Glutamatergic and GABAergic TCA cycle and neurotransmitter cycling fluxes in different regions of mouse brain

The ¹³C nuclear magnetic resonance (NMR) studies together with the infusion of ¹³C-labeled substrates in rats and humans have provided important insight into brain energy metabolism. In the present study, we have extended a three-compartment metabolic model in mouse to investigate glutamatergic and GABAergic tricarboxylic acid (TCA) cycle and neurotransmitter cycle fluxes across different regions of the brain. The ¹³C turnover of amino acids from [1,6-¹³C₂]glucose was monitored ex vivo using ¹H-[¹³C]-NMR spectroscopy. The astroglial glutamate pool size, one of the important parameters of the model, was estimated by a short infusion of [2-¹³C]acetate. The ratio V_cyc/V_TCA was calculated from the steady-state acetate experiment. The ¹³C turnover curves of [4-¹³C]/[3-¹³C]glutamate, [4-¹³C]glutamine, [2-¹³C]/[3-¹³C]GABA, and [3-¹³C]aspartate from [1,6-¹³C₂]glucose were analyzed using a three-compartment metabolic model to estimate the rates of the TCA cycle and neurotransmitter cycle associated with glutamatergic and GABAergic neurons. The glutamatergic TCA cycle rate was found to be highest in the cerebral cortex (0.91±0.05 μmol/g per minute) and least in the hippocampal region (0.64±0.07 μmol/g per minute) of the mouse brain. In contrast, the GABAergic TCA cycle flux was found to be highest in the thalamus–hypothalamus (0.28±0.01 μmol/g per minute) and least in the cerebral cortex (0.24±0.02 μmol/g per minute). These findings indicate that the energetics of excitatory and inhibitory function is distinct across the mouse brain.     

Poorer Survival Outcomes for Male Breast Cancer Compared with Female Breast Cancer May Be Attributable to In-Stage Migration

Background  

Male breast cancer accounts for less than 1% of all breast cancers, yet males have a worse prognosis than females with breast cancer.     

Polycyclic Aromatic Hydrocarbons and Digestive Tract Cancers: A Perspective

Cancers of the colon are most common in the Western world. In majority of these cases, there is no familial history and sporadic gene damage seems to play an important role in the development of tumors in the colon. Studies have shown that environmental factors, especially diet, play an important role in susceptibility to gastrointestinal (GI) tract cancers. Consequently, environmental chemicals that contaminate food or diet during preparation become important in the development of GI cancers. Polycyclic aromatic hydrocarbons (PAHs) are one such family of ubiquitous environmental toxicants. These pollutants enter the human body through consumption of contaminated food, drinking water, inhalation of cigarette smoke, automobile exhausts, and contaminated air from occupational settings. Among these pathways, dietary intake of PAHs constitutes a major source of exposure in humans. Although many reviews and books on PAHs and their ability to cause toxicity and breast or lung cancer have been published, aspects on contribution of diet, smoking and other factors toward development of digestive tract cancers, and strategies to assess risk from exposure to PAHs have received much less attention. This review, therefore, focuses on dietary intake of PAHs in humans, animal models, and cell cultures used for GI cancer studies along with epidemiological findings. Bioavailability and biotransformation processes, which influence the disposition of PAHs in body and the underlying causative mechanisms of GI cancers, are also discussed. The existing data gaps and scope for future studies is also emphasized. This information is expected to stimulate research on mechanisms of sporadic GI cancers caused by exposure to environmental carcinogens.     

Evidence of bluetongue virus serotype 21 (BTV-21) divergence

Bluetongue virus serotype 21 (BTV-21) was originally isolated from Australia, but has now been reported from India, Indonesia, China and Japan. We report the isolation, and sequencing of BTV-21 from India. The complete ORF sequence of VP2 gene of this isolate showed that it is closely related to recent BTV-21 isolates from Japan (93–94% identity), and distantly related to BTV-21 reference strain (86% identity). Our results, along with the available sequences of Japanese isolates, suggest that the currently circulating BTV-21 strains from India and Japan are divergent from the original strain(s) from Australia and shed light on designing molecular diagnostics for the detection of BTV.     

Analysis of Proteinuria Estimation Methods in Hypertensive Disorders of Pregnancy

Purpose of the Study

The gold-standard 24-h urine collection method for protein estimation is inconvenient and is associated with a delay in laboratory analysis. This study was undertaken to compare sulphosalicylic acid test, urine dipstick test, urine protein-to-creatinine ratio with 24-h urine protein estimation in pre-eclampsia cases.

Methods

This is a comparative study and consists of a single group of 764 subjects. This study was conducted in the Department of Obstetrics and Gynaecology in collaboration with the Department of Biochemistry, JIPMER, Pondicherry, India, from February 2011 to January 2014. The subjects included were 764 pre-eclampsia women. A first voided morning sample was obtained for sulphosalicylic acid test, dipstick test, urine protein and creatinine estimation and urine culture, and subsequent urine samples were collected for the 24-h urine protein estimation.

Main Findings

For significant proteinuria, sulphosalicylic acid test with 1 + proteinuria has sensitivity, specificity, PPV and NPV of 59, 48, 39, 67, whereas with 2 + has sensitivity, specificity,PPV and NPV of 44, 88, 75 and 67%, respectively, dipstick test with 1 + proteinuria has sensitivity, specificity, PPV and NPV of 71, 52, 54 and 70%, whereas with 2 + has sensitivity, specificity,PPV and NPV of 49, 87, 75 and 69%, respectively. The spot urine protein-to-creatinine ratio and 24-h urine protein were significantly correlated (r = 0.98; p < 0.0001). The cut-off value for the protein-to-creatinine ratio as an indicator of protein excretion ≥ 300 mg/day was 0.285. The sensitivity, specificity PPV and NPV were 100, 99, 100 and 99%, respectively.

Conclusion

The spot urine protein-to-creatinine ratio is a better method for estimation of proteinuria in pre-eclampsia.