Effects of alpha-ketoglutarate on lipid peroxidation and antioxidant status during chronic ethanol administration in Wistar rats

The effects of alpha-ketoglutarate (alpha-KG) on ethanol-induced hepatotoxicity were studied in biochemical experiments in rats. The levels of serum transaminases and thiobarbituric acid reactive substances were significantly increased in ethanol-treated rats. These levels were significantly decreased in alpha-KG- and ethanol-treated rats. Further, non-enzymatic (vitamins C and E) and enzymatic (superoxide dismutase and catalase) antioxidants were significantly decreased in ethanol-treated rats, and were increased in alpha-KG- and ethanol-treated rats. The biochemical alterations during alpha-KG treatment could be due to (i) the participation of alpha-KG in the non-enzymatic oxidative decarboxylation in the hydrogen peroxide decomposition process and (ii) enhancing the proper metabolism of fats which could suppress oxygen radical generation and thus prevent the lipid peroxidative damages in rats.     

Chondrosarcoma of the greater cornu of the hyoid: a case report and literature review

We report an unusual case of a young woman with chondrosarcoma affecting the greater cornu of the hyoid bone. Only a handful of reports of primary chondrosarcoma involving the hyoid exist in the world literature. The case described presented as a swelling in the submandibular triangle, and as such posed a particular clinical and radiologic diagnostic challenge. Our subsequent surgical management of this rare entity comprised local excision followed by close observation, and is defined in the context of the existing literature. Two years after surgery, the patient remained free of tumor recurrence; she was subsequently lost to follow-up.     

Intron 4 VNTR of endothelial nitric oxide synthase (eNOS) gene and diabetic retinopathy in type 2 patients in southern India

A 27-bp variable number tandem repeat (VNTR) in intron 4 of endothelial nitric oxide synthase (eNOS) gene has been associated with the risk for developing diabetic retinopathy (DR) in various ethnic populations. Hundred and eighty seven patients with retinopathy (cases; DR+) and 188 patients without retinopathy (controls: DR-) from southern India who had type 2 diabetes mellitus (T2DM) for more than 10 years, were included in the study. We could neither find significant allelic association with clinical severity of DR nor with macular edema. Our results suggest lack of association of intron 4 VNTR of eNOS gene with DR in southern India.     

Novel Soluble Flt-1 Isoforms in Plasma and Cultured Placental Explants from Normotensive Pregnant and Preeclamptic Women

Pregnant women who develop preeclampsia exhibit higher circulating levels of the soluble VEGF receptor-1 (sFlt-1). Recent findings suggest that soluble Flt-1 may contribute to the pathogenesis of preeclampsia by binding and neutralizing vascular endothelial growth factors (VEGF) and placental growth factor (PlGF). Existing literature identifies sFlt-1 as a 100 kDa glycoprotein, a product of an mRNA splice variant. We hypothesized that sFlt-1 expression may be more complex with multiple variants of sFlt-1 as well as multiple sources during normal pregnancy and preeclampsia. Using a combination of affinity purification of sFlt-1 by heparin-agarose and epitope specific antibodies, we performed Western blot analysis with epitope specific antibodies for sFlt-1. Plasma of preeclamptic women exhibits significantly higher amounts of a novel 145 kDa variant of sFlt-1, along with the 100 kDa isoform. We identified sFlt-1 variants in the conditioned medium from placental explant cultures that are hypoxia responsive with varying sizes, including 185, 145,100 and 60 kDa forms, as well as antigenicity. The 145 kDa was similar in antigenicity to the 100 kDa found in plasma whereas the 185 and 60 kDa sFlt-1 demonstrated different epitopes. Deglycosylation studies also confirm that there are multiple sFlt-1 polypeptides. Co-immunoprecipitation with VEGF suggests that these different sFlt isoforms can bind VEGF and therefore, may be of functional importance. Finally, comparison of sFlt-1 in the conditioned medium obtained from cultured cytotrophoblasts, peripheral blood mononuclear cells (PBMCs) and human uterine microvascular cells (HUtMVECs) exhibit mainly the100 kDa sFlt-1. Collectively these data suggest the presence of multiple isoforms of sFlt-1 in the circulation of women with preeclampsia as well as in uncomplicated pregnancies and the possibility of multiple sources. Placental hypoxia may contribute to sFlt-1 over expression but other regulatory mechanisms cannot be ruled out.     

A pilot validation of multi‐echo based echo‐planar correlated spectroscopic imaging in human calf muscles

A current limitation of MR spectroscopic imaging of multiple skeletal muscles is prolonged scan duration. A significant reduction in the total scan duration using the echo‐planar correlated spectroscopic imaging (EP‐COSI) sequence was accomplished using two bipolar readout trains with different phase‐encoded echoes for one of two spatial dimensions within a single repetition time (TR). The second bipolar readout was used for spatially encoding the outer k‐space, whereas the first readout was used for the central k‐space only. The performance of this novel sequence, called multi‐echo based echo‐planar correlated spectroscopic imaging (ME‐EPCOSI), was demonstrated by localizing specific key features in calf muscles and bone marrow of 11 healthy volunteers and five subjects with type 2 diabetes (T2D). A 3 T MRI–MRS scanner equipped with a transmit–receive extremity coil was used. Localization of the ME‐EPCOSI sequence was in good agreement with the earlier single‐readout based EP‐COSI sequence and the required scan time was reduced by a factor of two. In agreement with an earlier report using single‐voxel based 2D MRS, significantly increased unsaturated pools of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) and decreased IMCL and EMCL unsaturation indices (UIs) were observed in the soleus and tibialis anterior muscle regions of subjects with T2D compared with healthy controls. In addition, significantly decreased choline content was observed in the soleus of T2D subjects compared with healthy controls. Multi‐voxel characterization of IMCL and EMCL ratios and UI in the calf muscle may be useful for the non‐invasive assessment of altered lipid metabolism in the pathophysiology of T2D. Copyright © 2014 John Wiley & Sons, Ltd.