On the mechanism of the glucose-induced ATP catabolism in ascites tumour cells and its reversal by pyruvate.

Addition of glucose to Ehrlich-Landschütz ascites tumour cells preincubated for 30-60 min in phosphate-buffered Krebs-Ringer salt solution ("starved cells") resulted within 1-2 min in an approx. 90% decline of their ATP content and a massive accumulation of fructose 1,6-bisphosphate. These alterations, which took place under both aerobic and anaerobic conditions, were followed by a gradual spontaneous recovery with restoration of normal ATP and fructose 1,6-bisphosphate values. The transient derangement of the energy metabolism after glucose addition to starved ascites tumour cells by preventable by simultaneous addition of pyruvate or 2-oxobutyrate, or by preincubating the cells in the presence of glucose. The protective effect of pyruvate was duplicated by addition of phenazine methosulphate or NAD+ to the incubation medium. The data seem to warrant the conclusion that the glucose-induced ATP depletion is determined by a blockade of glycolysis at the stage of glyceraldehyde phosphate dehydrogenase caused by the failure of the cells to oxidize the NADH produced in the same reaction. The continued unrestrained action of 6-phosphofructokinase results in accumulation of fructose 1,6-bisphosphate, which constitutes a trap for the high-energy phosphate bonds of ATP. The primary metabolic disturbance appears to consist of a transient inhibition of pyruvate kinase with the resultant inability of the cells to maintain an unimpaired supply of pyruvate, as required for the lactate dehydrogenase-mediated oxidation of NADH. The regulatory mechanism underlying this phenomenon is discussed

Methylation pattern of mouse mitochondrial DNA.

The pattern of methylation of mouse mitochondrial DNA (mtDNA) was studied using several techniques. By employing a sensitive analytical procedure it was possible to show that this DNA contains the modified base 5-methylcytosine (m5Cyt). This residue occurred exclusively at the dinucleotide sequence CpG at a frequency of 3 to 5%. The pattern of methylation was further investigated by determining the state of methylation of several MspI (HpaII) sites. Different sites were found to be methylated to a different extent, implying that methylation of mtDNA is nonrandom. Based on the known base composition and nucleotide sequence of mouse mtDNA, the dinucleotide sequence CpG was found to be underrepresented in this DNA. The features of mtDNA methylation (CpG methylation, partial methylation of specific sites and CpG underrepresentation) are also characteristic of vertebrate nuclear DNA. This resemblance may reflect functional relationship between the mitochondrial and nuclear genomes

Exophiala oligosperma involved in a refractory chronic rhinosinusitis.

Contains fulltext : 124309.pdf (Publisher’s version ) (Open Access)Fungal rhinosinusitis refers to a wide variety of conditions caused by fungal infections of the paranasal sinuses. Allergic fungal rhinosinusitis and sinus fungus balls are mostly noted in healthy individuals. Aspergillus species are supposed to be the most common etiologic agents of the disorder, but melanized fungi also occur, and these potentially are able to lead to fatal dissemination into brain parenchyma. We report on a case of fungus ball in a 20-year-old female with refractory chronic rhinosinusitis (RCRS) and bronchial asthma due to the black yeast Exophiala oligosperma which was confirmed by mycological and molecular (sequences of ITS rDNA) investigations. Exophiala oligosperma has previously not been reported to cause fungus balls or invasive fungal rhinosinusitis. Patient underwent functional endoscopic sinusitis surgery and the hypertrophic mucosa was removed completely. Without antifungal therapy, successful cure was achieved after spray therapy with corticosteroids for 1 month, without any relapse after a 6 month-follow up.01 maart 201

Zoonotic Tuberculosis: A Neglected Disease in the Middle East and North Africa (MENA) Region

Mycobacterium bovis is the etiologic agent of bovine tuberculosis (BTB), a serious infectious disease in both humans and animals. BTB is a zoonotic disease primarily affecting cattle and occasionally humans infected through close contact with infected hosts or the consumption of unpasteurized dairy products. Zoonotic tuberculosis is strongly associated with poverty and poor hygiene, and low- and middle-income countries bear the brunt of the disease. BTB has been increasingly recognized as a growing public health threat in developing countries. However, the lack of effective surveillance programs in many of these countries poses a barrier to accurately determining the true burden of this disease. Additionally, the control of BTB is threatened by the emergence of drug-resistant strains that affect the effectiveness of current treatment regimens. Here, we analyzed current trends in the epidemiology of the disease as well as the antimicrobial susceptibility patterns of M. bovis in the Middle East and North Africa (MENA) region, a region that includes several developing countries. Following PRISMA guidelines, a total of 90 studies conducted in the MENA region were selected. Our findings revealed that the prevalence of BTB among humans and cattle varied significantly according to the population size and country in the MENA region. Most of the available studies were based on culture and/or PCR strategies and were published without including data on antimicrobial resistance and molecular typing. Our findings highlighted the paramount need for the use of appropriate diagnostic tools and the implementation of sustainable control measures, especially at the human/animal interface, in the MENA region