Serum S100B levels in patients with depression.

BACKGROUND: The biochemical basis of depression has been related to blood-brain barrier (BBB) allowing/restricting a number of components to enter the brain milieu from the peripheral plasma milieu. S100B has been associated with BBB damage and is used as a marker of its integrity. Several studies have reported that depressive patients have increased levels of S100B in serum and cerebrospinal fluid. MATERIALS AND METHODS: Forty-two confirmed cases of depression, 13-25 years of ages were recruited from the Department of Psychiatry, All India Institute of Medical Sciences during the period from January 2013 to June 2014 along with 42 healthy controls of comparable age and sex. Psychometric evaluation of the patients and controls was done to assess the severity of depression using Beck's Depression Inventory-II and Hamilton Depression Rating Scale. Medical assessment and laboratory investigations were done. Serum S100B levels were measured using Sandwich ELISA. The results obtained were statistically analyzed. RESULTS: Levels of serum S100B were significantly elevated in patients with major depression as compared to controls. Significantly higher levels of S100B were seen only in females as compared to their healthy counterparts. Serum S100B was higher in depressed participants with the recurrent disorder than those with single episode. No correlation of levels of this marker was seen with clinical severity of the patients. It was found that with increased duration of illness for which the patient was being treated with antidepressants, the patients had higher levels of S100B. CONCLUSIONS: Serum S100B can be used as a biomarker of depression.

Alterations in mitochondrial membrane potential in peripheral blood mononuclear cells in Parkinson's Disease: Potential for a novel biomarker.

BACKGROUND: Progressive apoptosis in the dopaminergic neurons of substantia nigra lead to Parkinson's disease. Since neurons require substantially higher supply of energy, their mitochondria have a pivotal status in neuronal survival. These organelles have a key role to play in apoptosis and any impairment thereof may lead to apoptosis mediated cell death. OBJECTIVES: To evaluate and compare the mitochondrial membrane potential (Δψ) in Parkinson's disease patients and healthy controls. METHODS: We evaluated the mitochondrial membrane potential (Δψ) in the peripheral blood mononuclear cells by Flow cytometry using a lipophillic cationic dye JC-1 in Parkinson's disease patients (N = 61) and healthy controls (N = 37). RESULTS: JC-1 fluorescence was measured and represented as percentage positivity i.e., Mean±SEM in FL-2 (representing non-apoptotic aggregates) and FL-1 (indicating apoptotic cell population having depolarized or damaged mitochondria) channels. The ratio of % FL-2 and % FL-1, which is an indicator of cellular mitochondrial membrane potential, was found to be significantly higher in healthy controls (Mean±SEM = 60.48±18.42) as compared to patients (Mean±SEM = 24.30±4.671) in both stimulated and unstimulated conditions. CONCLUSIONS: Mitochondrial membrane potential is altered and hence its evaluation in peripheral blood mononuclear cells may serve as an early marker of apoptosis in PD and, therefore, may pave way for early interventions. Since Δψ has a role in the maintenance of electrochemical gradient, the disruption of which may lead to neuronal apoptosis, Δψ is intricately nested within etiopathogenesis of PD and may prove to be useful in design of diagnostics, prognostics and therapeutics for PD.

Toluidine blue: rapid and simple malaria parasite screening and species identification.

Malaria, a febrile illness mostly confined to the tropical countries is transmitted by bite of infected female Anopheles mosquito. In 2015 alone, 88% of the malaria burden and 90% deaths due to malaria were confined to the African and Asian countries. Although number of tests are available for rapid diagnosis and screening for malaria, peripheral blood smear examination remains the gold standard. Leishman stain is recommended by WHO however herein we evaluate one of the alternative methods of staining which is simple and rapid. Fifty patients attending the various outpatient departments of the tertiary care hospital with fever and suspected to have malaria were selected. Two thin-air dried smears prepared from the peripheral venous blood from these subjects were stained by Leishman and Toluidine blue method. The findings of the slides by two independent qualified professionals were noted and the results were analyzed. A total of 14% (7/50) cases were diagnosed to have malaria. All the malaria cases which were positive in Leishman stain were also detected in Toluidine blue stain. Malarial parasites were clearly visible against the homogenously light green background in Toluidine blue. The detection of malarial parasite by Toluidine blue was quick, easy and confirmative. Toluidine blue stained peripheral blood smear allows for easy identification and speciation of malarial parasite at low magnification and in shorter period of time.

Cross-sectional study of nutritional markers in pregnancy.

OBJECTIVES: To note the value of serum Vitamin B12, folic acid, and ferritin in normal and high-risk pregnancies (HRPs) in patients attending antenatal clinic at All India Institute of Medical Sciences (AIIMS). MATERIALS AND METHODS: This is a cross-sectional study where a total of 282 patients attending Gynaecology Outpatient Department at AIIMS, New Delhi, India were recruited. Among the 282 subjects, 251 were pregnant, and 31 were controls. The serum was tested for serum Vitamin B12, serum folic acid, and serum ferritin levels using Beckman Coulter Access 2 immunoassay. RESULTS: The median value of serum folic acid level in pregnant women was 12 pg/ml with range being 2-20 pg/ml in contrast to 8 pg/ml with range being 3-20 pg/ml in nonpregnant female. This difference was statistically significant. (P = 0.05). There was no significant difference in the median level of serum Vitamin B12 and serum ferritin in pregnant and nonpregnant group. Serum Vitamin B12 level was lower in the third trimester (127 pg/ml) than in first trimester (171 pg/ml) and the difference is statistically significant (P = 0.03). Serum ferritin levels were also significantly lower in the second trimester (16.4 pg/ml) than third trimester (24.55 pg/ml). Although the median serum folic acid level was lower in the first trimester (9.84 pg/ml) than in second trimester (10.8 pg/ml) and in the third trimester (13.18 pg/ml) but the difference was not statistically significant. There was no significant difference in Vitamin B12 level in HRPs (median value 134 pg/ml) as compared to low-risk pregnancies (149.5 pg/ml). CONCLUSION: Serum folic acid levels are significantly higher during pregnancy as compared to nonpregnant state. However, there was no significant difference in the median level of serum Vitamin B12 and serum ferritin in pregnant and nonpregnant group. Serum folic acid level and ferritin level were significantly higher in HRPs compared to low-risk pregnancies.

Cross-sectional study of serum parathyroid hormone level in high-risk pregnancies as compared to nonpregnant control.

OBJECTIVES: To note the value of serum parathyroid hormone (PTH) levels in normal and high-risk pregnancies (HRP) in patients attending antenatal visits at All India Institute of Medical Sciences (AIIMS). MATERIALS AND METHODS: This is a cross-sectional study where a total of 282 patients attending Gynecology Outpatient Department at AIIMS, New Delhi were recruited. Among the 282 subjects, 251 were pregnant, and 31 were controls. The serum was tested for serum PTH levels using Beckman coulter access 2 immunoassay. RESULTS: The median value of PTH level in pregnant women was 31.6 pg/ml with range being 0.8-505.5 pg/ml in contrast to 45.9 pg/ml with range being 19-102.7 pg/ml in nonpregnant female. This difference was statistically significant (P = 0.0012). There was no significant difference in median level of PTH in different age group. Although the median PTH levels were lower in second trimester (25.25 pg/ml) than in first trimester (35.5 pg/ml) and in third trimester (32.4 pg/ml), the difference was not statistically significant. There was no significant difference in PTH level in HRP (median value - 31.6 pg/ml) as compared to low-risk pregnancies (31.5 pg/ml). CONCLUSION: Serum PTH levels are significantly lower during pregnancy as compared to nonpregnant state. However, age, parity, and HRP did not alter PTH level during pregnancy.

Volume, conductivity, and scatter parameters as diagnostic aid to bacterial sepsis: A tertiary care experience.

UNLABELLED: INTRODUCTION AND MATERIALS AND METHODS: Early diagnosis of sepsis is extremely important to reduce high mortality and morbidity. In this study, clinical usefulness of the volume, conductivity and scatter parameters (mean channels of cell volume, conductivity, and light scatter) in neutrophils was analyzed for predicting acute bacterial infection, which are obtained by the Coulter LH 750 Hematology Analyzer (Beckman Coulter, Fullerton, CA, USA) during automated differential counts. RESULTS: Peripheral blood samples from 162 patients with positive blood cultures for bacteria and 40 healthy controls were studied. We observed a significant increase in the mean channel of neutrophil volume (MNV) from septic patients compared with control subjects (156 ± 13.5 vs. 143 ± 4.8; P < 001). DISCUSSION AND CONCLUSION: An elevation of the MNV was associated with a higher white blood cell count and percentage of neutrophils and was present even in patients who did not have leukocytosis or neutrophilia. With a cut-off of 149 for the MNV, a specificity of 91.4% and sensitivity of 88.7% were achieved. As a quantitative, objective, and more sensitive parameter, we propose that the MNV has a potential to be an additional indicator for acute bacterial infection.

Serum cytokines and anxiety in adolescent depression patients: Gender effect.

The present study compares the serum cytokine levels between adolescent depression patients and healthy controls and assesses correlation between depression, anxiety scores and serum levels of eight cytokines. Study also checked the variation in serum levels with medication status (medication free/naïve vs. patients on medication). Following clinical and psychometric assessment of 77 adolescent (aged 13-18 years) depression patients (49 males and 28 females; 56 medication free/naïve) and 54 healthy controls (25 males, 29 females), eight cytokines (IL-1ß, IL-2, IL-6, IL-10, TNF-α, IFN-γ, TGF-ß1 and IL-17A {denoted IL-17 throughout}) were measured in serum using ELISA. Depressed adolescents had significantly high levels of IL-2 (p<0.001) and IL-6 (p=0.03) as compared to controls. The female population skewed the result of one cytokine (IL-6) in patients. Anxiety scores showed positive correlation (only in female patients) with IL-1ß, IL-10 and negative correlation with TGF-ß1 and IL-17. The gender effect in relationship between anxiety and cytokines was not straightforward. On comparing study groups on the medication/naïve status, IL-2 and TGF-ß1 showed significant difference between the groups (p<0.001, p=0.007 higher in medicated). Depression in adolescents was associated with elevation of proinflammatory serum cytokines with a gender bias for females. Anxiety scores correlated negatively with TGF-ß1 and IL-17.

A cross-sectional study of tumor markers during normal and high-risk pregnancies.

OBJECTIVE: To determine tumor marker concentrations during normal and high-risk pregnancies. METHODS: The present cross-sectional study included women attending the gynecology outpatient department at All India Institute of Medical Sciences, New Delhi, India, between November 1, 2012 and March 31, 2013. Their serum was assayed for carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 15-3 (CA15-3). RESULTS: A total of 251 pregnant women and 31 nonpregnant women were included. Median CEA value was lower among pregnant women than among nonpregnant women (1.2µg/L vs 1.4µg/L; P=0.006), whereas that of CA15-3 was higher (16.7U/mL vs 12.3U/mL; P=0.03). CA19-9 concentration was higher among pregnant women aged 25-29years (7.0U/mL) or 30-34years (7.2U/mL) than among those aged 20-24years (4.2U/mL; P=0.01 for both). The CA15-3 level was increased during the second (13.0U/mL) and third (60.5U/mL) trimesters compared with the first trimester (9.5U/mL) (P≤0.01 for both comparisons). It was also raised in high-risk pregnancies (33.7U/mL), specifically pregnancies complicated by gestational diabetes mellitus (39.7U/mL), intrahepatic cholestasis of pregnancy (64.3U/mL), or heart disease (54.0U/mL) (P<0.05 for all). CONCLUSION: CA15-3 concentrations rise during pregnancy, but whether this increase can be attributed to physiological changes in breast tissue needs to be investigated further.

Synergistic epistasis of paraoxonase 1 (rs662 and rs85460) and apolipoprotein E4 genes in pathogenesis of Alzheimer's disease and vascular dementia.

Genetic polymorphism and epistasis play a role in etiopathogenesis of Alzheimer's disease (AD) and vascular dementia (VaD). In this case-control study, a total of 241 patients were included in the study to see the effect of paraoxonase 1 (PON1; rs662 and rs85460) and apolipoprotein E (ApoE) genes in altering the odds of having AD and VaD along with serum PON and lipid profile. The presence of at least 1 variant allele of rs662, but not rs85460, increased the risk of having AD by 1.8-fold (95% confidence interval [CI]: 0.97-3.40) and VaD by 3.09-fold (95% CI: 1.4-6.9). The interaction between PON1 genes (rs662 and rs85460) and ApoE genes showed synergistic epistasis in altering the odds of significantly having both AD and VaD. On the other hand, low serum level of high-density lipoprotein and low level of serum PON activity were found associated significantly (P ≤ .001 in both cases) only in patients with VaD as compared to healthy control.

Coagulopathy as prognostic marker in acute traumatic brain injury.

CONTEXT: Coagulopathy frequently occurs following traumatic brain injury (TBI) and usually occurs 6-72 hour post-trauma. The incidence and the probable risk factors for development of coagulopathy and poor outcome following TBI are largely unknown and vary considerably. AIMS: To assess the incidence and probable risk factors for development of coagulopathy and to identify the risk factors for poor outcome in terms of median survival time following TBI. MATERIALS AND METHODS: In this prospective study over two years, patients of isolated moderate and severe traumatic brain injury (GCS≤12) admitted to trauma center had coagulation profile (PT, APTT, thrombin time, fibrinogen and D-dimer), arterial lactate and ABG analysis done on day of admission and on day three. Coagulopathy was defined as prothrombin time (PT) or/and activated partial thromboplastin time (APTT) more than 1.5 times the normal control. Incidence of in-hospital mortality was assessed in all cases. STATISTICAL ANALYSIS: A stepwise logistic regression analysis was performed to identify risk factors for coagulopathy and mortality in these patients. RESULTS: A total of 208 patients were enrolled in the study. The mean age was 32 ± 12 years and mean GCS was 7.1 ± 2.8. Coagulopathy was present in 46% (n = 96) of patients. Risk factors for development of coagulopathy were found out to be severity of head injury (OR: 2.81), elevated D-dimer (OR: 3.43), low hemoglobin (OR: 3.13), and effaced cisterns in the CT scan (OR: 2.72). Presence of coagulopathy (OR: 2.97) and severity of head injury (OR: 5.70) strongly predicted poor outcome, and were associated with a decreased median survival time. CONCLUSIONS: There is a high incidence of coagulopathy following TBI. The presence of coagulopathy as well as of severity of TBI are strong predictors of in-hospital mortality in these patients.

Serum neurotrophic factors in adolescent depression: gender difference and correlation with clinical severity.

BACKGROUND: Brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3) and glial cell line derived neurotrophic factor (GDNF) play critical role in growth, differentiation, maintenance and synaptic plasticity in neuronal systems which is more relevant in adolescence. The present study was undertaken to verify the 'neurotrophin hypothesis' in adolescent depression by (i) comparing serum concentrations of neurotrophic factors in depression patients and healthy control, and (ii) analyzing correlations between clinical severity and serum neurotrophin levels. METHODS: Eighty four adolescent (aged 13-18 years) depressed patients (56 males; 60 medication free/naive) and 64 healthy controls (39 males) were recruited. Severity of depression was measured by Beck's depression inventory, and anxiety by state-trait anxiety inventory. Measurement of serum neurotrophins was done by ELISA. RESULTS: Adolescents with depression had significantly lower levels of BDNF: mean diff. (95% C.I.): 2093.9 (1074.0, 3113.9), NGF: 813.3 (343.1, 1283.6) and GDNF: 158.8 (77.2, 240.4) compared to controls. On gender based analysis female controls had significantly increased trait anxiety scores [-1.1 (-1.8, -0.1)], as compared to control males. In the patient group, female patients had far lower level of NGF: 919.6 (210.9, 1628.3) and NT-3: 1288.8 (145.4, 2432.3) compared to male. BDI-II score showed a statistically significant (p<0.01) negative correlation with all four neurotrophins in male patients while in female patients such negative correlation was observed only with NGF and GDNF (p<0.01). LIMITATIONS: The study is cross-sectional from a tertiary care hospital. CONCLUSION: The novelty of the study lies in its large number of exclusively adolescent depression patients showing significant reduction of BDNF, NGF and GDNF serum levels as compared to controls. A gender bias with much reduction in female has also been recorded.

MTHFR (677 and 1298) and IL-6-174 G/C genes in pathogenesis of Alzheimer's and vascular dementia and their epistatic interaction.

Genetic risk factors play an important role in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VaD). In this case-control study, we examined C677T and A1298C (rs1801133 and rs1801131) polymorphism in the methylenetetrahydrofolate reductase (MTHFR) genes and their correlation with plasma levels of homocysteine (Hcy) in AD and VaD cases and evaluated the gene-gene interaction (epistasis) with IL-6-174 G/C (rs1800795). CC genotype was associated with elevated levels of plasma homocysteine (p = 0.004) as compared with genotype AA of rs1801131. In AD, we observed a significant (p = 0.04) association with C alleles of rs1801131. Regression analysis revealed that the presence of both rs1801133 T and rs1800795 C alleles increased the odds of developing AD by 2.5 and VaD by 3.7-fold. While rs1800795 (CC or GC) genotypes alone increased the odds of developing VaD by 2.2-fold, the presence of CC genotype of rs1801131 nullified this effect. The findings support the hypothesis that multiple genes are involved to alter the odds of developing AD and VaD.

Prognostic significance of D-dimer, natural anticoagulants and routine coagulation parameters in acute pancreatitis.

AIM: This study was conducted to assess the predictive value of coagulation abnormalities in determining disease severity and prognosis of acute pancreatitis (AP). METHODS: Patients of AP and 25 healthy volunteers were included in this prospective observational study. The final outcomes were disease severity assessed by Computed Tomography Severity Index, Acute Physiological Assessment and Chronic Health Evaluation--II, presence of organ failure and mortality. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), fibrinogen, antithrombin-III (AT-III), protein-C, and protein-S levels were assessed on day 0, 3 and 7 of admission. RESULTS: Of the 38 patients included, 13 died. Mean PT and TT were similar between patients and controls on any given day. PTT showed elevation on day 3 and 7 (p = 0.001) compared to controls, although fibrinogen and D-dimer were significantly higher in patients on all days. Protein C and AT-III were significantly lower in patients and more so in non survivors ( (p = 0.001)) than controls. Multiple logistic regression analysis revealed D-dimer levels > or = 400 - 800 ng/ml and AT- III level of < 71% at admission were associated with high mortality (OR 11.2, AUROC 0.70 and OR 16.6, AUROC 0.82 respectively) as well as predicted organ failure. CONCLUSION: Serum D-dimer and antithrombin-III levels can be used to assess disease severity and predict outcome of patients with acute pancreatitis.

Hypofibrinogenemia in isolated traumatic brain injury in Indian patients.

Coagulation abnormalities are common in patients with head injuries. However, the effect of brain injury on fibrinogen levels has not been well studied prospectively to assess coagulation abnormalities in patients with moderate and severe head injuries and correlate these abnormalities with the neurologic outcome. Consecutive patients with moderate (Glasgow Comma Scale (GCS),9-12) and severe (GCS≤8) head injuries were the subjects of this pilot study, All patients had coagulation parameters, including plasma fibrinogen levels measured. Clinical and computed tomography (CT) scan findings and immediate clinical outcome were analyzed. Of the 100 patients enrolled, only seven (7%) patients had hypofibrinogenemia (fibrinogen ≤200 mg/dL). The head injury was moderate in two patients and severe in five patients. Fibrinogen levels showed a progressively increasing trend in four patients (three with severe head injuries and one with moderate head injury). CT scan revealed subdural hematoma in five patients; extradural hematoma in one; and subarachnoid hemorrhage in another patient. Of the seven patients, two patients died during hospital. Large-scale prospective studies are needed to assess the fibrinogen level in patients with head injury and its impact on outcome.

Erythrocyte enzyme abnormalities in leukemias.

Red cell enzymes were assayed in a total of 67 patient including 24 patients with AML (19 relapse, 5 remission), 16 patients with ALL (10 relapse, 6 remission), 22 patients with CML and 5 patients with blastic CML. Diagnosis of leukemia was based on clinical presentation, peripheral blood smear and bone marrow examination (as per FAB classification). PK activity was significantly high in case of CML and blastic CML (p<0.01). Red cell HK was high in all leukemia subtypes. There was no alteration in red cell G6PD. Notably there was no PK deficiency in AML or G6PD deficiency in ALL. Activities of G6PD and PK could be correlated in cases of CML, AML, (p<0.05) and ALL (p<0.01) i.e. when there was increased activity of G6PD, PK activity also tended to be higher. HK activity showed a positive correlation with PK and G6PD activity in cases of CML (p<0.05), however in acute leukemia there was no such correlation. Alteration of enzyme activities among red cells in leukemia occurred only during relapse. At the time of remission there has been no significant alteration in any of the enzyme activities. It would therefore, appear that enzyme alterations seen in leukemia patients is due to abnormal pluripotent stem cell that has given to a leukemia cell. The fact that enzyme alterations have primarily occurred at the time of relapse would further substantiate that abnormalities of red cell enzymes may be the result of a derivation some circulating red cells from the abnormal pluripotent stem cell. With the recovery of normal stem cells function during remission, enzyme abnormalities tend to become normal.