Sandhya Mishra

Evaluation of antioxidant deficit in schizophrenia.

Aim: Oxidative stress is a state in which there is disequilibrium between pro-oxidant processes and the antioxidant defense system in favor of the former and occurs as a consequence of increased production of free radicals or when the antioxidant defense system is inefficient or a combination of both events. A disturbance in the antioxidant defense system, including antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSHPx), due to free radical-induced oxidative injury has also been implicated in various neuropsychiatric disorders. Hence the role of these antioxidant enzymes and the changes in their level in blood and correlation with oxidative stress and the overall mechanism of defense were studied in a common psychiatric illness, schizophrenia. Materials and Methods: Fifty subjects of either sex ranging in age from 18 to 60 years, divided into two age groups (< 40 years and >40 years), diagnosed for schizophrenia; and 50 age- and sex-matched normal subjects as controls were included in the study. Blood samples were collected for the determination of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and reduced glutathione (GSH). Results: Significantly lower levels of the two antioxidant enzymes were found in schizophrenics compared to normal controls, with an increased oxidative stress as indicated by high blood MDA levels. The condition worsened with advancing age, smoking, among literate masses, and in chronic schizophrenics; whereas gender did not show any effect. Conclusion: It can be concluded that an imbalance in the antioxidant defense system, along with enzymatic antioxidants, occurs in schizophrenia due to the persistent oxidative stress. Modern life style perhaps also contributes to the condition.

Oxidative stress, α-tocopherol, ascorbic acid and reduced glutathione status in schizophrenics

A disturbance in the antioxidant defense system including α-tocopherol, ascorbic acid and reduced glutahtione metabolism due to free radical induced oxidative injury has been implicated in various neuro-psychiatric disorders. The roles of these antioxidants, changes in their blood levels and correlation with oxidative stress were studied in a common psychiatric illness Schizophrenia. Fifty-eight subjects of either sex ranging in age from 18–60 years divided into two age groups (≤40 and >40 years) diagnosed for schizophrenia, and forty age and sex-matched normal subjects as controls were included in the study. Blood samples were analyzed for malondialdehyde (MDA), α-tocopherol, total ascorbic acid (TAA), dehydro ascorbic acid (DHAA), reduced ascorbic acid (RAA), leucocyte ascorbic acid (LAA) and reduced glutathione (GSH). A decrease in the levels of α-tocopherol, total ascorbic acid and reduced glutathione was found in schizophrenics compared to normal controls. Further a significant rise in oxidative stress and decreased antioxidant status was observed in the chronic stage of schizophrenia as compared to those in acute condition. A significant rise in dehydroascorbic acid with concomitant fall in reduced ascorbic acid suggests scavenging action of ascorbic acid and its utilization with increased oxidative stress as indicated by high blood malondialdehyde levels. Leucocyte ascorbic acid, a better index of ascorbic acid status was also found to be reduced in schizophrenics, suggesting depletion of body stores of ascorbic acid and the condition worsened with advancing age.

Oxidative stress in metabolic syndrome.

As antioxidants play a protective role in the pathophysiology of diabetes and cardiovascular diseases, understanding the physiological status of antioxidant concentration among people at high risk for developing these conditions, such as Metabolic Syndrome, is of interest. In present study out of 187 first degree non-diabetic relatives and 192 non-diabetic spouses, 33.1% and 19.7% were found to have metabolic syndrome respectively. Subjects with metabolic syndrome (≥3 risk factors) had poor antioxidants status as reflected by significantly low levels of vitamin A, C & E and significantly increased (p<0.01) oxidative stress as compared to those without metabolic syndrome. At the same time serum insulin levels and insulin resistance were found to be significantly high (p<0.001) in metabolic syndrome. A strong positive correlation (r=0.946; p<0.001) between oxidative stress and insulin resistance was observed in metabolic syndrome. Low levels of antioxidants and increased oxidative stress with insulin resistance in metabolic syndrome suggests that besides therapeutic life style changes (TLC) as suggested in ATP III guidelines inclusion of antioxidant vitamins, fruits and vegetable could be beneficial to ward off the consequences of metabolic syndrome.

SERUM IRON, COPPER AND ZINC STATUS IN MATERNAL AND CORD BLOOD

Pregnancy is associated with increased demand of all the nutrients like Iron, Copper, Zinc etc. and deficiency of any of these could affect pregnancy, delivery and out come of pregnancy. With this consideration, the study was conducted on 80 mothers and newborns and 20 age matched control women. Out of 80 mothers, 34 had Iron deficiency anemia and their Hb levels were below 9.0 gm/d1. Pregnant women had significantly lower Iron and Zinc levels while Copper and Total Iron Binding Capacity (TIBC) were significantly higher (P<0.001). Newborns had significantly elevated Iron and Zinc levels and low levels of Copper and TIBC as compared to their mothers irrespective of Iron deficiency anemia. Micronutrient status of newborn was found to be dependent on their mothers micronutrient status. Besides, results also suggest micronutrient interactions, which are reflected in Iron/Zinc, Iron/Copper and Zinc/Copper ratios. In view of this, there is need for proper, adequate and balanced micronutrient supplementation during pregnancy to affect a healthy outcome.

Studies of biochemical parameters in breast cancer with and without metastasis.

The study includes 102 confirmed cases of carcinoma breast with and without metastasis and 25 healthy non-pregnant females. They were evaluated for blood levels of Ferritin, GSH, LDH, ALP, GGT and Hb before and 21 days after mastectomy. A significant increase (p<0.001) was observed in ferritin, LDH and GSH levels in cancer patients without metastasis in comparison to normal control subjects. Patients with metastasis had further elevated (p<0.001) levels of Ferritin, ALP and GGT as compared to non-metastatic patients. Mastectomy in both the cases i.e. with and without metastasis resulted in non-significant decrease in all the biochemical parameters suggesting that longer follow up could confirm post surgery decrease in the biochemical parameters. The results of the study suggest cost effective, usefulness of Ferritin, ALP, GGT and GSH/Hb ratio in differentiating breast cancer patients with and without metastasis which can be assayed in smaller laboratories.

Antioxidant status and peroxidative stress in mother and newborn -A pilot study.

Serum antioxidant status and peroxidative stress was estimated in 30 pregnant women, their newborn infants and 25 non-pregnant women. Serum Ascorbic acid, α-tocopherol, retinol & β-carotene levels were found to be significantly reduced and peroxidative stress was significantly higher in mothers as compared to matched non-pregnant women. Newborn had significantly higher levels of ascorbic acid as compared to their mother but had significantly lower levels of lipid soluble vitamins. The peroxidative stress in newborn was found to be significantly less as compared to their mothers. A positive correlation of ascorbic acid and α-tocopherol levels between mother and newborn reflects that their status in mother does influence the newborn status.

Impact of Chronic Lead Exposure on Selected Biological Markers

Lead poisoning remains a major problem in India due to the lack of awareness of its ill effects among the clinical community. Blood lead, δ-aminolevulinic acid dehydratase (δ-ALAD) and zinc protoporphyrin (ZPP) concentrations are widely used as biomarkers for lead toxicity The present study was designed to determine the impact of chronic lead exposure on selected biological markers. A total of 250 subjects, of both sexes, ranging in age from 20 to 70xa0years, were recruited. On the basis of BLLs, the subjects were categorized into four groups: Group A (BLL: 0–10xa0μg/dl), Group B (BLL: 10–20xa0μg/dl). Group C (BLL: 20–30xa0μg/dl) and Group D (BLL: 30–40xa0μg/dl) having BLLs of 3.60xa0±xa02.71xa0μg/dl, 15.21xa0±xa02.65xa0μg/dl, 26.82xa0±xa02.53xa0μg/dl and 36.38xa0±xa02.83xa0μg/dl, respectively. Significant changes in biological markers due to elevated BLLs were noted. The relation of BLL and biological markers to demographic characteristics such as sex, habits, diet and substances abuse (smoking effect) were also studied in the present investigation. Males, urban population, non-vegetarians, and smokers had higher blood lead levels. δ-ALAD activity was found to be significantly lower with increased BLL (Pxa0<xa00.001), while the ZPP level was significantly higher with increased BLL (Pxa0<xa00.001). Further, BLL showed a negative correlation with δ-ALAD (rxa0=xa0−0.425, Pxa0<xa00.001, Nxa0=xa0250) and a positive correlations with ZPP (rxa0=xa00.669, Pxa0<xa00.001, Nxa0=xa0250). Chronic lead exposure affects the prooxidant-antioxidant equilibrium leading to cellular oxidative stress.

Study of Trace Elements in Liver Cirrhosis Patients and Their Role in Prognosis of Disease

The objectives of this study are to evaluate trace elements in patients with liver cirrhosis and to assess their association with severity of the disease. One hundred fifty cirrhotic subjects of either sex ranging in age from 20–70xa0years were included in the study, and the results were compared with 50 age- and sex-matched healthy control subjects. All cirrhotic subjects were assessed for severity of disease as mild (Child A), moderate (Child B), and severe (Child C) as per Child-Pugh classification. Routine investigations were done and trace elements (Cu, Zn, Se, and Mg) were analyzed on atomic absorption spectrophotometer. Serum level of copper was found significantly increased in patients with liver cirrhosis as compared to control group. Whereas serum zinc, selenium, and magnesium levels were significantly decreased in cirrhotic subjects as compared to controls. Trace elements were compared with severity of liver cirrhosis. Serum copper concentration was slightly increased in patients with more severe clinical state of liver cirrhosis; however, mean level difference of copper among the Child-Pugh groups were statistically not significant. Moreover, there was no significant correlation between copper and Child-Pugh Score. However, copper showed a significant negative correlation with zinc. Serum zinc, magnesium, and selenium levels were significantly decreased with advancement of liver disease as compared to early stage of liver cirrhosis and showed a significant negative correlation with Child-Pugh Score. Trace element abnormalities may reflect the condition of liver dysfunction. These results suggest that liver dysfunction may alter the metabolism of trace elements. Our study shows that micronutrients status in liver cirrhosis correlates well with severity of liver cirrhosis. Micronutrients supplementation in liver cirrhotic patients may prevent progression of disease and development of complications; however, further research needs to be done.

The biochemical womb of schizophrenia: A review.

The conclusive identification of specific etiological factors or pathogenic processes in the illness of schizophrenia has remained elusive despite great technological progress. The convergence of state-of-art scientific studies in molecular genetics, molecular neuropathophysiology, in vivo brain imaging and psychopharmacology, however, indicates that we may be coming much closer to understanding the genesis of schizophrenia. In near future, the diagnosis and assessment of schizophrenia using biochemical markers may become a “dream come true” for the medical community as well as for the general population. An understanding of the biochemistry/ visa vis pathophysiology of schizophrenia is essential to the discovery of preventive measures and therapeutic intervention.

METABOLIC SYNDROME : EARLY IDENTIFICATION PREVENTS TYPE II DIABETES AND CARDIOVASCULAR DISEASE

The global prevalence of type 2 diabetes is expected to double in the period 2000 to 2025 and may reach a level of almost 300 million people i.e. 5-7.6% of the total global population by the year 2025. Patients with type 2 diabetes are at increased risk of coronary heart disease and stroke, which are the most common causes of cardiovascular disease. Atherosclerotic cardiovascular disease is the principle cause of death, disability and excess health care cost in diabetes. The patients with diabetes are more likely to die from first event of cardiovascular disease than their non-diabetic counter parts. Thus the efforts for early diagnosis and prevention of type 2 diabetes may prevent its costlier complications i.e. cardiovascular and renal diseases. The association of type 2 diabetes and cardiovascular disease has led to the hypothesis that both arise from common antecedent or common factors like Insulin resistance, Obesity, Dyslipidemia, Hypertension etc. It is rare to see type 2 diabetes, dyslipidemia, obesity or hypertension in isolation. Initially Gerald Reaven in 1988 described this as Syndrome X, and proposed that resistance to insulin mediated glucose disposal and consequent hyperinsulinemia is the pathological interface of several complex metabolic alterations and diseases (1). This concept was later codified by World Health Organization (WHO) as Metabolic Syndrome. In 1998 WHO proposed a definition of metabolic syndrome which states that a person has metabolic syndrome if he or she has diabetes, impaired glucose tolerance, impaired fasting glucose or insulin resistance, plus 2 or more of the following abnormalities: Blood Pressure > 160/90 mmHg, Triglycerides > 150 mg/dl (1.695 mmol/L) & or HDL Cholesterol 0.90 male, > 0.85 female & or BMI > 30 kg/m 2 , Urinary albumin excretion rate > 20 μg/min and or Albumin/Creatinine