Metabolic profile changes in the testes of mice with streptozotocin-induced type 1 diabetes mellitus

Contrary to the traditional view, recent studies suggest that diabetes mellitus has an adverse influence on male reproductive function. Our aim was to determine the effect of diabetes on the testicular environment by identifying and then assessing perturbations in small molecule metabolites. Testes were obtained from control and streptozotocin-induced diabetic C57BL/6 mice, 2, 4 and 8 weeks post-treatment. Diabetic status was confirmed by glycated haemoglobin, non-fasting blood glucose, physiological condition and body weight. A novel extraction procedure was utilized to obtain protein free, low-molecular weight, water soluble extracts which were then assessed using H-1 nuclear magnetic resonance spectroscopy. Principal component analysis of the derived profiles was used to classify any variations, and specific metabolites were identified based on their spectral pattern. Characteristic metabolite profiles were identified for control and type 1 diabetic animals with the most distinctive being from mice with the largest physical deterioration and loss of body weight. Eight streptozotocin-treated animals did not develop diabetes and displayed profiles similar to controls. Diabetic mice had decreases in creatine, choline and carnitine and increases in lactate, alanine and myo-inositol. Betaine levels were found to be increased in the majority of diabetic mice but decreased in a few animals with severe loss of body weight and physical condition. The association between perturbations in a number of small molecule metabolites known to be influential in sperm function, with diabetic status and physiological condition, adds further impetus to the proposal that diabetes influences important spermatogenic pathways and mechanisms in a subtle and previously unrecognized manner.

After the Party the Hangover?: An Analysis of ‘Post-Celtic Tiger’ Ireland in the Light of the February 2011 elections’

The election of February 2011 was dominated by the International Monetary Fund/European Central Bank bailout of November 2010, the state of the public finances, the ongoing Irish banking crisis, and the disastrous state of the economy with rising unemployment, emigration and collapsing international competiveness. After years of phenomenal economic growth (at least as measured by orthodox economic measurements such as gross domestic product (GDP) and foreign direct investment), known as the 'Celtic Tiger‘, during which a bloated construction industry accounted for a quarter of GDP and Irish banks sank nearly a third of their lending in construction projects, Ireland has entered a 'post-Celtic Tiger‘ era. This article offers a critical analysis outlining some political, economic and cultural issues of this election as heralding a decisive stage in the 'post-Celtic Tiger' development of the Republic of Ireland, and suggests that what is required at this present historical moment is that a different development model be articulated by the Irish state and wider society.

Bridging Jeffrey's Rule, AGM Revision and Dempster Conditioning in the Theory of Evidence

Belief revision characterizes the process of revising an agent’s beliefs when receiving new evidence. In the field of artificial intelligence, revision strategies have been extensively studied in the context of logic-based formalisms and probability kinematics. However, so far there is not much literature on this topic in evidence theory. In contrast, combination rules proposed so far in the theory of evidence, especially Dempster rule, are symmetric. They rely on a basic assumption, that is, pieces of evidence being combined are considered to be on a par, i.e. play the same role. When one source of evidence is less reliable than another, it is possible to discount it and then a symmetric combination operation
is still used. In the case of revision, the idea is to let prior knowledge of an agent be altered by some input information. The change problem is thus intrinsically asymmetric. Assuming the input information is reliable, it should be retained whilst the prior information should be changed minimally to that effect. To deal with this issue, this paper defines the notion of revision for the theory of evidence in such a way as to bring together probabilistic and logical views. Several revision rules previously proposed are reviewed and we advocate one of them as better corresponding to the idea of revision. It is extended to cope with inconsistency between prior and input information. It reduces to Dempster
rule of combination, just like revision in the sense of Alchourron, Gardenfors, and Makinson (AGM) reduces to expansion, when the input is strongly consistent with the prior belief function. Properties of this revision rule are also investigated and it is shown to generalize Jeffrey’s rule of updating, Dempster rule of conditioning and a form of AGM revision.

Role of charge in the radioprotection of E. coli by thiols.

The role of net charge (Z) of thiols in their ability to radioprotect cells has been investigated in a glutathione (GSH)-deficient strain of E. coli. This strain, 7, is deficient in the enzyme gamma-glutamylcysteine synthetase and allows the effects of added low molecular weight thiols to be studied. Using the gas explosion system it is possible to measure the chemical repair of the free-radical precursors of lethal lesions by thiols in intact cells. The first-order chemical repair rate in strain 7 is 280s(-1) in comparison with 1100s(-1) in the wild-type strain 1157. From the measured difference in the intracellular concentration of GSH between the wild-type and the mutant, this gives a second-order repair rate, k(r)'s of 1.23 +/- 0.3 X 10(5) dm(3)mol(-1)s(-1). Measurement of intracellular thiol levels after addition of various low molecular weight thiols showed that uptake was rapid, leading to stable thiol levels within 1 min. The ratios of the intracellular to extracellular concentrations (C-in/C-out) were 0.74 for 3-mercaptopropionic acid (Z=-1), 0.56 for 2-mercaptoethanol (Z=0), 1.47 for cysteamine (Z=+1) and 1.04 for WR1065 (Z=+2). The k(r)'s for these thiols were 1.3 +/- 0.5 X 10(5) dm(3)mol(-1)s(-1) for 30-mercaptopropionic acid, 3.3 +/- 1.6 x 10(5) dm(3)mol(-1)s(-1) for 2-mercaptoethanol, 3.9 +/- 1.1 X 10(5) dm(3)mol(-1)s(-1) for cysteamine and 2.7 +/- 1.1 X 10(6) dm(3)mol(-1)s(-1) for WR1065. These are lower and increase less with charge than previously published values for chemical repair in isolated pBR322 DNA, probably because of the association of nucleoproteins and polyamines with the cellular DNA of E. coli. However, the approximate three-fold increase in k(r) per unit increase in Z shows that the counter-ion condensation and co-ion depletion are important in determining the effectiveness of charged thiols in the radioprotection of E. coli.

Transfusion in the management of patients with megaloblastic anaemia

Transfusion has been associated with significant morbidity and mortality in megaloblastic anaemia (MA). This retrospective study was undertaken to examine the usefulness of transfusion in the management of MA. Fifty-two patients with MA were identified. Of the 20 transfused patients 13 were treated with diuretics and six with potassium supplements. The mean haemoglobin (Hb) of the transfused group was 6.5 g/dl (range 4.8-10.4 g/dl), and of the 32 non-transfused patients 10.5 g/dl (range 5.6-17.0 g/dl). The Hb and packed cell volume (PCV) were significantly lower in the transfused group. Only two of 32 non-transfused group were given potassium supplements. In this small group of patients with MA, transfusion appeared to be safe and no complications of transfusion were identified. However, advice was not being followed. We would suggest that, although transfusion has a minor role in the management of MA, consideration must be given to the general hazards of transfusion.