The effect of modafinil on the rat dopamine transporter and dopamine receptors D1–D3 paralleling cognitive enhancement in the radial arm maze

A series of drugs have been reported to increase memory performance modulating the dopaminergic system and herein modafinil was tested for its working memory (WM) enhancing properties. Reuptake inhibition of dopamine, serotonin (SERT) and norepinephrine (NET) by modafinil was tested. Sixty male Sprague–Dawley rats were divided into six groups (modafinil-treated 1–5–10 mg/kg body weight, trained and untrained and vehicle treated trained and untrained rats; daily injected intraperitoneally for a period of 10 days) and tested in a radial arm maze (RAM), a paradigm for testing spatial WM. Hippocampi were taken 6 h following the last day of training and complexes containing the unphosphorylated or phosphorylated dopamine transporter (DAT-CC and pDAT-CC) and complexes containing the D1–3 dopamine receptor subunits (D1–D3-CC) were determined. Modafinil was binding to the DAT but insignificantly to SERT or NET and dopamine reuptake was blocked specifically (IC50 = 11.11 μM; SERT 1547 μM; NET 182 μM). From day 8 (day 9 for 1 mg/kg body weight) modafinil was decreasing WM errors (WMEs) in the RAM significantly and remarkably at all doses tested as compared to the vehicle controls. WMEs were linked to the D2R-CC and the pDAT-CC. pDAT and D1–D3-CC levels were modulated significantly and modafinil was shown to enhance spatial WM in the rat in a well-documented paradigm at all the three doses and dopamine reuptake inhibition with subsequent modulation of D1–3-CC is proposed as a possible mechanism of action. © 2015 Karabacak, Sase, Aher, Sase, Saroja, Cicvaric, Höger, Berger, Bakulev, Sitte, Leban, Monje and Lubec

Simultaneous Estimation and Validation of Multicomponent Formulation in Tablets by Spectrophotometric Method

Two methods for the simultaneous estimation of atorvastatin calcium, glimepiride and metformin hydrochloride in three-component solid dosage forms have been developed. First method involved solving simultaneous equations based on measurement of absorbance at three wavelengths, 247.2 nm, 224.8 nm and 236 nm as the λmax of atorvastatin calcium, glimepiride and metformin hydrochloride respectively while in the second method the instrument is preprogrammed to collect and compile the spectral data from the scan of standards and produces the result by matrix calculations. The linearity for three drugs was in the range of 5-30 μg/ml. The procedures were successfully applied for the simultaneous determination of three drugs in laboratory prepared mixtures and commercial tablet preparation. High recovery and low % COV revealed the reliability of the methods indicating proposed methods are accurate and precise for the simultaneous estimation of three drugs in pure and tablet formulation. Keywords: Atorvastatin calcium, Glimepiride, Metformin hydrochloride, Simultaneous equation method. Multiwavelength Spectroscop

Development and Validation of UV-Spectrophotometric Method for Estimation of Metformin Hydrochloride and Pioglitazone in Tablet Dosage Form

Simple, sensitive, rapid and accurate UV spectroscopic methods have been developed for the estimation of metformin hydrochloride and pioglitazone in tablet dosage forms. Simultaneous estimation and dual-wavelength methods were developed and validated using solvent methanol. Both drugs show linearity at 5-40 µg/ml for both methods. The suggested techniques have been effectively implemented in pharmaceutical formulations to the evaluation of quoted drugs. Recovery research was conducted to verify the method's accuracy, precision. The techniques have been validated under ICH guidelines. Keywords: Metformin hydrochloride, Pioglitazone, Simultaneous estimation method and Dual wavelength method

Filmless versus film-based systems in radiographic examination costs: an activity-based costing method

Background: Since the shift from a radiographic film-based system to that of a filmless system, the change in radiographic examination costs and costs structure have been undetermined. The activity-based costing (ABC) method measures the cost and performance of activities, resources, and cost objects. The purpose of this study is to identify the cost structure of a radiographic examination comparing a filmless system to that of a film-based system using the ABC method. Methods: We calculated the costs of radiographic examinations for both a filmless and a film-based system, and assessed the costs or cost components by simulating radiographic examinations in a health clinic. The cost objects of the radiographic examinations included lumbar (six views), knee (three views), wrist (two views), and other. Indirect costs were allocated to cost objects using the ABC method. Results: The costs of a radiographic examination using a filmless system are as follows: lumbar 2,085 yen; knee 1,599 yen; wrist 1,165 yen; and other 1,641 yen. The costs for a film-based system are: lumbar 3,407 yen; knee 2,257 yen; wrist 1,602 yen; and other 2,521 yen. The primary activities were "calling patient," "explanation of scan," " take photographs," and "aftercare" for both filmless and film-based systems. The cost of these activities cost represented 36.0% of the total cost for a filmless system and 23.6% of a film-based system. Conclusions: The costs of radiographic examinations using a filmless system and a film-based system were calculated using the ABC method. Our results provide clear evidence that the filmless system is more effective than the film-based system in providing greater value services directly to patients

Greenhouse production systems for people

Environmentally sound greenhouse production requires that: demand for market products is understood; greenhouse design addresses the climate circum-stances; input resources are available and consumed efficiently, and; there must be a reasonable balance of production products to the environmental impacts from system. Engineering greenhouse production systems to meet these requirements must include: a cost-effective and structurally sound facility; various sub-systems controlled to interact harmoniously together; and educated and experienced system operators. The major components of the environmentally sound greenhouse are: Super-structure and glazing (for a specific location and climate conditions); Climate control sub-systems (ventilation, heating, cooling, CO2 control, pest protection, energy conservation, shading/lighting); Monitoring and control (for system operations data; decision-support systems; and, operations control procedures); Automation systems (for quality control, and effective resource utilization); and Crop nutrient delivery system (for control of plant root zone environment). Effective greenhouse engineering design, operations and management, must incorporate input from academic, private and public sectors of society. Therefore this team of researchers, educators, industry/ business, and experienced crop production operators has cooperated to include a current real-world applications perspective to the presentation. Greenhouse produc¬tion systems are described that not only include the fundamentals for success, but also the combination of sub-systems, at appropriate technological levels to meet the design requirements and restrictions for success. The collaborators on this presentation have capabilities and experiences of successful greenhouse production systems from around the world that range from simple, low-input systems to highly complex production systems. Our goal is to emphasize the current basics of greenhouse design, and to support the symposium about greenhouse production systems for people

Report of the Lancet Commission on the Value of Death: bringing death back into life

The story of dying in the 21st century is a story of paradox. While many people are overtreated in hospitals with families and communities relegated to the margins, still more remain undertreated, dying of preventable conditions and without access to basic pain relief. The unbalanced and contradictory picture of death and dying is the basis for this Commission

Pollen and Phytoliths from Fired Ancient Potsherds as Potential Indicators for Deciphering Past Vegetation and Climate in Turpan, Xinjiang, NW China

It is demonstrated that palynomorphs can occur in fired ancient potsherds when the firing temperature was under 350°C. Pollen and phytoliths recovered from incompletely fired and fully fired potsherds (ca. 2700 yrs BP) from the Yanghai Tombs, Turpan, Xinjiang, NW China can be used as potential indicators for reconstructing past vegetation and corresponding climate in the area. The results show a higher rate of recovery of pollen and phytoliths from incompletely fired potsherds than from fully fired ones. Charred phytoliths recovered from both fully fired and incompletely fired potsherds prove that degree and condition of firing result in a permanent change in phytolith color. The palynological data, together with previous data of macrobotanical remains from the Yanghai Tombs, suggest that temperate vegetation and arid climatic conditions dominated in the area ca. 2700 yrs BP

Direct Observation of the Myosin Va Recovery Stroke That Contributes to Unidirectional Stepping along Actin

Myosins are ATP-driven linear molecular motors that work as cellular force generators, transporters, and force sensors. These functions are driven by large-scale nucleotide-dependent conformational changes, termed “strokes”; the “power stroke” is the force-generating swinging of the myosin light chain–binding “neck” domain relative to the motor domain “head” while bound to actin; the “recovery stroke” is the necessary initial motion that primes, or “cocks,” myosin while detached from actin. Myosin Va is a processive dimer that steps unidirectionally along actin following a “hand over hand” mechanism in which the trailing head detaches and steps forward ∼72 nm. Despite large rotational Brownian motion of the detached head about a free joint adjoining the two necks, unidirectional stepping is achieved, in part by the power stroke of the attached head that moves the joint forward. However, the power stroke alone cannot fully account for preferential forward site binding since the orientation and angle stability of the detached head, which is determined by the properties of the recovery stroke, dictate actin binding site accessibility. Here, we directly observe the recovery stroke dynamics and fluctuations of myosin Va using a novel, transient caged ATP-controlling system that maintains constant ATP levels through stepwise UV-pulse sequences of varying intensity. We immobilized the neck of monomeric myosin Va on a surface and observed real time motions of bead(s) attached site-specifically to the head. ATP induces a transient swing of the neck to the post-recovery stroke conformation, where it remains for ∼40 s, until ATP hydrolysis products are released. Angle distributions indicate that the post-recovery stroke conformation is stabilized by ≥5 kBT of energy. The high kinetic and energetic stability of the post-recovery stroke conformation favors preferential binding of the detached head to a forward site 72 nm away. Thus, the recovery stroke contributes to unidirectional stepping of myosin Va

Scopolamine Administration Modulates Muscarinic, Nicotinic and NMDA Receptor Systems

Studies on the effect of scopolamine on memory are abundant but so far only regulation of the muscarinic receptor (M1) has been reported. We hypothesized that levels of other cholinergic brain receptors as the nicotinic receptors and the N-methyl-D-aspartate (NMDA) receptor, known to be involved in memory formation, would be modified by scopolamine administration