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We give a simple and direct proof of necessary and sufficient conditions to have constant equilibrium prices in a simple Sraffa’s production model. We make some remarks on the linearity of the relation between profit rate and wage rate.

16 p.-9 fig.-9 tab.-1 graph. abst., Hybrid compounds containing structural fragments of the Rho kinase inhibitor fasudil and the NRF2 inducers caffeic and ferulic acids were designed with the aid of docking and molecular mechanics studies. Following the synthesis of the compounds using a peptide-coupling methodology, they were characterized for their ROCK2 inhibition, radical scavenging, effects on cell viability (MTT assay), and NRF2 induction (luciferase assay). One of the compounds (1d) was selected in view of its good multitarget profile and good tolerability. It was able to induce the NRF2 signature, promoting the expression of the antioxidant response enzymes HO-1 and NQO1, via a KEAP1-dependent mechanism. Analysis of mRNA and protein levels of the NRF2 pathway showed that 1d induced the NRF2 signature in control and SOD1-ALS lymphoblasts but not in sALS, where it was already increased in the basal state. These results show the therapeutic potential of this compound, especially for ALS patients with a SOD1 mutation., This work was supported by the Comunidad de Madrid (grant B2017/BMD-3813), MINECO (grant RTI2018-097662-B-I00 to J.C.M. and PID2019-105600RB-I00 to A.M. and I.L.-B), ISCiii CIBERNED (CB18/05/00040 to A.M. and Á.M.-R. and CB06/05/0089 to I.L.-B.), and Fundela (2019/00325/001) to I.L.-B.

We give a proof of the so-called Sylvester criterion for quadratic forms (for real symmetric matrices), based on elementary optimality properties of quadratic functions.

The carrot (Daucus carota L.), one of the most important vegetable crops in the world, is recognized as a source of different compounds with healthy properties. Due to their high content of anthocyanins, purple carrots have been used as a natural colorant source to face the increasing demand of consumers for non-synthetic products. However, the root developmental stage can greatly affect the phytochemical composition and, in this regard, the identification of chemical biomarkers for the optimal harvest time would be of paramount interest both from a nutritional point of view and for the agri-food industry. In the present work, the metabolic profiling of purple carrots was monitored over four months using high-resolution 1H NMR spectroscopy. Several metabolites were identified, and their quantitative variations allowed for the investigation of the carrot development processes. The metabolic profile analysis showed an increase in amino acid, NAD, and caffeic acid levels during carrot development. A more tardive harvest in December entailed an increase in levels of luteolin-7-O-glucoside, chlorogenic acid, falcarinol, and &gamma, aminobutyrate, and a decrease in carotenoids and &omega, 6 fatty acid. The results showed how the harvest time affects the composition in terms of flavonoids, phenols, and polyacetylenes, therefore, improving the bioactive compound content.

This note presents a proof of the Farkas–Minkowski theorem. Our proof does not presuppose the closedness of a finitely generated cone, nor employs separation theorems either. Even the concept of linear independence or invertibility of matrices is not necessary. Our new device consists in proving the Farkas–Minkowski theorem and the closedness of a finitely generated cone at the same time based upon mathematical induction. We make use of a minimization problem with an equality constraint, a method familiar to economics students.

We propose two di erent notations for cones generated by a set and for convex cones generated by a set, usually denoted by a same notation. We make some remarks on the Bouligand tangent cone and on the Clarke tangent cone for star-shaped sets and for locally convex sets. We give some applications of these remarks to a di erentiable optimization problem with an abstract constraint.

We extend the so-called approximate Karush---Kuhn---Tucker condition from a scalar optimization problem with equality and inequality constraints to a multiobjective optimization problem. We prove that this condition is necessary for a point to be a local weak efficient solution without any constraint qualification, and is also sufficient under convexity assumptions. We also state that an enhanced Fritz John-type condition is also necessary for local weak efficiency, and under the additional quasi-normality constraint qualification becomes an enhanced Karush---Kuhn---Tucker condition. Finally, we study some relations between these concepts and the notion of bounded approximate Karush---Kuhn---Tucker condition, which is introduced in this paper.

Aims. To make the students of Medicinal Chemistry (MC) course for doctor of pharmacy (PharmD) understand how strongly connected the chemical properties of drugs are to their clinical profiles and therapeutics, and determine students’ satisfaction degree. Design. Students in the spring 2013 section of the MC course were taught in a traditional teacher-centered manner. Students in the spring 2015 and 2016 ones had additional guided clinically relevant medicine label-based exercises. They worked in structured self-selected teams and chemically explained the clinical aspects of the selected drugs during oral communication sessions. They were given a 1 to 4 Likert-type scale satisfaction questionnaire, the data were collected and statistically treated. Results. The project was useful to show the connection between the chemical aspects of drugs and their clinical profiles (mean=3.33±0.65) and globally satisfactory (mean=3.07±0.47). The additional didactic material helped the students in the spring 2016 make the most of the MC course (mean=3.38±0.74, p=0.002). Conclusions. Medicine label-based exercises seem to be helpful to understand the connection between medicinal chemistry and pharmacotherapeutics. Feedback from students is generally quite favourable. The approach taken will continue to be modified and expanded.

In the first part of this paper we point out some basic properties of the critical cones used in second-order optimality conditions and give a simple proof of a strong second-order necessary optimality condition by assuming a “modified” first-order Abadie constraint qualification. In the second part we give some insights on second-order constraint qualifications related to second-order local approximations of the feasible set.

In this report a short and efficient synthesis of the dibenz[b,f]oxepin framework through intramolecular SNAr and McMurry reactions is described. The diaryl ethers required for the McMurry reaction have been obtained in good yields under microwave-assisted conditions of the reaction of salicylaldehydes with fluorobenzaldehydes without catalysts. Application of an intramolecular McMurry reaction to the synthesized diarylethers using TiCl4/Zn in THF gave the target dibenzo[b,f]oxepin system in 53%–55% yields.

A variety of α,β-unsaturated aldehydes and ketones gave very high-yielding Michael addition reactions with α-nitrocycloalkanones in water, at room temperature without added catalyst. These can be considered as one of the very few “on-water” Michael reactions known in the literature, because they took place in suspension or emulsion and at increased speed relative to the same transformations performed in organic solvents. A related protocol that uses very dilute, aqueous solutions of potassium carbonate as the reaction media extended the scope of the method to cyclic enones and unsaturated esters, nitriles and sulfones and is likely to take place in the bulk of the aqueous phase, i.e., “in-water”. Both preparative methods constitute environmentally benign and efficient alternatives to previously known procedures.

Some remarks are made on the use of the Abadie constraint qualification, the Guignard constraint qualifications and the Guignard regularity condition in obtaining weak and strong Kuhn-Tucker type optimality conditions in differentiable vector optimization problems.

Treatment of cyclic α-nitroketones and aromatic 1,2-dialdehydes with DBU in tetrahydrofuran containing small amounts of water proceeded through two chemodivergent one-pot domino pathways, whose outcome depended on the ring size of the starting nitroketone. Thus, α-nitrocyclohexanone underwent diastereoselective α′-arylmethylenation reactions through a nitroaldol/aldol/reverse nitroaldol mechanism. On the other hand, α-nitrocycloheptanone and α-nitrocyclooctanone afforded 2-nitroindane-1,2-diols containing three contiguous stereocenters in a highly diastereoselective fashion through a nitroaldol/retro-Dieckmann/intramolecular nitroaldol process.

This paper sums up in a common analytical structure the main results, scattered in economic literature, concerning the linearity between rate of profit and real wage in a simple Sraffa’s model. The paper is mainly based on previous results of one of the two authors and on results of Miyao (Int Econ Rev 18:151–162, 1977) and Schefold (Zeitschrift fur angewandte Mathematik und Physik 27:873–875, 1976a; Zeitschrift fur Nationalokonomie 36:21–48, 1976b).

We give a short and easy proof of the characterization of differentiable quasiconvex functions.

We take into consideration the main definitions and properties of second order local approximations of sets (or second order tangent sets or second order variational sets). We shall be mainly concerned with the “second order tangent set”, initially proposed by Kawasaki [32, 33] and extensively studied by Cominetti [15] and by Bonnans and Shapiro [8], and with the “asymptotic second order tangent cone”, initially proposed by Penot [39] and independently by Cambini, Martein and Vlach [10]. As an application we establish second order necessary and second order sufficient optimality conditions in terms of second order approximations of sets, for a vector optimization problem.

Domperidone is a prokinetic agent widely prescribed in adults and children with gastrointestinal disorders. Recently several Regulatory Agencies published safety information on the risk of long QT syndrome associated with the use of domperidone. We conducted a literature review using PubMed (1966 - Jan 2010) with the aim to locate articles on ventricular arrhytmias, Sudden Cardiac Death (SCD), long QT syndrome and Torsade de Pointes (TdP) following domperidone administration. Twenty-two papers were included in the review: three studies in vitro models, one animal study, five case reports/series, twelve clinical studies and one editorial. In vitro studies demonstrated cardiac electrophysiological effects of domperidone on the rapid component of the cardiac delayed rectifier K(+) current (I(Kr)) through the blockade of channels encoded by the Human Ether-a-go-go Related Gene (HERG). A total of fourteen cases of cardiotoxicity following intravenous (12 cases) or oral (2 cases) domperidone administration from case reports/series were identified. A case - control study, performed on a general practice observational database reported an OR: 3.8 (95% CI: 1.5-9.7) for SCD after domperidone exposure. Prescribers and other healthcare professionals should take into account the risk of QT syndrome in domperidone users and avoid administering domperidone in patients concomitantly taking strong CYP3A4 inhibitors or other QT prolonging drugs.

We take into consideration the first-order sufficient conditions, established by Jimenez and Novo (Numer. Funct. Anal. Optim. 2002; 23:303–322) for strict local Pareto minima. We give here a more operative condition for a strict local Pareto minimum of order 1.

We consider a Pareto multiobjective optimization problem with a feasible set defined by inequality and equality constraints and a set constraint, where the objective and inequality constraints are locally Lipschitz, and the equality constraints are Frechet differentiable. We study several constraint qualifications in the line of Maeda (J. Optim. Theory Appl. 80: 483�500, 1994) and, under the weakest ones, we establish strong Kuhn�Tucker necessary optimality conditions in terms of Clarke subdifferentials so that the multipliers of the objective functions are all positive.

Experimental and clinical data indicate that 3,4-methylenedioxy-N-methylamphetamine (MDMA) abuse can produce significant cardiovascular toxicity. A mechanism may be a direct toxic effect of redox active metabolites of MDMA. To evaluate the effect of a single MDMA dose on cellular antioxidant defence system and to investigate the morphology in male albino rats, total glutathione (GSH), oxidised glutathione (GSSG), ascorbic acid (AA), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and malondialdehyde (MDAL) were studied. The effects were evaluated at 3, 6, 16 and 24 h after MDMA administration. Antioxidant enzymes activity was significantly reduced: GPx (-24%) and SOD (-50%) after 3 h and GR (-19%) after 6 h from treatment. AA levels decrease (-37%) after 3 h and (-30%) after 6 h; MDAL level increased (+119%) after 3 h; GSH levels decreased after 3 (31.3%) and 6 h (37.9%) from MDMA treatment. GSSG content was not affected by ecstasy administration. Myocardial contraction band necrosis (CBN) was already visible in rats killed at 6 h. After 16 h, macrophagic monocytes around the necrotic myocardial cells were observed, and within 24 h, this infiltrate became more widespread with an early removal of the necrotic material. Calcium deposits were observed within ventricular cardiomyocytes with intact nuclei and sarcomeres. Single administration of MDMA can significantly alter the cellular antioxidant defence system and produce oxidative stress which may result in lipid peroxidation and disruption of Ca(2 +) homeostasis. The depression in Ca(2+) regulatory mechanism by reactive oxygen species ultimately results in intracellular Ca(2 +) overload, CBN and cell death.

The effects of anticancer chemotherapy on antigen-specific cytotoxic T lymphocytes (CTLs) are mostly unknown. We tested the effects of cytotoxic drugs such as 5-fluorouracil, gemcitabine, and oxaliplatin on the functional activity of antigen-specific CTL cultures derived from the peripheral blood mononuclear cells of human donors. We found that a biweekly drug-exposure of human HLA-A(*)02.01+ CTLs derived from bulk cultures led to completely different effects if occurring early (day second) or late (day thirteenth) after the in vitro stimulations with the cognate peptides. In the first case, there was a significant CTL inhibition, whereas in the second, there was a marked enhancement of the antigen-specific cytolytic activity. Results of immunocytofluorimetric studies and CTL/natural killer inhibition assays suggested that the latter effect could be related to a more selective drug-mediated inhibition of cohabitant T regulatory (reg) cells. These results were translated in an in vivo therapeutic mouse model where humanized HLA-A(*)02.01 transgenic mice inoculated with EL-4/humanized HLA-A(*)02.01 transgenic mice showed a prolonged survival and the greatest rate of cure when receiving a combined treatment with a thymidylate synthase-specific peptide vaccine and a multidrug chemotherapy regimen administered late after immunization. Tumor samples derived from this group of mice showed a reduced expression of the target thymidylate synthase antigen, a marked reduction of T(reg)s, and a noteworthy infiltration of C8+ T cells. These results may have clinical implications for the design of new translational anticancer regimens aimed at combining chemotherapy and immunotherapy.

A nonsmooth multiobjective optimization problem involving generalized Lipschitz univex functions is studied. Kuhn-Tucker type sufficient optimality conditions are obtained for a feasible solution to be an efficient or properly efficient solution. Mond-Weir type and Mond-Zhang type duality results are obtained under the aforesaid assumptions.

Background: To investigate the cardiotoxic role of reactive oxygen species (ROS) and of products derived from catecholamines auto-oxidation, we studied: (1) the response of antioxidant cardiac cellular defence systems to oxidative stress induced by norepinephrine (NE) administration, (2) the effect of NE administration on cardiac β1-adrenergic receptors by means of receptor binding assay, (3) the cellular morphological alterations related to the biologically cross-talk between the NE administration and cytokines [tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukins IL6, IL8, IL10]Methods and Results: A total of 195 male rats was used in the experiment. All animals underwent electrocardiogram (EKG) before being sacrificed. The results obtained show that NE administration influences the antioxidant cellular defence system significantly increasing glutathione peroxidase (GPx) activity, glutathione reductase (GR) and superoxide dismutase (SOD). The oxidized glutathione (GSH/GSSG) ratio significantly decreases and malondialdehyde (MDA) levels increase showing a state of lipoperoxidation of cardiac tissue. We describe a significant apoptotic process randomly sparse in the damaged myocardium and the effect of ROS on the NE-mediated TNF-α, MCP-1, and IL6, IL8, IL10 production. Conclusions: Our results support the hypothesis that catecholamines may induce oxidative damage through reactive intermediates resulting from their auto-oxidation, irrespective of their interaction with adrenergic receptors, thus representing an important factor in the pathogenesis of catecholamines-induced cardiotoxicity. The rise of the cardioinhibitory cytokines may be interpreted as the adaptive response of jeopardized myocardium with respect to the cardiac dysfunction resulting from NE injection.

Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. Previously, we have pointed out a dramatic decrease of glutathione levels in the rat brain after acetaminophen (APAP) oral administration overdose. Silymarin (SM) is a mixture of bioactive flavonolignans isolated from Silybum marianum (L.) Gaertn., employed usually in the treatment of alcoholic liver disease and as anti-hepatotoxic agent in humans. In this study, we have evaluated the effect of SM on enzymatic and non enzymatic antioxidant defensive systems in rat brain after APAP-induced damage. Male albino Wistar rats were treated with SM (200 mg/kg/die orally) for three days, or with APAP single oral administration (3 g/kg) or with SM (200 mg/kg/die orally) for 3 days and APAP single oral administration (3 g/kg) at third day. Successively the following parameters were measured: reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), enzymatic activity variations of superoxide dismutase (SOD) and malondialdehyde levels (MDA). Our results showed a significant decrease of GSH levels, AA levels and SOD activity and an increase of MDA and GSSG levels after APAP administration. After SM administration GSH and AA significantly increase and SOD activity was significantly enhanced. In the SM+APAP group, GSH values significantly increase and the others parameters remained unchanged respect to control values. These results suggest that SM may to protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels.

We give an overview on the main properties of D-stable matrices, i.e. of those square matrices $A$ for which the product DA is stable for any choice of the diagonal matrix D, with all positive diagonal elements. These matrices, introduced in economic analysis by Arrow and Mc Manus (1958), have found, besides applications in mathematical economics, applications also in other fields, such as mathematical ecology, population dynamics, the theory of electric circuits, analysis of neural networks, control theory and other questions.

Iresine herbstii Hook. (Amaranthaceae) and Brugmansia arborea (L.) Lagerheim (Solanaceae) are used in the northern Peruvian Andes for magic-therapeutical purposes. The traditional healers use Iresine herbstii with the ritual aim to expel bad spirits from the body. Furthermore, Iresine herbstii was used in association with other plants, such as Trichocereus pachanoi Britt. et Rose, for divination, to diagnose diseases, and to take possession of another identity. Also, species of Brugmansia have been reported to be used during ritual practices for magical and curative purposes. Given the above evidence, the aim of the present study is to evaluate if the central effects of Iresine herbstii and Brugmansia arborea could be associated with interaction with SNC receptors. Two Iresine herbstii extracts (methanolic and aqueous) and one Brugmansia arborea aqueous extract were tested for in vitro affinity on 5-HT(1A), 5-HT(2A), 5-HT(2C), D1, D2, alpha(1), and alpha(2) receptors by radioligand binding assays. The biological materials for binding assay (cerebral cortex) were taken from male Sprague-Dawley rats. The extracts affinity for receptors is definite as inhibition percentage of radioligand/receptor binding and measured as the radioactivity of remaining complex radioligand/receptor. The data obtained for Iresine extracts have shown a low affinity for the 5-HT(1A) receptor and no affinity for 5-HT(2A) receptor. Otherwise the methanolic extract showed affinity for 5-HT(2C) receptor (IC(50): 34.78 microg/ml) and for D1 receptor (IC(50): 19.63 microg/ml), instead the Iresine aqueous extract displayed a lower affinity for D1 (48.3% at the maximum concentration tested) and a higher value of affinity for D2 receptors (IC(50): 32.08 microg/ml). The Brugmansia aqueous extract displayed affinity for D1 receptors (IC(50): 17.68 microg/ml), D2 receptors (IC(50): 15.95 microg/ml) and weak affinity for the serotoninergic receptors. None of the three extracts showed relevant affinity to the alpha(1), and alpha(2) receptors. The results of our experiments indicate that Iresine herbstii methanolic extract was able to interact with the central 5-HT(2C) and D1 receptors and Iresine herbstii aqueous extract showed affinity for D2 receptors, thus confirming their ritual use. Instead Brugmansia arborea was able to interact only with the central dopamine receptors tested. Parallel studies are currently in progress for evaluating the extracts affinity and active components towards these and other receptor types (GABAergic).

Background: Thymidylate synthase (TS), a key enzyme in DNA synthesis, is often overexpressed in cancer cells. Some chemotherapeutic agents, such as 5-fluorouracil (5-FU), act by inhibiting TS expression. We evaluated whether a novel 28-amino acid multiepitope peptide, TS/PP, that contains the sequences of three TS-derived epitopes with binding motifs for HLA-A(*)02.01 could induce a TS-directed cytotoxic T-lymphocyte (CTL) response with antitumor activity. Methods: TS/PP peptide immunologic activity in CTL lines derived from human leukocyte antigen (HLA)-A(*)02.01 + peripheral blood mononuclear cells (PBMCs) was tested in the presence of interleukin-2 and autologous TS/PP peptide-loaded dendritic cells. Immunologic and antitumor activities of TS/PP and its toxicity were also evaluated in vivo in HLA-A(*)02.01 transgenic (HHD) mice that were vaccinated with TS/PP, control, or TS-peptide cocktail and treated with or without 5-FU chemotherapy. The mice were also inoculated subcutaneously with TS-expressing EL-4/HHD lymphoma cells to assess immune response against these tumor cells. Results: TS/PP-specific CTL lines showed a TS-multiepitopic specificity and were able to kill TS + /HLA-A(*)02.01 + breast and colon carcinoma cells. The killing ability against target cells previously exposed to sublethal doses of 5-FU was statistically significantly greater than against untreated target cells (43.5% versus 26.5% at 25/1 effector to target ratio [Difference {diff} = 17.0]; 95% confidence interval [CI] = 12.6 to 20.4) for MDA-MB-231 breast carcinoma cells and 73.5 versus 48.5 (diff = 25.0; 95% CI = 16.2 to 33.8) for the SW-1463 colon carcinoma cells. HHD mice vaccinated with TS/PP manifested a TS-peptide-specific CTL response with no sign of autoimmunity or toxicity. Furthermore, treatment of these mice with 5-FU delayed or prevented the occurrence of tumors formed by inoculation with autologous (TS + )EL-4/HHD lymphoma cells. Conclusions: The multiepitopic TS/PP vaccine induces a tumor-specific immune response in mice and is especially potent when used in combination with 5-FU-based chemotherapy.

[reaction: see text]. A unique domino reaction of alpha-nitrocycloalkanones with alpha-alkyl alpha,beta-unsaturated aldehydes in aqueous base was discovered, leading to the one-pot synthesis of hitherto unknown functionalized, bridged, bicyclic lactones containing 10-, 11-, 13-, and 15-membered rings. The structures of these heterocyclic compounds, containing also an unusual 6-hydroxy-1,2-oxazine ring, were determined by spectral and single-crystal X-ray diffraction studies.

We consider a vector optimization problem with functions defined on Banach spaces. A few sufficient optimality conditions are given and some results on duality are proved.

We consider a multiobjective optimization problem with a feasible set defined by inequality and equality constraints such that all functions are, at least, Dini differentiable (in some cases, Hadamard differentiable and sometimes, quasiconvex). Several constraint qualifications are given in such a way that generalize both the qualifications introduced by Maeda and the classical ones, when the functions are differentiable. The relationships between them are analyzed. Finally, we give several Kuhn-Tucker type necessary conditions for a point to be Pareto minimum under the weaker constraint qualifications here proposed.

1. The pharmacokinetics of mitomycin C (MMC) was evaluated during hypoxic hepatic infusion (HHMI) with arterial embolization for the treatment of unresectable liver metastases. 2. Ten patients with hepatic metastases from colorectal cancer were considered. Antiblastic infusion with MMC (20 mg/m2 at 30 ml/min) was initiated after 10 min of hepatic arterial occlusion. Peripheral venous blood samples were collected at different time intervals. MMC was assayed by high-pressure liquid chromatography (HPLC), and pharmacokinetic parameters were determined using an open, two-compartment model and linear kinetics. 3. Cmax of MMC during HHMI was 708 +/- 336.6 ng/ml, and tmax was 9.3 +/- 1.1 min. The plasma concentration-time curve showed a t1/2 alpha ranging from 1.5 to 9 min, followed by a t1/2 beta ranging from 31 to 93 min. The Cltot was 35.5 l/h/m2 with an area under the plasma concentration-time curve (AUC) ranging from 251 to 850 micrograms h/l. The same AUC parameter standardized for the amount of MMC was 15.5 mg-1. The HHMI model that we used revealed a significant increase in Cltot and a reduction in AUC when compared to the locoregional intraarterial and peripheral intravenous models (p < .001). 4. The reduction in AUC following HHMI explains the limited systemic toxicity in treated patients, with a greater total tumor exposure to the drug and improved drug activation.

Background: Hyperglycemia increases oxygen-reactive species generation and reduces the protective capabilities of antioxidant defense systems. In patients with type 1 or 2 diabetes mellitus (DM), the increased production of oxygen free radicals may be linked to the development of chronic complications of diabetes. In vitro studies have demonstrated that oral antidiabetic drugs have antioxidant effects that might be secondary to an inhibiting role in lipid peroxidation. Objective: The purpose of this study was to determine the effects of 3 common oral antidiabetic agents on oxidized anti-low-density lipoprotein antibody (o-LAb) plasma levels and on total antioxidant status (TAS). Methods: We studied in vivo patients with type 2 DM treated with long-term gliclazide, glibenclamide, or metformin therapy along with healthy control subjects. The diabetic patients were randomized to the following treatment groups: group 1, gliclazide 80 to 240 mg/d; group 2, glibenclamide 10 to 15 mg/d; and group 3, metformin 1500 mg/d. Results: Ninety-two patients with type 2 DM (group 1, 18 females, 15 males [mean age, 62.8 ± 9.5 years]; group 2, 19 females, 11 males [mean age, 63.2 ± 8.8 years]; group 3, 16 females, 13 males [mean age, 62.0 ± 5.3 years]) and 28 age- and sex-matched healthy control subjects (18 females, 10 males; mean age, 59.1 ± 5.3 years) were enrolled. In group 1, both the o-LAb level and TAS were similar to those of the control group. The o-LAb level was highest and the total antioxidant plasma level was lowest in group 3, whereas intermediate levels were found in group 2. Multivariate analysis using stepwise regression showed that the type of oral antidiabetic agent was independently associated with o-LAb and total antioxidant levels, as well as with sex, age, and type of antidiabetic agent. Conclusion: In the patients with type 2 DM in this study, gliclazide had a positive effect on the oxidation-reduction system.

We take into condideration necessary optimality conditions of minimum principle-type, that is for optimization problems having, besides the usual inequality and/or equality constraints, a set constraint. The first part pf the paper is concerned with scalar optimization problems; the second part of the paper deals with vector optimization problems.