Pulmonary Hypertension Is a Frequent Event in Patients with Chronic Myeloid Leukemia Treated with Tyrosine Kinase Inhibitors

Poster presented at American Society of Clinical Oncology in Chicago Illinois. Background: Tyrosine kinase inhibitors (TKI) are the current standard therapy for patients with chronic myeloid leukemia (CML). Fluid retention and pleural effusions have been reported in patients treated with TKIs, particularly with dasatinib. Although TKIs have been shown to reverse pulmonary hypertension (PH) in animal models, there have been some reports of development of reversible PH with dasatinib. Methods: We conducted a retrospective analysis on 401 patients diagnosed with CML in chronic phase (CP) who were treated with TKIs (imatinib, dasatinib, or nilotinib) as initial therapy for CML and had a transthoracic echocardiogram (TTE) done at some point during the course of therapy. PH was diagnosed if the patient had an estimated right ventricular systolic pressure (RVSP) of 35 mm Hg or greater. Secondary causes of PH (systolic or diastolic dysfunction on TTE, chronic obstructive pulmonary diseases [COPD], obstructive sleep apnea [OSA] and pulmonary embolism) were investigated during chart review. Results: Twenty (23%) out of 87 patients had evidence of PH by TTE; median age 57 years, with 46% being males. Six pts (30%) received nilotinib 400mg twice daily, 4 (20%) patients had imatinib (400mg; n=1, 600mg; n=1 and 800mg daily; n=2), and 10 (50%) patients received dasatinib (dose varied 40-140mg daily). Five (25%) patients had coronary artery disease, 9 (45%) had systemic hypertension, 2 (10%) had COPD and 3 (15%) had OSA. Thirteen pts had serial TTE to compare the progression of PH including 6 (7%) who had a TTE prior to starting TKI. Among these 13 pts with serial TTE, 7 had rising RVSP with one patient having mild global hypokinesia, another with diastolic dysfunction and another with OSA. Four of those 7 patients had normal RVSP on their TTE prior to starting therapy. Six other pts had improvement in the RVSP on serial TTE, 4 of them with systemic hypertension. Two of those 6 patients had elevated RVSP on their TTE prior to starting therapy; one pt had no change. Eleven patients had pleural effusions (7 dasatinib, 3 imatinib, 1 nilotinib) associated with PH. Conclusions: TKI therapy is occasionally associated with development of PH, but RVSP may improve spontaneously in some patients. A prospective study is needed to further investigate the relationship between TKIs and the development of PH

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

Some microbial treatments against the tomato leaf miner; Tuta absoluta (Merick) under natural field conditions

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Synthesis and spectroscopic studies of metal complexes formed in the reaction of metal ions with urea at high temperature

Urea reacts with PtCl2, H2[PtCl6]·6H2O, H2[IrCl6] and Ni(CH3CO2)2 in aqueous solution at high temperature (60-80 °C) yielding [PtCl2(Urea)]·2H2O (1), (NH4)2[PtCl6] (2), (NH4)2[IrCl6]·H2O (3) and [Ni2(OH)2(NCO)2(H2O)2] (4) complexes, respectively. In complex 1, urea coordinates to Pt(II) as a neutral bidentate ligand via amido nitrogen atoms. In complexes 2, 3 and 4 it seems that the coordinated urea molecules decompose during the reaction at high temperature and a variety of reaction products are obtained. All complexes were isolated in moderate yields as dark green (1), yellow (2), pale brown (3) and faint green (4) precipitates, respectively. The reaction products were characterized by their microanalysis, IR, 1H and 13C NMR spectra as well as thermal analysis. General mechanisms describing the formation of these complexes were suggested.Scopu

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

Effect of fennel (Foeniculum vulgare) on some pathophysiological alterations in induced hyperlipidemic male Albino Rats

Obesity alters lipid profile, blood glucose, liver enzymes, oxidative stress, and hormonal balance. Fennel has shown anti-obesity effects in preliminary studies, but its role in ameliorative metabolic complications of obesity needs further research. This study assessed the provisional influences of fennel extract against high-fat diet-provoked metabolic deviations in rats. Forty male albino rats were allocated into standard diet control, obese control, low dose fennel (100 mg/kg) and high dose fennel (300 mg/kg) groups. Obesity was triggered by 4 weeks of high-fat nourishment. Fennel extract was applied orally for 6 weeks. Parameters considered were body weight, lipid profile, blood glucose, liver enzymes, anti-oxidant status, thyroid hormones, leptin, and hepatic insulin receptor gene expression. Fennel significantly diminished body weight, total cholesterol, triglycerides, LDL-cholesterol, liver enzymes, glucose, and leptin while increasing HDL-cholesterol, anti-oxidant enzymes, and thyroid stimulating hormone compared to obese controls. Histological examination has shown alleviation of fat accumulation and intracellular changes in the liver. Insulin receptor gene expression was also significantly increased by fennel extract. This study demonstrated that fennel extract reverses obesity-induced metabolic syndrome, oxidative stress, endocrine disruption, and histopathological change in the liver of rats. The hypolipidemic, hypoglycemic, anti-oxidant, and hepatoprotective properties of fennel may be beneficial in managing obesity-associated metabolic complications

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

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