Synthesis, characterization and antimicrobial activities of some 5-bromouracilmetal ion complexes

Six new complexes, [Mn(Br-U)2(H2O)2]×4H2O (1), [Cd(Br-U)2]×2H2O (2), [Cu(Br-U)2(H2O)2]×2H2O (3), [Co(Br-U)2(H2O)2]×4H2O (4), [Ni(Br-U)2(H2O)2]×4H2O (5) and [Ag(Br-U)(Br-U-H)]×2(H2O) (6)  were prepared by the reaction of 5-bromoouracil with MnCl2·4H2O, CdCl2·2.5H2O, CuSO4·5H2O, (CH3COO)2Co·4H2O, (CH3COO)2Ni·4H2O and AgNO3 respectively. The complexes were characterized by melting point, elemental microanalyses, IR and 1H NMR spectroscopy. The obtained data indicated that the ligand interacted with the metal ions in its mononegatively charged enol form in a bidentate fashion. Thermogravimetric analyses (TGA and DTG) were also carried out. The data obtained agreed well the proposed structures and showed that the complexes were finally decomposed to the corresponding metal or metal oxide. The ligand and its metal-ion complexes were tested for their antimicrobial activities against four bacterial strains (B. subtillis, S. aureus, E. coli and P. aeruginosa) by the agar-well diffusion technique using DMSO as a solvent. The obtained data showed that the complexes were more potent antimicrobial agents than the parent ligand.               KEY WORDS: 5-Bromoouracil–M2+ complexes, IR, Thermal analyses, 1H NMR, Antimicrobial activity Bull. Chem. Soc. Ethiop. 2019, 33(2), 255-268.DOI: https://dx.doi.org/10.4314/bcse.v33i2.

The correlation of in vitro antioxidant potentials with the various biochemical responses of salinized basil leaves

One of the environmental sustainability issues is salinity. Basil seedlings (Ocimum basilicum L.) were treated using NaCl solutions of three different concentrations prepared using irrigation (40, 80, and 130 mM), and various biochemical analyses were performed on basil leaves. The number of leaves, leaf area, moisture, weights, and MDA content of basil decreased significantly as salinity levels increased from 40 to 130 mM; however, dry matter increased. As well, the current study investigated a significant increase in osmolytes (including total soluble sugars and proline) and Na+ contents. The highest activities of CAT and SOD in the leaf tissues of basil were recorded after treatment with 130 mM NaCl, whereas the polyphenol and total flavonoid contents were negatively influenced.  On the other hand, the highest ABTS scavenging activity was observed in the 40 mM-treated leaves at a concentration of 1000 µg/mL; however, the DPPH scavenging potential increased significantly in the 80 mM-treated leaves at 3000 µg/mL. Furthermore, the correlation between in vitro antioxidant potentials and biochemical responses was described. A strong correlation was identified between the in vitro antioxidant capacities of salinized O. basilicum leaves and SOD activity, total flavonoids, and the presence of phenolic acids, particularly p-hydroxybenzoic and o-coumaric acids at various concentrations. As a result, this is the first study to explain how basil may resist salinity by producing specific antioxidant compounds; therefore, our research recommends use of salinity issue to obtain a better plant material for producing dietary supplements or herbal drugs

High-fat, sucrose and salt-rich diet during rat spermatogenesis lead to the development of chronic kidney disease in the female offspring of the F2 generation

Effects of feeding male rats during spermatogenesis a high-fat, high-sucrose and high-salt diet (HFSSD) over two generations (F0 and F1) on renal outcomes are unknown. Male F0 and F1 rats were fed either control diet (F0CD+F1CD) or HFSSD (F0HD+F1HD). The outcomes were glomerular filtration rate and urinary albumin excretion in F1 and F2 offspring. If both outcomes were altered a morphological and molecular assessment was done. F2 offspring of both sexes had a decreased GFR. However, increased urinary albumin excretion was only observed in female F2 F0HD+F1HD offspring compared with controls. F0HD+F1HD female F2 offspring developed glomerulosclerosis (+31%; p < .01) and increased renal interstitial fibrosis (+52%; p < .05). RNA sequencing followed by qRT-PCR validation showed that four genes (Enpp6, Tmem144, Cd300lf, and Actr3b) were differentially regulated in the kidneys of female F2 offspring. lncRNA XR-146683.1 expression decreased in female F0HD+F1HD F2 offspring and its expression was (r = 0.44, p = .027) correlated with the expression of Tmem144. Methylation of CpG islands in the promoter region of the Cd300lf gene was increased (p = .001) in female F2 F0HD+F1HD offspring compared to controls. Promoter CpG island methylation rate of Cd300lf was inversely correlated with Cd300lf mRNA expression in F2 female offspring (r = −0.483, p = .012). Cd300lf mRNA expression was inversely correlated with the urinary albumin-to-creatinine ratio in female F2 offspring (r = −0.588, p = .005). Paternal pre-conceptional unhealthy diet given for two generations predispose female F2 offspring to chronic kidney disease due to epigenetic alterations of renal gene expression. Particularly, Cd300lf gene promotor methylation was inversely associated with Cd300lf mRNA expression and Cd300lf mRNA expression itself was inversely associated with urinary albumin excretion in F2 female offspring whose fathers and grandfathers got a pre-conceptional unhealthy diet

Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler® 150 and 300 μg

Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose

An ATP and Oxalate Generating Variant Tricarboxylic Acid Cycle Counters Aluminum Toxicity in Pseudomonas fluorescens

Although the tricarboxylic acid (TCA) cycle is essential in almost all aerobic organisms, its precise modulation and integration in global cellular metabolism is not fully understood. Here, we report on an alternative TCA cycle uniquely aimed at generating ATP and oxalate, two metabolites critical for the survival of Pseudomonas fluorescens. The upregulation of isocitrate lyase (ICL) and acylating glyoxylate dehydrogenase (AGODH) led to the enhanced synthesis of oxalate, a dicarboxylic acid involved in the immobilization of aluminum (Al). The increased activity of succinyl-CoA synthetase (SCS) and oxalate CoA-transferase (OCT) in the Al-stressed cells afforded an effective route to ATP synthesis from oxalyl-CoA via substrate level phosphorylation. This modified TCA cycle with diminished efficacy in NADH production and decreased CO2-evolving capacity, orchestrates the synthesis of oxalate, NADPH, and ATP, ingredients pivotal to the survival of P. fluorescens in an Al environment. The channeling of succinyl-CoA towards ATP formation may be an important function of the TCA cycle during anaerobiosis, Fe starvation and O2-limited conditions

Mild hypothermia delays the development of stone heart from untreated sustained ventricular fibrillation - a cardiovascular magnetic resonance study

<p>Abstract</p> <p>Background</p> <p>'Stone heart' resulting from ischemic contracture of the myocardium, precludes successful resuscitation from ventricular fibrillation (VF). We hypothesized that mild hypothermia might slow the progression to stone heart.</p> <p>Methods</p> <p>Fourteen swine (27 ± 1 kg) were randomized to normothermia (group I; n = 6) or hypothermia groups (group II; n = 8). Mild hypothermia (34 ± 2°C) was induced with ice packs prior to VF induction. The LV and right ventricular (RV) cross-sectional areas were followed by cardiovascular magnetic resonance until the development of stone heart. A commercial 1.5T GE Signa NV-CV/i scanner was used. Complete anatomic coverage of the heart was acquired using a steady-state free precession (SSFP) pulse sequence gated at baseline prior to VF onset. Un-gated SSFP images were obtained serially after VF induction. The ventricular endocardium was manually traced and LV and RV volumes were calculated at each time point.</p> <p>Results</p> <p>In group I, the LV was dilated compared to baseline at 5 minutes after VF and this remained for 20 minutes. Stone heart, arbitrarily defined as LV volume <1/3 of baseline at the onset of VF, occurred at 29 ± 3 minutes. In group II, there was less early dilation of the LV (p < 0.05) and the development of stone heart was delayed to 52 ± 4 minutes after onset of VF (P < 0.001).</p> <p>Conclusions</p> <p>In this closed-chest swine model of prolonged untreated VF, hypothermia reduced the early LV dilatation and importantly, delayed the onset of stone heart thereby extending a known, morphologic limit of resuscitability.</p

A pilot study using Tissue Velocity Ultrasound Imaging (TVI) to assess muscle activity pattern in patients with chronic trapezius myalgia

<p>Abstract</p> <p>Background</p> <p>Different research techniques indicate alterations in muscle tissue and in neuromuscular control of aching muscles in patients with chronic localized pain. Ultrasound can be used for analysis of muscle tissue dynamics in clinical practice.</p> <p>Aim</p> <p>This study introduces a new muscle tissue sensitive ultrasound technique in order to provide a new methodology for providing a description of local muscle changes. This method is applied to investigate trapezius muscle tissue response – especially with respect to specific regional deformation and deformation rates – during concentric shoulder elevation in patients with chronic trapezius myalgia and healthy controls before and after pain provocation.</p> <p>Methods</p> <p>Patients with trapezius myalgia and healthy controls were analyzed using an ultrasound system equipped with tissue velocity imaging (TVI). The patients performed a standardized 3-cm concentric shoulder elevation before and after pain provocation/exercise at a standardized elevation tempo (30 bpm). A standardized region of interest (ROI), an ellipsis with a size that captures the upper and lower fascia of the trapezius muscle (4 cm width) at rest, was placed in the first frame of the loop registration of the elevation. The ROI was re-anchored frame by frame following the same anatomical landmark in the basal fascia during all frames of the concentric phase. In cardiac measurement, tissue velocities are measured in the axial projection towards and against the probe where red colour represents shortening and red lengthening. In the case of measuring the trapezius muscle, tissue deformation measurements are made orthogonally, thus, indirectly. Based on the assumption of muscle volume incompressibility, blue represents tissue contraction and red relaxation. Within the ROI, two variables were calculated as a function of time: <it>deformation </it>and <it>deformation rate</it>. Hereafter, max, mean, and quadratic mean values (RMS) of each variable were calculated and compared before and after pain provocation/exercise.</p> <p>Results</p> <p>This new methodology seems valuable when looking at local muscle changes and studying the mechanism behind chronic muscle pain. The univariate analyses indicate that patients with chronic trapezius myalgia after pain provocation due to exercise at group level showed decreased strain and unchanged strain rate while healthy controls had unchanged strain and increased strain rate. However, the multivariate analysis indicates that most patients showed lower levels according to both strain and strain rate after exercise compared to most controls.</p> <p>Conclusion</p> <p>Tissue velocity imaging can help describe musculoskeletal tissue activity and dynamics in patients with chronic pain conditions. An altered muscle tissue dynamic after pain provocation/exercise among the majority of trapezius myalgia patients compared with the healthy controls was found.</p

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Phenotype Enhancement Screen of a Regulatory spx Mutant Unveils a Role for the ytpQ Gene in the Control of Iron Homeostasis

Spx is a global regulator of genes that are induced by disulfide stress in Bacillus subtilis. The regulon that it governs is comprised of over 120 genes based on microarray analysis, although it is not known how many of these are under direct Spx control. Most of the Spx-regulated genes (SRGs) are of unknown function, but many encode products that are conserved in low %GC Gram-positive bacteria. Using a gene-disruption library of B. subtilis genomic mutations, the SRGs were screened for phenotypes related to Spx-controlled activities, such as poor growth in minimal medium and sensitivity to methyglyoxal, but nearly all of the SRG mutations showed little if any phenotype. To uncover SRG function, the mutations were rescreened in an spx mutant background to determine which mutant SRG allele would enhance the spx mutant phenotype. One of the SRGs, ytpQ was the site of a mutation that, when combined with an spx null mutation, elevated the severity of the Spx mutant phenotype, as shown by reduced growth in a minimal medium and by hypersensitivity to methyglyoxal. The ytpQ mutant showed elevated oxidative protein damage when exposed to methylglyoxal, and reduced growth rate in liquid culture. Proteomic and transcriptomic data indicated that the ytpQ mutation caused the derepression of the Fur and PerR regulons of B. subtilis. Our study suggests that the ytpQ gene, encoding a conserved DUF1444 protein, functions directly or indirectly in iron homeostasis. The ytpQ mutant phenotype mimics that of a fur mutation, suggesting a condition of low cellular iron. In vitro transcription analysis indicated that Spx stimulates transcription from the ytpPQR operon within which the ytpQ gene resides. The work uncovers a link between Spx and control of iron homeostasis

Food Policy Development in the Australian State of Victoria: A Case Study of the Food Alliance

This article explores the development of a food policy body called the Food Alliance and the role of the organization in encouraging the development of food policy that integrates health and ecological issues. The Food Alliance is located within the Australian state of Victoria. A policy triangle is used as a framework to describe and analyse the work of the Food Alliance. Lessons are drawn about effective strategies for influencing integrated food policy. This occurs in a context where food policy typically favours powerful industry and agricultural interests and where relationships between the health and environmental sectors are in their infancy. The implications for planning and organizing a state-wide food policy are explored from the perspective of policy and the ways in which this can be influenced through working with key stakeholders