Citric acid and polyols production by Aspergillus niger at high glucose concentration in solid state fermentation on inert support

Summary Aspergillus niger cultures at high initial glucose concentration (up to 400 g/1) on Amberlite as inert support were carried out. Citric acid was accumulated in the support showing high concentration (94.54 g/l) and productivity (1.35 g/l h) without inhibition related to the presence of metals (Mn²⁺, Zn²⁺, Co²⁺, Cu²⁺, and Ca²⁺) at high concentrations. Citric acid accumulation was clearly associated with both, glycerol production and to the age of the culture. Glycerol and erythritol, the major osmoregulator metabolites, were also produced (8.16 and 24.57 g/l respectively) at 400 g/l of glucose.     

Polymorphisms at 13 expressed human sequences containing CAG/CTG repeats and analysis in autosomal dominant cerebellar ataxia (ADCA) patients

Genetic anticipation – increasing severity and a decrease in the age of onset with successive generations of a pedigree – is clearly present in autosomal dominant cerebellar ataxia (ADCA). Anticipation is correlated with expansion of the CAG/CTG repeat sequence to sizes above those in the normal range through the generations of a pedigree. Genetic heterogeneity has been demonstrated for ADCA, with four cloned genes (SCA1, SCA2, SCA3/MJD, and SCA6) and three mapped loci (SCA4, SCA5 and SCA7). Another related dominant ataxia, dentatorubral-pallidoluysian atrophy (DRPLA), presents anticipation with CAG/CTG repeat expansions. We had previously analysed ADCA patients who had not shown repeat expansions in cloned genes for CAG/CTG repeat expansions by the repeat expansion detection method (RED) and had detected expansions of between 48 and 88 units in 17 unrelated familial cases. We present here an analysis of 13 genes and expressed sequence tags (ESTs) containing 10 or more CAG/ CTG repeat sequences selected from public databases in the 17 unrelated ADCA patients. Of the 13 selected genes and ESTs, 9 were found to be polymorphic with heterozygosities ranging between 0.09 and 0.80 and 2 to 17 alleles. In ADCA patients none of the loci showed expansions above the normal range of the CAG/CTG repeat sequences, excluding them as the mutation causing ADCA. Received: 28 May 1997 / Accepted: 30 June 1997     

Saroglitazar is noninferior to fenofibrate in reducing triglyceride levels in hypertriglyceridemic patients in a randomized clinical trial

Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500–1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = ?55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = ?41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated.     

TOS-sing aside the glycolytic role of HK2/hexokinase-II to activate autophagy

Hexokinase is the first enzyme in the glycolytic pathway catalyzing the reaction in which glucose is phosphorylated into glucose-6-phosphate. Mammals possess 4 isoforms of hexokinase; HK2 (hexokinase 2) is the predominant form in insulin-sensitive tissues such as adipocytes, as well as skeletal and cardiac muscle. In addition to its function in glucose metabolism, HK2 is associated with cardiomyocyte protection against mitochondrial-mediated apoptotic cell death; whether or not HK2 played a role in cardioprotective autophagy was yet to be discovered. However, in a recent study highlighted by a punctum in this issue of Autophagy, Roberts et al. addressed this possibility, uncovering a direct link between HK2, TORC1, and autophagy regulation.     

Probiotic Lactobacillus fermentum UCO-979C biofilm formation on AGS and Caco-2 cells and Helicobacter pylori inhibition

The ability of the human isolate Lactobacillus fermentum UCO-979C to form biofilm and synthesize exopolysaccharide on abiotic and biotic models is described. These properties were compared with the well-known Lactobacillus casei Shirota to better understand their anti-Helicobacter pylori probiotic activities. The two strains of lactobacilli synthesized exopolysaccharide as detected by the Dubois method and formed biofilm on abiotic and biotic surfaces visualized by crystal violet staining and scanning electron microscopy. Concomitantly, these strains inhibited H. pylori urease activity by up to 80.4% (strain UCO-979C) and 66.8% (strain Shirota) in gastric adenocarcinoma (AGS) cells, but the two species showed equal levels of inhibition (~84%) in colorectal adenocarcinoma (Caco-2) cells. The results suggest that L. fermentum UCO-979C has probiotic potential against H. pylori infections. However, further analyses are needed to explain the increased activity observed against the pathogen in AGS cells as compared to L. casei Shirota.