therapeutic range 50-100 mg/dL). Serum ammonia was higher (86.37 ± 39.90 µg/dL) in patients with valproate toxicity compared to controls (68.73 ± 30.07 µg/dL). Out of 100 patients, only 37 patients had serum valproate level > 120 mg/dL and 22 patients had raised levels of valproate as well as ammonia. Age < 30 years and serum ammonia > 69 µg/dL is risk factors for valproate toxicity. Serum ammonia, liver enzymes should be regularly investigated in patients on valproate therapy for early diagnosis of valproate toxicity.