Migration and Aggregation Behavior of Nickel and Iron in Low Grade Laterite Ore with New Additives

This study focused on the preparation of high-grade ferronickel concentrate, the behavior of efficient migration and the polymerization of ferronickel particles during reduction roasting, by adding calcium fluoride and a ferronickel concentrate to low-grade laterite ore from Yunnan. The effects of temperature, holding time, reductant content, ferronickel concentrate content and magnetic field intensity on the preparation of the ferronickel concentrate were studied and the optimum conditions were determined as follows: 30% ferronickel concentrate (metal Ni-4.68%, metal Fe-45.0%), 8% coal, 7% calcium fluoride, reduction temperature of 1250 °C, reduction time of 60 min and the intensity of magnetic separation is 150 mT. The proportion of nickel and iron in ferronickel concentrate was 88.7% (metal Ni-8.62%, metal Fe-80.1%), and the recovery efficiency of nickel and iron are 98.8% and 82.4%, respectively. X-ray diffraction and scanning electron microscopy indicated that ferronickel-concentrate, as an activating agent, improved the aggregation effect of ferronickel particles. The efficient migration and polymerization of ferronickel particles in the ore significantly increased the size of the ferronickel particles with additives, therefore a high-grade ferronickel concentrate was prepared, and the reduction and recovery efficiency of laterite nickel ore was improved.

Product Flexibility Strategy Under Supply and Demand Risk

Problem definition: With heightened global uncertainty, supply chain managers are under increasing pressure to craft strategies that accommodate both supply and demand risks. Although product flexibility is a well-understood strategy to accommodate risk, there is no clear guidance on the optimal flexibility configuration of a supply network that comprises both unreliable primary suppliers and reliable backup suppliers. Academic/practical relevance: Existing literature examines the value of flexibility with primary and backup suppliers independently. For a risk-neutral firm, research shows that (a) incorporating flexibility in a primary supplier by replacing two dedicated ones (in absence of backup supply) is always beneficial and that (b) adding flexibility to a reliable backup supplier (in absence of product flexibility in primary suppliers) is always valuable. It is unclear, however, how flexibility should be incorporated into a supply network with both unreliable primary suppliers and reliable backup suppliers. This research studies whether flexibility should be incorporated in a primary supplier, a backup supplier, or both. Methodology: We develop a normative model to analyze when flexibility benefits and when it hurts. Results: Compared with a base case of no flexibility, we prove that incorporating flexibility in either primary or backup suppliers is always beneficial. However, incorporating flexibility in both primary and backup suppliers can be counterproductive because the supply chain performance can decline with saturated flexibility, even if flexibility is costless. A key reason is that the risk-aggregation effect of consolidating flexibility in an unreliable supplier becomes more salient when flexibility is already embedded in a backup supplier. Managerial implications: This research refines the existing understanding of flexibility by illustrating that flexibility is not always beneficial. When there is a choice, a firm should prioritize incorporating flexibility in a reliable backup supplier.

Assessment of Platelet Reactivity and Inflammatory Markers in Coronary Artery Bypass Graft Patients Treated with Acetylsalicylic Acid with Flavonoid Supplementation

The recommended pharmacological therapy for patients with coronary artery disease (CAD) treated by coronary artery bypass grafting (CABG) is acetylsalicylic acid (ASA). To improve the antiplatelet effect, supplementation with flavonoids is also recommended. The aim of this study was to estimate anti-aggregation properties of diosmin, in combination with ASA, pre- and postoperatively and assess the relationship of this therapy with inflammatory processes in CAD patients undergoing CABG. The study patients (n = 26) took diosmin (1000 mg/day); the control patients (n = 27) took a placebo. The therapeutic period for taking diosmin was from at least 30 days before to 30 days after CABG. All patients also took 75 mg/day ASA. Platelet aggregation and IL-6, CRP, and fibrinogen concentrations were determined before and 30 days after surgery. Results showed that diosmin did not enhance the anti-aggregation effect of ASA at any assessment time. However, there was a stronger anti-aggregation effect 30 days after surgery that was diosmin independent and was associated with acute-phase markers in the postoperative period. Increased levels of inflammatory markers in the late phase of the postoperative period may provide an unfavorable prognostic factor in long-term follow-up, which should prompt the use of stronger antiplatelet therapy in patients after CABG.

Some Single-Valued Neutrosophic Uncertain Linguistic Maclaurin Symmetric Mean Operators and Their Application to Multiple-Attribute Decision Making

The Maclaurin symmetric mean (MSM) operator has a good aggregation effect. It can capture the relationships between multiple input parameters, and the neutrosophic uncertain linguistic numbers can well represent some indeterminate and incomplete information. In this paper, we combine the MSM operator with the singled-valued neutrosophic uncertain linguistic set and propose some MSM operators based on single-valued neutrosophic uncertain linguistic environment, such as single-valued neutrosophic uncertain linguistic Maclaurin symmetric mean(SVNULMSM) operator and single-valued neutrosophic uncertain linguistic generalized Maclaurin symmetric mean(SVNULGMSM) operator. First of all, according to the neutrosophic set and uncertain linguistic numbers, we propose the single-valued neutrosophic uncertain linguistic numbers and give some operating rules. Furthermore, considering the influence of attribute weight on the results, we introduce the weighted SVNULMSM operator and weighted SVNULGMSM operator. Then, we propose a method to deal with MSDM problems and give the specific steps to solve the problem. Finally, an investment example is used to verify the effectiveness of our method, and the superiority of the method is proved by comparing with other methods.

Comparative study of specific activity of rectal suppositories with clopidogrel

One of the most effective platelet antiaggregants is clopidogrel, inhibiting platelet activation by selectively binding adenosine diphosphate (ADP) with specific receptors. However, in a number of clinical situations it is necessary to have a pronounced antithrombotic effect in the shortest possible time which gives rise to interest in the transmucose use of the drug, in particular, rectal route. The theoretical preconditions for the development of a rectal administration of clopidogrel are based on the data that the anti-aggregation effect of a substance is carried out by its main metabolite formed after “first hepatic passage”, while clopidogrel itself in this aspect is inactive. On the base of complex physico-chemical, pharmaceutical, biopharmaceutical, rheological and microbiological investigations, the rational composition of clopidogrel rectal dosage form – suppository on a hydrophilic base to prevent atherothrombotic events in patients with myocardial infarction, acute coronary syndrome, ischemic stroke, peripheral arterial occlusion, is proposed by the employees of the Department of Technology of Medications of the Zaporizhzhia State Medical University. The aim of the work is to investigate the specific activity of rectal suppositories with clopidogrel. Materials and methods. Experimental suppositories with clopidogrel 0,075 g for rectal administration were used as the objects in pre-line studies. The ability of clopidogrel to reduce the inhibitory effect of ADP on adenylate cyclase activity and decrease the number of binding sites for 2-methylthio-ADP (analogue of ADP) without altering the receptor topography is used as a base of the method of comparative study of its specific activity in the rectal dosage form (suppository) and in comparison with the reference medication Plavix (SANOFI WINTHROP INDUSTRIE, France) in the tablet form. Studies were performed on white non-linear rats of different sexes with different mass 150–210 g, aged 3.5–5.0 months. Results. Statistically significant differences in the inhibition of induced platelet aggregation were registered after 6 hours of rectal administration of clopidogrel and gastric administration of the reference medication, indicating the effectiveness of the rectal applicative transmucosal route for this active pharmaceutical ingredient (API). On the 5th day of administration, inhibition of induced platelet aggregation significantly increased, and that is supported by literature on the cumulative effect of clopidogrel in daily life. When comparing the digital material of the table, it is obvious that the rectal administration of clopidogrel is more effective in comparison with oral route which is probably due to the rapid delivery of API to the liver and the formation of an active metabolite of clopidogrel inhibiting the induction and spontaneous aggregation of platelets in human’s and animal’s blood. Obtained data provide with sound arguments for development of rectal suppositories with clopidogrel because in clinical care faster achievement of an anti-aggregation effect in patients with acute coronary syndrome is the primary task of clinical pharmacology and pharmacy. Conclusions. Using the biochemical model of pathology, it was established that the applicative semisolid medication of clopidogrel in the form of rectal suppository exhibited inductive anti-aggregation activity and its administration didn’t reveal any side effects and undesirable events. Rectal suppositories with clopidogrel have been shown to exhibit faster reliable anti-aggregation effect in comparison with intragastric administration.

Novel serotonin 5-HT2A receptor antagonists derived from 4-phenylcyclohexane-5-spiro-and 5-methyl-5-phenyl-hydantoin, for use as potential antiplatelet agents

Background Antiplatelet drugs have been used in the treatment of acute coronary syndromes and for the prevention of recurrent events. Unfortunately, many patients remain resistant to the available antiplatelet treatment. Therefore, there is a clinical need to synthesize novel antiplatelet agents, which would be associated with different pathways of platelet aggregation, to develop an alternative or additional treatment for resistant patients. Recent studies have revealed that 5-HT2A receptor antagonists could constitute alternative antiplatelet therapy. Methods Based on the structures of the conventional 5-HT2A receptor ligands, two series of compounds with 4-phenylcyclohexane-5-spiro- or 5-methyl-5-phenyl-hydantoin core linked to various arylpiperazine moieties were synthesized and their affinity for 5-HT2A receptor was assessed. Further, we evaluated their antagonistic potency at 5-HT2A receptors using isolated rat aorta and cells expressing human 5-HT2A receptors. Finally, we studied their anti-aggregation effect and compared it with ketanserin and sarpogrelate, the reference 5-HT2A receptor antagonists. Moreover, the structure–activity relationships were studied following molecular docking to the 5-HT2A receptor model. Results Functional bioassays revealed some of the synthesized compounds to be moderate antagonists of 5-HT2A receptors. Among them, 13, 8-phenyl-3-(3-(4-phenylpiperazin-1-yl)propyl)-1,3-diazaspiro[4.5]decane-2,4-dione, inhibited collagen stimulated aggregation (IC50 = 27.3 μM) being more active than sarpogrelate (IC50 = 66.8 μM) and comparable with ketanserin (IC50 = 32.1 μM). Moreover, compounds 2–5, 9–11, 13, 14 inhibited 5-HT amplified, ADP- or collagen-induced aggregation. Conclusions Our study confirmed that the 5-HT2A antagonists effectively suppress platelet aggregation and remain an interesting option for the development of novel antiplatelet agents with an alternative mechanism of action.