The comparison of sample extraction procedures for the determination of cations in soil by IC and ICP-AES

This paper presents the extraction of cations from a soil sample, type ranker on serpentinite, in deionized water, by use of three different extraction techniques. The first extraction technique included the use of a rotary mixer, the second technique involved the use of a microwave digestion system with different extraction temperatures, and the third technique employed an ultrasonic bath with different extraction times. Ion chromatography was used for determining the concentration of Li, Na, K, Ca, Mg and ammonium ions in soil extracts with subsequent determination of concentrations for all cations, except for ammonium ion extraction, conducted by Inductively Coupled Plasma-Atomic Emission Spectrometry. The results of cation extractions showed that microwave assisted extraction was most efficient for the Li, Na, K, Ca, Mg, Co, Mn, Ni, Pb and ammonium ions. Use of a rotary mixer for extraction was most efficient for Cd and Zn ions, while use of ultrasound bath was most efficient for Cr, Cu, Fe and Al ions. Several times higher amount of cations extracted by the most efficient, compared to the second best technique, under optimal conditions, were noticed in the case of: Ca, Mg, Co, Mn, Fe, Al, and Zn ions

Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience

IntroductionPeptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment.MethodologyWe retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups.ResultsA total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively.ConclusionThe study’s results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Clinical Usefulness of 99mTc-HYNIC-TOC and 131I-MIBG Scintigraphy in the Evaluation of Adrenal Tumors

Disorders and morphological abnormalities affecting the adrenal gland, could lead to profound clinical consequences, owing to its biochemical structure-activity and morphological characteristics

Voltammetric Behaviour and Determination of 8-Hydroxyquinoline Using a Glassy Carbon Paste Electrode and the Theoretical Study of its Electrochemical Oxidation Mechanism

The 8-Hydroxyquinoline (8HQ) oxidation process has been investigated by Cyclic Voltammetry using a Glassy Carbon Paste Electrode (GCPE) as a working electrode. The theoretical study of the mechanism of electrochemical oxidation of 8HQ has been based on the AM1 semi-empirical quantum chemical computations of the heats of formation of the reaction intermediates, taking into account the influence of pH and solvation effects. We proposed that a two-electron irreversible process, controlled by diffusion of electroactive species, is responsible for an oxidation peak of 8HQ that appears in all cyclic voltammograms recorded on a clean electrode in the solutions of pH in the range 2-12 with a supporting electrolyte of Britton-Robinson Buffer/methanol. A single-electron oxidation of 8HQ leads, depending on pH, to the formation of various free radical species that combine to make dimers which, after being oxidized once more, give quinonoid-type compounds. Recording continuous cyclic voltammograms on the GCPE, pre-peaks appear as a consequence of dimer and quinonoid compounds formation. By applying Differential Pulse Voltammetry for 8HQ determination it was calculated that the limit of detection was 5.2x10(-8) mol/L. For more sensitive quantitative determination of the investigated substance Adsorptive Stripping Differential Pulse Voltammery can be used since it was found that after 300s-deposition time at 0.0 V vs. Saturated Calomel Electrode, a 2.1 times higher peak current than without deposition was obtained

Voltammetric Behaviour and Determination of 8-Hydroxyquinoline Using a Glassy Carbon Paste Electrode and the Theoretical Study of its Electrochemical Oxidation Mechanism

The 8-Hydroxyquinoline (8HQ) oxidation process has been investigated by Cyclic Voltammetry using a Glassy Carbon Paste Electrode (GCPE) as a working electrode. The theoretical study of the mechanism of electrochemical oxidation of 8HQ has been based on the AM1 semi-empirical quantum chemical computations of the heats of formation of the reaction intermediates, taking into account the influence of pH and solvation effects. We proposed that a two-electron irreversible process, controlled by diffusion of electroactive species, is responsible for an oxidation peak of 8HQ that appears in all cyclic voltammograms recorded on a clean electrode in the solutions of pH in the range 2-12 with a supporting electrolyte of Britton-Robinson Buffer/methanol. A single-electron oxidation of 8HQ leads, depending on pH, to the formation of various free radical species that combine to make dimers which, after being oxidized once more, give quinonoid-type compounds. Recording continuous cyclic voltammograms on the GCPE, pre-peaks appear as a consequence of dimer and quinonoid compounds formation. By applying Differential Pulse Voltammetry for 8HQ determination it was calculated that the limit of detection was 5.2x10(-8) mol/L. For more sensitive quantitative determination of the investigated substance Adsorptive Stripping Differential Pulse Voltammery can be used since it was found that after 300s-deposition time at 0.0 V vs. Saturated Calomel Electrode, a 2.1 times higher peak current than without deposition was obtained

An Integrative in Silico Drug Repurposing Approach for Identification of Potential Inhibitors of SARS-CoV-2 Main Protease

Aims: An infectious disease (COVID-19) caused by the coronavirus SARS-CoV-2 emerged in Wuhan, China in December 2019. Currently, SARS-CoV-2 infected more than 9 million people and caused more than 450 000 deaths. Considering the urgent need for novel therapeutics, drug repurposing approach might offer rapid solutions comparing to de novo drug design. In this study, we investigated an integrative in silico drug repurposing approach as a valuable tool for rapid selection of potential candidates against SARS-CoV-2 Main Protease (Mpro).Main methods: To screen FDA-approved drugs, we designed an integrative in silico drug repurposing approach implementing structure-based molecular modelling techniques, physiologically-based pharmacokinetic (PBPK) modelling of drugs disposition and data-mining analysis of drug-gene-COVID-19 association.Key findings: Through the presented approach, 43 candidates with potential inhibitory effect on Mpro were selected and further evaluated according to the predictions of tissue disposition, drug-gene-COVID-19 associations and potential pleiotropic effects. We singled out 9 FDA approved drugs as the most promising for their profiling in COVID-19 drug discovery campaigns. Our results were in agreement with current experimental findings, which validate the applied integrative approach and may support clinical decisions for a novel epidemic wave of COVID-19.Significance: To the best of our knowledge, this is the first integrative in silico repurposing study for COVID-19 with a clear advantage in linking structure-based molecular modeling of Mpro inhibitors with predictions of tissue disposition, drug-gene-COVID-19 associations and prediction of pleiotropic effects of selected candidates.</div