Degradation of glucose-1-C14 and a possible new step in the mechanism of fermentation

The availability of glucose-1-c14 has permitted the verification of a scheme of glucose degradation applied to sugars formed in photosynthesis to determine the distribution of isotopic carbon within the sugar. As a result of the present investigation, there appears to be a second, though minor, pathway of fermentation of the test organism, Lactobacillus casei

Hyaluronidase recruits mesenchymal-like cells to the lung and ameliorates fibrosis

Hyaluronidases (HYALs) comprise a group of enzymes that degrade hyaluronic acid (HA). In this report, we reveal that a single intranasal inoculation of HYAL induces an increase in mononuclear cells within the bronchoalveolar space demonstrating a mesenchymal-like phenotype, expressing stem cell antigen-1 (SCA-1), CD44 and CD73 but not CD34, CD45, CD3, CD4, CD8 or CD19. This influx of mesenchymal stem cell (MSC)-like cells was dependent on leukotriene production within the lung parenchyma. These findings prompted experiments demonstrating that HYAL treatment potently blocked bleomycin-induced lung injury and fibrosis while decreasing transforming growth factor (TGF)-β production and collagen deposition. These data suggest that HYAL is a novel and promising tool to use autologous MSC-like cells in the treatment of pulmonary fibrosis

A prospective observational study of bacteraemia in adults admitted to an urban Mozambican hospital

Background. Bacteraemia is a common cause of fever among patients presenting to hospitals in  sub-Saharan Africa. The worldwide rise of antibiotic resistance makes empirical therapy increasingly  difficult, especially in resource-limited settings.Objectives. To describe the incidence of bacteraemia in febrile adults presenting to Maputo Central Hospital (MCH), an urban referral hospital in the capital of Mozambique, and characterise the causative  organisms and antibiotic susceptibilities. We aimed to describe the antibiotic prescribing habits of local doctors, to identify areas for quality improvement.Methods. Inclusion criteria were: (i) .18 years of age; (ii) axillary temperature .38‹C or .35‹C; (iii) admission to MCH medical wards in the past 24 hours; and (iv) no receipt of antibiotics as an inpatient. Blood cultures were drawn from enrolled patients and incubated using the BacT/Alert automated system (bioMerieux, France). Antibiotic susceptibilities were tested using the Kirby-Bauer disc diffusion method.Results. Of the 841 patients enrolled, 63 (7.5%) had a bloodstream infection. The most common isolates were Staphylococcus aureus, Escherichia coli, and non-typhoidal Salmonella. Antibiotic resistance was common, with 20/59 (33.9%) of all bacterial isolates showing resistance to ceftriaxone, the broadest-spectrum antibiotic commonly available at MCH. Receipt of insufficiently broad empirical antibiotics was associated with poor in-hospital outcomes (odds ratio 8.05; 95% confidence interval 1.62 - 39.91;  p=0.04).Conclusion. This study highlights several opportunities for quality improvement, including educating doctors to have a higher index of suspicion for bacteraemia, improving local antibiotic guidelines,  improving communication between laboratory and doctors, and increasing the supply of some key antibiotics

The algebra of lexical semantics

Abstract. The current generative theory of the lexicon relies primar-ily on tools from formal language theory and mathematical logic. Here we describe how a different formal apparatus, taken from algebra and automata theory, resolves many of the known problems with the gener-ative lexicon. We develop a finite state theory of word meaning based on machines in the sense of Eilenberg [11], a formalism capable of de-scribing discrepancies between syntactic type (lexical category) and se-mantic type (number of arguments). This mechanism is compared both to the standard linguistic approaches and to the formalisms developed in AI/KR. 1 Problem Statement In developing a formal theory of lexicography our starting point will be the informal practice of lexicography, rather than the more immediately related for-mal theories of Artificial Intelligence (AI) and Knowledge Representation (KR). Lexicography is a relatively mature field, with centuries of work experience an

Variation at the NFATC2 Locus Increases the Risk of Thiazolidinedione-Induced Edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) Study

Objective: Thiazolidinediones are used to treat type 2 diabetes. Their use has been associated with peripheral edema and congestive heart failure - outcomes that may have a genetic etiology. Research Design and Methods: We genotyped 4,197 participants of the multiethnic DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) trial with a 50k single nucleotide polymorphisms (SNP) array, which captures ∼2000 cardiovascular, inflammatory, and metabolic genes. We tested 32,088 SNPs for an association with edema among Europeans who received rosiglitazone (n = 965). Results: One SNP, rs6123045, in NFATC2 was significantly associated with edema (odds ratio 1.89 [95% CI 1.47-2.42]; P = 5.32 × 10-7, corrected P = 0.017). Homozygous individuals had the highest edema rate (hazard ratio 2.89, P = 4.22 × 10-4) when compared with individuals homozygous for the protective allele, with heterozygous individuals having an intermediate risk. The interaction between the SNP and rosiglitazone for edema was significant (P = 7.68 × 10-3). Six SNPs in NFATC2 were significant in both Europeans and Latin Americans (P < 0.05). Conclusions: Genetic variation at the NFATC2 locus contributes to edema among individuals who receive rosiglitazone

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Formulacija i evaluacija monolitnih matriksnih polimernih filmova za transdermalnu isporuku nitrendipina

The objective of the present work was to develop a suitable transdermal drug delivery system for nitrendipine. Polymeric films of nitrendipine were prepared by the film casting technique (glass ring) on mercury substrate. They were evaluated for physicochemical parameters, in vitro release and ex vivo permeation (heat separated human epidermis). Release of the drug from the films followed anomalous transport (0.5 < n < 1). Polymeric combination containing Eudragit RL 100:PVP K 30 in 4:6 ratio showed the best results. Maximum drug release and skin permeability coefficient in 48 h were 85.8 % and 0.0142 cm h-1, respectively, in formulation C3 (Eudragit RL 100: Plasdone S 630; 4:6) and 88.0 % and 0.0155 cm h-1, respectively, in formulation D3 (Eudragit RL 100: PVP K 30; 4:6). FTIR and TLC studies indicated no drug and polymer interaction.Cilj rada bio je razvoj transdermalnog sustava nitrendipina. Polimerni filmovi nitrendipina pripravljeni su metodom lijevanja (stakleni prsten) na podlozi od žive. Ispitivani su fizičkokemijski parametri, in vitro oslobađanje i ex vivo permeacija (toplinom odvojena humana epiderma). Oslobađanje lijeka iz filmova slijedilo je anomalni transport (0,5 < n < 1). Najbolji rezultati postignuti su kombinacijom polimera Eudragit RL 100 i PVP K 30 u omjeru 4:6. Maksimalno oslobađanje ljekovite tvari i najbolji koeficijent permeacije kroz kožu tijekom 48 h bio je 85,8 %, odnosno 0,0142 cm h1 za formulaciju C3 (Eudragit RL 100 : Plasdone S 630; 4:6) i 88,0 %, odnosno 0,0155 cm h1 za formulaciju D3 (Eudragit RL 100 : PVP K 30; 4:6). FTIR i TLC ukazuju na to da nema interakcije između ljekovite tvari i polimera

Clostridium difficile ribotype diversity at six health care institutions in the United States

Capillary-based PCR ribotyping was used to quantify the presence/absence and relative abundance of 98 Clostridium difficile ribotypes from clinical cases of disease at health care institutions in six states of the United States. Regionally important ribotypes were identified, and institutions in close proximity did not necessarily share more ribotype diversity than institutions that were farther apart