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Radiation-induced brain injury (RIBI) is a significant challenge in radiotherapy for head and neck tumors, impacting patients' quality of life. In exploring potential treatments, this study focuses on memantine hydrochloride and hydrogen-rich water, hypothesized to mitigate RIBI through inhibiting the NLRP3/NLRC4/Caspase-1 pathway. In a controlled study involving 40 Sprague-Dawley rats, divided into five groups including a control and various treatment groups, we assessed the effects of these treatments on RIBI. Post-irradiation, all irradiated groups displayed symptoms like weight loss and salivation, with notable variations among different treatment approaches. Particularly, hydrogen-rich water showed a promising reduction in these symptoms. Histopathological analysis indicated substantial hippocampal damage in the radiation-only group, while the groups receiving memantine and/or hydrogen-rich water exhibited significant mitigation of such damage. Molecular studies, revealed a decrease in oxidative stress markers and an attenuated inflammatory response in the treatment groups. Immunohistochemistry further confirmed these molecular changes, suggesting the effectiveness of these agents. Echoing recent scientific inquiries into the protective roles of specific compounds against radiation-induced damages, our study adds to the growing body of evidence on the potential of memantine and hydrogen-rich water as novel therapeutic strategies for RIBI.

Background: Memantine, an NMDA antagonist, has shown to be an effective and well-tolerated pharmacological therapy for the reduction of cognitive decline in the general population with Alzheimer's disease. Individuals with Down syndrome (trisomy 21) have higher rates of cognitive decline than the general population in addition to a greatly increased risk for the development of early-onset Alzheimer's disease. The potential efficacy of Memantine as a therapy for cognitive improvement in DS patients is not well understood. Objective: To assess the effectiveness of Memantine in comparison to placebo as a pharmacological therapy for patients with Down syndrome. Search strategy: Multiple databases including Pubmed, CENTRAL, CDSR, and clinicaltrials.gov were searched with terms including “Memantine Hydrochloride” and “Trisomy 21.” Selection criteria: Randomized, double-blind, placebo-controlled trials measuring tolerability, efficacy, and safety of memantine in DS patients were used. Three (3) studies were ultimately included. Data collection and analysis: Standard Mean Difference (SMD), Odds Ratio (OR) and 95 % confidence intervals (CIs) were calculated to assess the significance of intervention. Main results: No statistically significant therapeutic effect was found upon administration of Memantine relative to placebo in DS patients.

The present work deals with the development and validation of an UV-Vis spectrophotometric method for the quantitative determination of Memantine hydrochloride. To execute this task, Memantine (MMT), being an UV inactive molecule, was first derivatized by conducting conventional diazotization reaction and further coupling with N,N-dimethyl aniline (DMA) at 2 to 5°C. The newly formed MMT-DMA complex showed characteristic absorbance maximum at 354 nm. The spectroscopic estimation was achieved by scanning the spectrum between 200 and 800 nm on Shimadzu UV-1900 spectrophotometer. The developed method was validated further with respect to linearity, accuracy, precision, LOD, LOQ and robustness. The method showed expediency over the previously reported methods including instantaneous reaction, facile synthesis and high sensitivity. Moreover, the method has proven to be successful when applied for quantitative determination of marketed pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Radiation-induced brain injury (RIBI) is a significant challenge in radiotherapy for head and neck tumors, impacting patients' quality of life. In exploring potential treatments, this study focuses on memantine hydrochloride and hydrogen-rich water, hypothesized to mitigate RIBI through inhibiting the NLRP3/NLRC4/Caspase-1 pathway. In a controlled study involving 40 Sprague-Dawley rats, divided into five groups including a control and various treatment groups, we assessed the effects of these treatments on RIBI. Post-irradiation, all irradiated groups displayed symptoms like weight loss and salivation, with notable variations among different treatment approaches. Particularly, hydrogen-rich water showed a promising reduction in these symptoms. Histopathological analysis indicated substantial hippocampal damage in the radiation-only group, while the groups receiving memantine and/or hydrogen-rich water exhibited significant mitigation of such damage. Molecular studies, revealed a decrease in oxidative stress markers and an attenuated inflammatory response in the treatment groups. Immunohistochemistry further confirmed these molecular changes, suggesting the effectiveness of these agents. Echoing recent scientific inquiries into the protective roles of specific compounds against radiation-induced damages, our study adds to the growing body of evidence on the potential of memantine and hydrogen-rich water as novel therapeutic strategies for RIBI. [Display omitted] • Memantine and HRW Mitigate RIBI via NLRP3/NLRC4/Casp1 Pathway: Initial Evaluation. • Memantine and HRW groups showed histopathological improvements compared to IR group. • Molecular evidence: Reduced oxidative stress & pyroptosis in memantine & HRW groups. • Immunohistochemistry validates molecular findings, affirming treatment. • Study supports memantine and HRW as novel RIBI treatments. [ABSTRACT FROM AUTHOR]

Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Current drugs can only relieve symptoms, but cannot really cure AD. Cerebralcare Granule® (CG) is a Traditional Chinese medicine (TCM) containing a variety of biologically active compounds. In our previous studies, CG has shown a beneficial effect against memory impairment in mice caused by d-galactose. However, whether CG can be used as a complementary medicine for the treatment of AD remains unexplored. Here, we use a combination of CG and memantine hydrochloride (Mm) to treat Alzheimer-like pathology and investigate the effects and mechanisms in vivo. Methods The histology of brain was examined with Hematoxylin–eosin (HE) staining, Golgi staining and Thioflavin S staining. ELISA was applied to assess the expression levels or activities of CAT, SOD, GSH-Px, MDA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) in serum, as well as the levels of IL-6, IL-1β, and TNF-α in the mice brain. Western blotting was used to assess the expression of β-secretase (BACE1), amyloid precursor protein (APP), APPβ, APPα, synaptophysin (SYN), growth-associated protein 43 (GAP43), and postsynaptic density 95 (PSD95). Results In the present study, the combination group (CG + Mm) significantly attenuated Alzheimer-like behavior without adverse effects in APP/PS1 mice, indicating its high degree of safety and efficacy after long-term treatment. CG + Mm reduced AD pathological biomarker Aβ plaque accumulation by inhibiting BACE1 and APP expression (P

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Current drugs can only relieve symptoms, but cannot really cure AD. Cerebralcare Granule® (CG) is a Traditional Chinese medicine (TCM) containing a variety of biologically active compounds. In our previous studies, CG has shown a beneficial effect against memory impairment in mice caused by d-galactose. However, whether CG can be used as a complementary medicine for the treatment of AD remains unexplored. Here, we use a combination of CG and memantine hydrochloride (Mm) to treat Alzheimer-like pathology and investigate the effects and mechanisms in vivo. Methods: The histology of brain was examined with Hematoxylin–eosin (HE) staining, Golgi staining and Thioflavin S staining. ELISA was applied to assess the expression levels or activities of CAT, SOD, GSH-Px, MDA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) in serum, as well as the levels of IL-6, IL-1β, and TNF-α in the mice brain. Western blotting was used to assess the expression of β-secretase (BACE1), amyloid precursor protein (APP), APPβ, APPα, synaptophysin (SYN), growth-associated protein 43 (GAP43), and postsynaptic density 95 (PSD95). Results: In the present study, the combination group (CG + Mm) significantly attenuated Alzheimer-like behavior without adverse effects in APP/PS1 mice, indicating its high degree of safety and efficacy after long-term treatment. CG + Mm reduced AD pathological biomarker Aβ plaque accumulation by inhibiting BACE1 and APP expression (P < 0.05 or P < 0.001). Besides, the combination group markedly inhibited the levels of IL-1β, IL-6, and TNF-α in hippocampus (P < 0.001), as well as activities of SOD, CAT, and GSH-Px in serum (P < 0.001). By contrast, the combination group improved synaptic plasticity by enhancing SYN, PSD95, and GAP43 expression. Conclusions: Taken together, these data supported the notion that CG combined with Mm might ameliorate the cognitive impairment through multiple pathways, suggesting that CG could play a role as complementary medicine to increase anti-AD effect of chemical drugs by reducing Aβ deposition, neuroinflammation, oxidative damage, and improving synaptic plasticity. [ABSTRACT FROM AUTHOR]

Objective. To assess the efficacy of memantine hydrochloride in correcting gait disturbances in patients with Parkinson's disease (PD). Materials and methods. The study group consisted of 30 patients with PD in whom standard antiparkinsonism therapy was supplemented with memantine hydrochloride (Akatinol Memantine) at dose of 20 mg/day for three months; the reference group consisted of 25 PD patients who received only antiparkinsonism therapy. Both groups of patients were investigated using clinical scales to detect cognitive deficit and with a computerized protocol for assessment of gait parameters; subjects were investigated twice with an interval of three months. Results. During treatment with memantine, patients of the study group showed an increase in the total score on the Mini Mental State Examination (MMSE), while digital gait analysis demonstrated improvements in the ratio of stride phases and an increase in gait rhythm as compared with the group of patients not receiving memantine. Conclusions. Thus, the gait improvements obtained in this study confirm that correction of cortical gait disturbances in PD patients using memantine hydrochloride is a potential therapeutic approach. [ABSTRACT FROM AUTHOR]

A method for quantitative determination of memantine hydrochloride by HPLC with mass spectrometric detection (HPLC-MS), suitable for the study of dissolution profiles of tablets "Mematon IС" was developed. Chromatographic determination was performed using a mobile phase of methanol - 0.1% (v/v) aqueous solution of formic acid (55:45) on a column of Zorbax Eclipse Plus C18 size 10 cm × 4.6 mm (3.5 μm) at a flow rate of 1 ml/min. The linearity interval in the appropriate dissolution media is 35 - 150 % of the normalized content of memantine hydrochloride in the tablet. The method is validated on the parameters of specificity, accuracy, correctness, linearity in the studied range of concentrations, robustness. The stability of the tested solutions and reference solutions in the case of their storage at room temperature for 24 hours was confirmed. It is established that in the case of the study of solutions prepared in a dissolution medium of 0.1 M hydrochloric acid solution pH 1.2, there is a need to preneutralize hydrochloric acid before analysis, because it, as stronger than formic acid, almost completely ionizes all dissolved molecules, which leads to a significant deviation of the linear dependence of the analytical signal on the concentration of the analyte. Neutralization is performed with 0.1 M sodium hydroxide solution, which is added to the sample of the test solution. The release of more than 85 % of memantine hydrochloride in 15 min in all dissolution media indicates the similarity of the dissolution profiles and does not require the calculation of the similarity factor f2. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of memantine hydrochloride combined with ginkgo biloba extract on the serum brain-derived neurotrophic factor (BDNF), neurotrophic factor (NGF) concentration, dopamine (DA) levels and cognitive function of alzheimer's disease patients. Methods: A total of 92 patients with alzheimer's disease admitted to our hospital from June 2017 to July 2018 were randomly divided into 49 patients in the control group and 43 patients in the research group. The control group was treated with memantine hydrochloride, and the research group was treated with ginkgo biloba extract on the basis of the control group. The clinical efficacy, changes of serum BDNF, NGF, DA levels, cognitive function, MMSE, ADL scores before and after treatment and incidence of adverse reactions were compared between the two groups. Results: After treatment, the total effective rate of research group was 90.70%, which was significantly higher than that of the control group (69.39%, P<0.05). Before treatment, there was no significant difference in the serum levels of BDNF, NGF, DA, MMSE and ADL between the two groups (P>0.05). After treatment, the indexes in both groups were significantly higher than those before treatment, which were significantly higher in the research group than those in the control group (P<0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P>0.05). Conclusion: Memantine hydrochloride combined with ginkgo biloba extract can improve the efficacy and the cognitive function of Alzheimer's disease patients, which may be related to the increased serum levels of BDNF, NGF and DA. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of memantine hydrochloride on improving neurocognitive function in patients with ischemic stroke. Methods Patients with hemorrhagic stroke who were treated in the officer consultation department of General Hospital of PLA from June to December 2016 were retrospectively studied. According to whether or not they were taking memantine, the patients were divided into the memantine group and the control group. The data including age, sex, BMI, follow-up time, the neurocognitive function score were collected. The neurocognitive function score was assessed by the Montreal Cognitive Assessment Scale (MoCA). Results There was no significant difference in age, BMI, and follow-up time between the two groups. The MoCA score was(19.19±3.23) in memantine group, (18.47±3.03) in control group, P=0.651;(21.06±2.62)in memantine group,(19.19±2.87) in control group,P=0.038 at 2 weeks;(23.50±2.00) in memantine group,(21.30±2.16) in control group,P=0.002 at 4 weeks;At the last follow-up, memantine group was(24.69±2.09), control group was (23.22±2.08), P=0.031. Conclusion Memantine could effectively improve neurocognitive function in patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

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Traumatic brain injury (TBI) often leads to substantial adverse cognitive and health outcomes, including permanent disability and death. Preventing these outcomes requires attenuation of the secondary biochemical damage that follows the initial biomechanical insult, but a clinically proven pharmacotherapeutic capable of such has not been identified. In fact, the heterogeneous nature of TBI and the complexity of secondary injury cascades suggest a polytherapeutic approach that targets multiple pathways might be necessary. We and others have reported that 17β-estradiol (E2) is neuroprotective in models of central nervous system injury. Although E2 is neuroprotective and favorably modulates several key components of secondary injury, it does not effectively block the destructive excitotoxic cascade. Thus, administering E2 in combination with a second drug that targets excitotoxicity, such as the FDA-approved uncompetitive NMDA receptor antagonist memantine hydrochloride, may provide additional benefits. Here, we assessed the neuroprotective potential of an acutely administered intravenous bolus dose of a combination of memantine and E2 after induction of experimental TBI in the clinically relevant lateral fluid percussion model. Our results indicate that the combination of these drugs conferred neuroprotection by increasing neuronal survival and decreasing neuronal degeneration in the hippocampus and cortex ipsilateral to injury. Furthermore, administration of this combination improved vestibulomotor deficits and modestly reduced anxiety. We conclude that further investigation of the neuroprotective potential of memantine administered with E2 is warranted. [ABSTRACT FROM AUTHOR]

In this work, we focus on measuring solubility and analyzing solution thermodynamics of Memantine hydrochloride in different binary solvent mixtures (ethanol + acetonitrile); (ethanol + water); and (ethanol + ethyl acetate) at the temperature range of 278.15–333.15 K under atmospheric pressure. The solubility data was correlated by the modified Apelblat model, the general cosolvency model and the Jouyban-Acree + van't Hoff model. The result show that modified Apelblat equation is best because of the lowest MD data and ethyl acetate could be used as effective anti-solvent in the crystallization process of Memantine hydrochloride In addition, the thermodynamic properties of the solution process, including the Gibbs free energy, enthalpy, and entropy were calculated by the van't Hoff analysis. [ABSTRACT FROM AUTHOR]

Free-radical-mediated processes are involved in a variety of physiological events, while oxidative stress and related redox deregulation are implicated in various pathological events. Tripeptide glutathione plays an important role in the antioxidant defense of the brain, particularly in the maintenance of the optimal redox state in neurons and glial cells. We studied the combined effects of pantothenic acid derivatives, pantothenol and calcium pantothenate, and memantine, which is a glutamate receptor antagonist that is widely used for the treatment of dementia, on amnesia induced by scopolamine in rats. Scopolamine induced amnesia in rats; however, unexpectedly, this effect was even more expressed in the memantine-pretreated animals. Memory impairments were less manifested in the rats that were pretreated with memantine in combination with panthenol or calcium pantothenate. The detrimental scopolamine effect on memory was accompanied by significant depletions of glutathione and coenzyme A in the brain. While memantine recovered the glutathione status to some extent, it nevertheless further aggravated the scopolamine influence on coenzyme A levels. An alleviation of scopolamine-induced memory impairments that was observed after combined pretreatment with memantine and panthenol or calcium pantothenate was accompanied by a normalization of coenzyme A levels, while the effects on glutathione redox did not correlate with the behavioral data. [ABSTRACT FROM AUTHOR]

A simple and sensitive method for simultaneous derivatization and hollow fiber liquid phase microextraction (HF-LPME) followed by high performance liquid chromatography–fluorescence detection (HPLC–FL) to determine memantine hydrochloride (MT) in human plasma was developed. The derivatization and microextraction was combined to a single step to ensure the precision. What is more, the derivatization reaction accelerated the mass transfer during the process of microextraction. The hollow fiber was filled with cyclohexane and dansyl chloride (derivatization agent) as acceptor phase and submersed in the alkalinized plasma sample. The system was submitted to stirring at 800 rpm for 50 min at 40 °C. Different experimental parameters were systematically evaluated by response surface methodology. Under the optimized conditions, the calibration curve was linear in the range of 1–100 ng/mL ( r = 0.9991) with a limit of detection of 0.1 ng/mL ( S/N = 3). The precision estimated as the relative standard deviation (RSD) was less than 4.5% and the accuracy was 94.3–100.7%. The present method was successfully applied to determine MT in human plasma samples. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the bioequivalence of memantine hydrochloride test and reference preparations in healthy volunteers . Methods: Twenty-four healthy male volunteers were randomly administered with an oral single dose of 10 mg test or reference memantine hydrochloride tablets in an open-label，2-period crossover study with a 28 d washout period . The blood samples were collected at the scheduled time before and after administration . The plasma concentrations of memantine were de­termined by LC-MS/MS method . The pharmacokinetic parameters tmax，cmax，AUCch，AUC0-ra，MRT and t1/2 were calculated by non compartmental model method .Results：The main pharmacokinetic parameters of the test and reference memantine hydro - chloride preparations were as follows : tmax (8 .29 ± 4 .7) and (9 .04 ± 4.2) h ; cmax (13 .3 ± 1 .82) and (12.1 ± 1.66) ng /ml; AUC0-∞（1140±200) and (1080±224) ng·h· ml-1 ;t1/2 (60 .2± 11.4) and (59.1 ± 12.6) h, respectively . The relative bioavail­ability of the test preparations was (107.1 ± 12 .6 )%. Ninety percent confidence intervals (CI) of both the geometric mean value ratios of AUCc-t and cmax were 80%-125%. Conclusion: Memantine hydrochloride test and reference preparations have bioequivalence. [ABSTRACT FROM AUTHOR]

Memantine hydrochloride pellets is prepared with starch pellets of 80~90g as the core pellets, microcrystalline cellulose (MCC) of 120g as filler, which are mixed with memantine hydrochloride of 30g, and hydroxypropyl methyl cellulose (HPMC) of 3% (mass fraction) and 3 X 10-3 Pa • s(viscosity) as binder. The quality of the prepared pellets is evaluated. The yield of the pellets is over 80%, the particle size is uniform, and the roundness, liquidity and drug content meet the requirements. The memantine hydrochloride pellets could be prepared by centrifugal granulator. The prescription and the operation parameters are determined. The drug content could be determined by non-aqueous titration. [ABSTRACT FROM AUTHOR]

A 49-year-old healthy man developed sudden unconsciousness under inadequate ventilation. Blood gas analysis showed carboxyhemoglobin of 7.3%. After normobaric oxygen therapy, he recovered completely 7 days later. At 3 weeks after carbon monoxide (CO) exposures, memory and gait disturbances appeared. Neurological examination revealed Mini-Mental State Examination (MMSE) score of 5 of 30 points, leg hyper-reflexia with Babinski signs, and Parkinsonism. Brain fluid-attenuated inversion recovery imaging disclosed symmetric hypointense lesions in the thalamus and the globus pallidus, and hyperintense lesions in the cerebral white matter. Brain single-photon emission tomography (SPECT) scanning with 99mTechnesium-ethyl cysteinate dimer displayed marked hypoperfusion in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. He was diagnosed as CO poisoning and treated with hyperbaric oxygen therapy. The neurological deficits were not ameliorated. At 9 weeks after neurological onset, methylprednisolone (1000 mg/day, intravenous, 3 days) and memantine hydrochloride (20 mg/day, per os) were administered. Three days later, MMSE score was increased from 3 to 20 points. Neurological examination was normal 3 weeks later. Brain SPECT exhibited 20% increase of regional cerebral blood flows in the cerebellum, the thalamus, the basal ganglia, and the entire cerebral cortex. These clinicoradiological changes supported that the treatment with steroid pulse and memantine hydrochloride could prompt recovery from neurological dysfunction and cerebral hypoperfusion. Further clinical trials are warranted whether such combined therapy can attenuate neurological deficits and cerebral hypoperfusion in patients with CO poisoning. [Copyright &y& Elsevier]

Memantine hydrochloride is one of the first novel class medications for treatment of Alzheimer's disease. In this work, a biomimetic potentiometric sensor, based on a non-covalent imprinted polymer, was fabricated for the recognition and determination of memantine in pure drug and tablet pharmaceutical form. The molecularly imprinted polymer was synthesized by precipitation polymerization, using memantine hydrochloride as a template molecule, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linking agent. The sensor was developed by dispersing the memantine imprinted polymer particles in dibutyl sebacate plasticizer and embedding in poly(vinyl chloride) matrix. The wide linear range (10−5−10−1 M), with a near Nernstian response of 57.4 mV/decade, a limit of detection 6.0 × 10−6 M, fast response time (~15 s) and a satisfactory long-term stability (4 months) are characterizations of the proposed sensor. The sensor showed a high selectivity and a sensitive response to the template in aqueous system. The standard electrode potentials were determined at different temperatures and used to calculate the isothermal coefficient of the electrode. It was used as indicator electrode in potentiometric determination of memantine in pharmaceutical formulations. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Activation of NMDA receptors by glutamate is particularly important in the initial stages of memory consolidation. Memantine, a noncompetitive NMDA receptor antagonist, ameliorates memory impairment under certain circumstances, despite blocking the activation of NMDA receptors. The present experiments tested the hypothesis that memantine can improve memory deficits induced by isolation stress in day-old chicks (Gallus gallus domesticus) trained in a one-trial taste-avoidance task. Three experiments assessed the effects of memantine at different concentrations and in combination with isolation stress. The results of Experiment 1 indicate that, under normal, non-stressed conditions, memory in control animals is strong and 15.0mM memantine impairs memory, similar to that seen in many studies of the effects of NMDA receptor antagonists on learning. However, the results of Experiments 2 and 3 showed that, when chicks were exposed to isolation stress during the pre-training period, memory formation for saline-injected control animals was impaired and 5.0mM memantine significantly improved memory in an inverted U-shaped dose response function. The current results extend the findings that memantine can ameliorate memory impairment and supports the hypothesis that memantine, despite its action to reduce NMDA receptor activity, can facilitate normalized memory acquisition. [Copyright &y& Elsevier]

This present paper deals with the development and validation of a stability indicating high performance liquid chromatographic method for the quantitative determination of Memantine hydrochloride. Memantine hydrochloride was derivatized with 0.015 M 9-fluorenylmethyl chloroformate (FMOC) and 0.5 M borate buffer solution by keeping it at room temperature for about 20 minutes and the chromatographic separation achieved by injecting 10 μL of the derivatized mixture into a Waters HPLC system with photodiode array detector using a kromasil C18 column (150 x 4.6 mm), 5 μ. The mobile phase consisting of 80% acetonitrile and 20% phosphate buffer solution and a flow rate of 2 milliliter/minute. The Memantine was eluted at approximately 7.5 minutes. The volume of FMOC used in derivatization, concentration of FMOC and derivatization time was optimized and used. Forced degradation studies were performed on bulk sample of Memantine hydrochloride using acid (5.0 Normal (N) hydrochloric acid), base (1.0 N sodium hydroxide), oxidation (30% hydrogen peroxide), thermal (105°C), photolytic and humidity conditions. The developed LC method was validated with respect to specificity, precision (% RSD about 0.70%), linearity (linearity of range about 70-130 μg/mL), ruggedness (Overall % RSD about 0.35%), stability in analytical solution (Cumulative % RSD about 0.11% after 1450 min.) and robustness. [ABSTRACT FROM AUTHOR]