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Results for “parameter optimization”

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PubMed2004

[Optimization of amoxicillin/clavulanate therapy based on pharmacokinetic/pharmacodynamic parameters in patients with diabetic foot infection].

AIM OF THE STUDY: Individualized optimization of amoxicillin/clavulanate (AMC) antimicrobial therapy in diabetic foot infection. METHODS: Pharmacokinetic analysis of individual steady-state plasma amoxicillin concentrations was done both in the i.v. infusion phase and in the oral phase of AMC, administered on the basis of the quantitative susceptibility of the detected microbe(s). The in vitro growth/killing dynamic parameters on model of Staphylococcus aureus as the most frequent isolate were evaluated. Therapeutic protocol optimization, leading to prediction of the earliest time to reduce the number of viable bacteria to 10-6 as a surrogate criterion of efficacy, was performed. RESULTS: Based on individual plasma amoxicillin oscillations in 17 patients suffering from infected diabetic foot ulcers and the model microbial dynamic parameters, the reduction of the number of viable bacteria was reached significantly earlier after the administration of continuous i.v. AMC infusion than after the same daily AMC dose administered intermittently. In case of highly susceptible staphylococcal strain, highly frequent oral therapy of AMC (not longer than 8 hrs dosing interval) was also sufficiently effective. Decreasing plasma amoxicillin concentrations exponentially extended the time required for effective reduction of microbes. CONCLUSION: Individualized optimization of amoxicillin/clavulanate dosage on the basis of growth/killing microbial dynamic parameters and antibiotic concentration/time fluctuations may enhance the antimicrobial effect and the treatment of infected non-critical ischemic diabetic foot ulcers.

Amoxicillin-Potassium Clavulanate Combination↗

PubMed2000

Functional assessment in the rat by ground reaction forces.

Although the rat sciatic nerve model is used extensively in the investigation of repair techniques, and a variety of evaluation methods utilized to assess the results, a means to measure directly and accurately the return of function in these animals is absent. Histologic, histomorphometric, and electrophysiologic methods can be reliable indicators of nerve regeneration but do not correlate to functional recovery. The purposes of this study were to develop apparatus to continuously measure ground reaction forces (GRF) and use GRF parameters in the assessment of gait parameters in normal rats preoperatively and following peripheral nerve severance and repair. Three neurorrhaphy methods: direct sciatic nerve repair, direct tibial nerve repair and double sciatic nerve repair simulating autograft, as well as a non-repaired tibial nerve transection were evaluated. The testing apparatus was designed to measure the spontaneous and voluntary effort of the rat with objective data. Three orthogonal components - vertical, craniocaudal (braking and propulsion), and mediolateral - of the ground reaction force were measured. Preoperative data showed that vertical forces were comparable among the four limbs but propulsion and braking forces displayed significant differences. At 12 weeks, functional recovery was most evident in the direct tibial nerve repair group and absent in the non-repaired tibial defect group. Direct sciatic nerve repairs and sciatic nerve grafts resulted in lesser degrees of improvement. Results indicated that the propulsive force is the optimal GRF parameter for evaluating recovery of useful function.

Analysis of Variance↗

PubMed2005

Angiosperm divergence times: the effect of genes, codon positions, and time constraints.

An understanding of the evolution of modern terrestrial ecosystems requires an understanding of the dynamics associated with angiosperm evolution, including the timing of their origin and diversification into their extraordinary present-day diversity. Molecular estimates of angiosperm age have varied widely, and many substantially predate the Early Cretaceous fossil appearance of the group. In this study, the effect of different genes, codon positions, and chronological constraints on node ages are examined on divergence time estimates across seed plants, with a special focus on angiosperms. Penalized likelihood was used to estimate divergence times on a phylogenetic hypothesis for seed plants derived from Bayesian analysis, with branch lengths estimated with maximum likelihood. The plastid genes atpB, psaA, psbB, and rbcL were used individually and in combination, using first and second, third, and the three codon positions, including and excluding age constraints on 20 nodes derived from a critical examination of the land-plant fossil record. The optimal level of rate smoothing according to each unconstrained and constrained dataset was obtained with penalized likelihood. Tests for a molecular clock revealed significantly unclocklike rates in all datasets. Addition of fossil constraints resulted in even greater departures from constancy. Consistently with significant deviations from a clock, estimated optimal smoothing values were low, but a strict correlation between rate heterogeneity and optimal smoothing value was not found. Age estimates for nodes across the phylogeny varied, sometimes substantially, with gene and codon position. Nevertheless, estimates based on the four concatenated genes are very similar to the mean of the four individual gene estimates. For any given node, unconstrained age estimates are more variable than constrained estimates and are frequently younger than well-substantiated fossil members of the clade. Constrained estimates of ages of clades are older than unconstrained estimates and oldest fossil representatives, sometimes substantially so. Angiosperm age estimates decreased as rate smoothing increased. Whereas the range of unconstrained angiosperm age estimates spans the fossil age of the clade, the range of constrained estimates is narrower (and older) than the earliest angiosperm fossils. Results unambiguously indicate the relevance of constraints in reducing the variability of ages derived from different partitions of the data and diminishing the effect of the smoothing parameter. Constrained optimizations of divergence times and substitution rates across the phylogeny suggest appreciably different evolutionary dynamics for angiosperms and for gymnosperms. Whereas the gymnosperm crown group originated shortly after the origin of seed plants, a long time elapsed before the origin of crown group angiosperms. Although absolute age estimates of angiosperms and angiosperm clades are older than their earliest fossils, the estimated pace of phylogenetic diversification largely agrees with the rapid appearance of angiosperm lineages in stratigraphic sequences.

Base Sequence↗

PubMed2005

[Clinical applications of transcranial magnetic stimulation for the treatment of various neurological diseases].

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in various neurological and psychiatric diseases including depression, Parkinson disease, spinocerebellar degeneration, epilepsy, urinary incontinence, movement disorders, chronic pain, migraine and chronic tinnitus, etc. Several reports showed the therapeutic effects of rTMS as a treatment of depression and Parkinson disease (PD), whereas others found no significant effects. It is by now not yet fully understood whether rTMS has a therapeutic effect on those diseases. The controversy arises from the differences of the stimulation parameters and evaluation methods of the effects in those studies. The Japanese multi-center, double blinded, sham stimulation controlled trial in 85 patients with PD showed an efficacy in both the rTMS-treated and sham stimulated patients. This result does not prove the efficacy of the rTMS in PD; on the other hand, it does not rule out the efficacy. Possible mechanism of favorable effects of rTMS is related to increasing the release of dopamine in the mesolimbic and mesostriatal system. The other Japanese multi-center, double blinded, sham stimulation controlled trial in 99 patients with spinocerebellar degeneration revealed significant therapeutic effects of rTMS in 51 patients with SCA6. We studied the effects of rTMS on seizure susceptibility in rats which prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. This finding suggests the possibility of therapeutic use of rTMS in epilepsy. Further studies should be performed aiming to reveal the optimal stimulation parameters, and are necessary to reveal the therapeutic role of the rTMS in neurological and psychiatric diseases.

Depression↗

PubMed1999

Enhanced delivery of carboplatin into brain tumours with intravenous Cereport (RMP-7): dramatic differences and insight gained from dosing parameters.

Cereport (RMP-7) is a selective bradykinin B2 receptor agonist which increases the permeability of the 'blood-brain tumour barrier' (BBTB) to increase delivery of chemotherapeutic agents to brain tumours. A series of experiments was performed in an RG2 rodent model of glioma to evaluate and refine intravenous (i.v.) parameters to optimize Cereport's clinical utility. The first experiment demonstrated that while carboplatin levels were increased by twofold when given as a bolus during the Cereport infusion, no increase in carboplatin levels were seen when Cereport and carboplatin were simultaneously co-infused for 15 min. A subsequent experiment established that a major factor responsible for the lack of an effect with the co-infusion paradigm was tachyphylaxis to Cereport during the 15 min infusion, for a progressively diminished response to Cereport occurred over that time frame, as plasma levels of carboplatin were rising. A final experiment adjusted the timing of the Cereport and carboplatin infusions so that higher plasma carboplatin levels were achieved prior to initiating the Cereport infusion. Significant uptake effects were achieved when the carboplatin infusion preceded the Cereport infusion by 10 min (i.e. 5 min overlap in the delivery of the two agents). Collectively, these data provide the first systematic evaluation of dosing parameters involving receptor-mediated changes in BBTB permeability and provide new information regarding the pharmacodynamics and potential clinical use of Cereport.

Animals↗

PubMed2005

A critical review on magnetic stimulation: what is its role in the management of pelvic floor disorders?

PURPOSE OF REVIEW: This review looks at the acute effects of magnetic stimulation on urodynamic parameters and reviews the data on its use in the management of urinary incontinence. RECENT FINDINGS: Reported cure rates for stress incontinence immediately after a course of perineal magnetic stimulation range from 12.5 to 52.9% with good improvement occurring in 32% to 41%. However the effect seems temporary and dependent on the number of sessions. Sacral and pelvic floor magnetic stimulation have also been shown to increase cystometric capacity, inhibit detrusor overactivity and resolve overactive bladder symptoms acutely. Persistence of this effect with symptomatic improvement one week after sacral magnetic stimulation has been demonstrated. How magnetic stimulation suppresses detrusor contraction is not known. Prospective trials with the Neocontrol chair (Neotonus Inc, Marietta, Georgia, USA) also showed symptomatic improvement in 71 to 87% in the short term. However, the longer term data appear mixed. SUMMARY: Overall, the data available vary too much in terms of treatment protocols, patient mix and symptom severity to determine which group of patients might benefit most and what the optimal stimulation parameters are for each condition. Mean reductions in leak parameters, although statistically significant, may not always be clinically satisfactory. The beneficial effects also appear to be temporary and continuous treatment will probably be required. Further trials are needed to determine the optimum stimulation protocols for different situations and to compare magnetic stimulation with other forms of conservative pelvic floor therapy.

Electric Stimulation Therapy↗

PubMedDate not supplied

Optimizing the diagnosis of hippocampal sclerosis using MR imaging.

PURPOSE: To establish the optimal imaging parameters and MR features of hippocampal sclerosis. METHODS: Twenty-five outpatients with intractable temporal lobe epilepsy and 10 control subjects were studied at 1.5T. Four features of hippocampal abnormality were specifically evaluated; increased hippocampal signal on T2-weighted images, decreased signal on T1-weighted images, hippocampal atrophy, and disruption of the internal hippocampal structure. RESULTS: Hippocampal sclerosis was diagnosed alone in 64% of patients and with ipsilateral pathology in a further 8%. In these 18 cases, increased hippocampal signal on T2-weighted images was seen in 77%, hippocampal atrophy in 83%, decreases signal on T1-weighted images in 83%, and disruption of the internal hippocampal structure in 89%. No abnormality was reported in any of the 10 control cases. CONCLUSIONS: Four MR features diagnostic of hippocampal sclerosis are reported. Inversion recovery images are very useful for identifying decreased signal in the hippocampus and loss of internal structure within the hippocampus. Based on an appreciation of these four features in optimized images, hippocampal sclerosis can be diagnosed with a high degree of accuracy and sensitivity.

Adolescent↗

PubMedDate not supplied

Simple electrical model of the circulation to explore design parameters for a skeletal muscle ventricle.

To efficiently investigate a variety of designs for an accessory skeletal muscle ventricle for circulatory assistance, we developed an electrical model of the human circulatory system. Heart and blood vessels were modeled as resistive-capacitive networks, pressures as voltages, blood flow as electric current, and the cardiac valves as diodes. Pumping of blood was simulated by the application of damped rectangular voltage pulses to the capacitances of the cardiac ventricles and the skeletal muscle ventricle. Three configurations of a skeletal muscle ventricle were studied: the apico-aortic, in which the skeletal muscle ventricle is interposed between the left ventricle and the abdominal aorta; the aorto-aortic, in which the skeletal muscle ventricle is interposed between the thoracic aorta and the abdominal aorta; and the atrial-aortic, in which the skeletal muscle ventricle is interposed between the left atrium and abdominal aorta. The three skeletal muscle ventricle designs were tested as counterpulsatile assist devices in simulations of the normal circulation and congestive heart failure. Performance of the various skeletal muscle ventricle designs was evaluated by comparing total output, mean left ventricular power expenditure, mean skeletal muscle ventricle power expenditure, and mean perfusion pressure of the skeletal muscle comprising the pouch. Under both normal heart and heart failure conditions, the apico-aortic design was superior to the aorto-aortic and to the atrial-aortic designs. With optimal stimulation parameters, the apico-aortic design reduced left ventricular minute work to 16% of normal during simulated heart failure while maintaining a viable resting cardiac output of 3.4 L/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Circulation↗

PubMedDate not supplied

In vitro comparative evaluations of the postantifungal effect: synergistic interaction between flucytosine and fluconazole against Candida albicans.

In vitro comparative evaluations were performed to study the efficacy of combinations of flucytosine and fluconazole in producing a postantifungal effect (PAFE) on Candida albicans. Initial studies were done to determine MIC, FIC (fractional inhibitory concentration) and optimal PAFE parameters. A turbidometric method was used to measure yeast cell growth following exposure to different concentrations of the two drugs for periods of 0.5, 1 or 2 h at temperatures of 30 degrees C and 37 degrees C. The PAFE was determined by the difference in time (h) required for growth of the control and test cultures to reach the 0.5 absorbance level following removal of the drug by dilution. Ten strains of C. albicans were then assayed (30 degrees C; 2 h exposure time) and a synergistic PAFE was evidenced with the two drugs at concentrations well below their individual MICs. PAFEs ranging from 3.8 to 10.5 h, which persisted for 1.2-2.5 h longer than those achieved with either agent separately, were evidenced when flucytosine and fluconazole were combined (flucytosine: fluconazole ratios of 1:16-1:32) at concentrations ranging from 0.024 to 0.098 micrograms ml-1 and 0.78 to 1.56 micrograms ml-1 respectively. The concentrations of each agent required to produce an optimal PAFE varied according to the C. albicans strain being assayed.

Candida albicans↗

PubMed1997

Fast and effective skin ablation with an Er:YAG laser: determination of ablation rates and thermal damage zones.

BACKGROUND AND OBJECTIVE: Er:YAG lasers are known to superficially ablate skin and other tissues with minimal thermal coagulation zones. The ablation efficacy and thus the clinical applicability of these lasers, however, was limited due to small beam diameters and repetition rates. Aim of this study was to determine the ablation efficacy and the amount of thermal damage with a new high-power high-repetition-rate Er:YAG laser and to find optimal treatment parameters for skin ablation. STUDY DESIGN/MATERIALS AND METHODS: In vitro and some in vivo ablation trials on human skin were performed with the Er:YAG laser (MCL 29, Aesculap-Meditec, Heroldsberg, Germany, 2.94 microns, max. 500 mJ per pulse, 250 microseconds pulse length, 3 or 4 mm spot size, repetition rate 7-10 Hz) and evaluated microscopically. RESULTS: The ablation threshold was around 1.6 J/cm2. The ablation rates increased linearly with the fluence, and the above-threshold ablation efficacy was around 2.5 microns per pulse per J/cm2, leading to ablation velocities of 70-100 microns per second and higher. With increasing pulse numbers applied to one tissue spot, the ablation per pulse decreased significantly. The amount of thermal damage was clearly dependent on the number of pulses applied (around 25 microns with < 10 imp., up to 100 microns with 40 imp.), whereas higher fluences increased the coagulation zones only minimally. The in vivo trials confirmed these results: overlapping pulses in the 4 J/cm2-range, applied in a sweeping motion, proved optimal for an efficient skin ablation with a smooth resulting surface and a thermal damage zone not exceeding 50 microns. CONCLUSIONS: The high power and the high repetition frequency make this laser a fast and effective tool for skin ablation without increasing the thermal damage, but the ablation remains limited to the superficial dermis, since hemostasis cannot be achieved due to the absence of coagulation.

Dermatologic Surgical Procedures↗

PubMed2006

Proteoglycan synthesis in bovine articular cartilage explants exposed to different low-frequency low-energy pulsed electromagnetic fields.

OBJECTIVE: To investigate the role of pulsed electromagnetic field (PEMF) exposure parameters (exposure length, magnetic field peak amplitude, pulse frequency) in the regulation of proteoglycan (PG) synthesis of bovine articular cartilage explants. METHODS: Bovine articular cartilage explants were exposed to a PEMF (75 Hz; 2 mT) for different time periods: 1, 4, 9, 24 h. Then, cartilage explants were exposed for 24 h to PEMFs of different magnetic field peak amplitudes (0.5, 1, 1.5, 2 mT) and different frequencies (2, 37, 75, 110 Hz). PG synthesis of control and exposed explants was determined by Na2-35SO4 incorporation. RESULTS: PEMF exposure significantly increased PG synthesis ranging from 12% at 4 h to 17% at 24 h of exposure. At all the magnetic field peak amplitude values, a significant PG synthesis increase was measured in PEMF-exposed explants compared to controls, with maximal effect at 1.5 mT. No effect of pulse frequency was observed on PG synthesis stimulation. CONCLUSIONS: The results of this study show the range of exposure length, PEMF amplitude, pulse frequency which can stimulate cartilage PG synthesis, and suggest optimal exposure parameters which may be useful for cartilage repair in in vivo experiments and clinical application.

Animals↗

PubMed1995

A Simple and Rapid Method of Transformation of Streptomyces rimosus R6 and Other Streptomycetes by Electroporation.

Usually plasmid DNA is introduced into Streptomyces strains by polyethylene glycol-mediated transformation of protoplasts. However, many Streptomyces strains are only poorly or not at all transformable via protoplasts. Therefore, we have optimized the parameters critical for the application of electrotransformation of plasmid DNA into Streptomyces species. The most critical parameters evaluated for electrotransformation of the model strain Streptomyces rimosus R6 were the pretreatment of mycelia, buffer composition, and electric field strength. The electrocompetent mycelia were prepared from 24-h-old cultures, treated mildly with lysozyme, resuspended in sucrose-glycerol-polyethylene glycol buffer, and stored in aliquots at -70 deg C. The electric field strength of 10 kV/cm at 400 (Omega) and a capacitance of 25 (mu)F was applied. The method is simple and rapid, yielding transformant colonies in 48 to 72 h. Efficiencies of 10(sup5) to 10(sup6) transformants per (mu)g of plasmid DNA were reproducibly achieved for S. rimosus R6 and its mutants, and these numbers were 10(sup2) to 10(sup3) higher than those attained by polyethylene glycol-assisted transformation of protoplasts. In addition, we show that electroporation can be applied to other Streptomyces species, such as S. lividans 66, S. coelicolor A3(2), and an S. venezuelae strain. This last one could not be transformed by the standard protoplast procedure. Our data suggest that, because of the diversity of streptomycetes, the conditions have to be optimized for each strain.

Journal Article↗

PubMed2002

A closed-loop controller for mechanical ventilation of patients with ARDS.

Mechanical ventilators are routinely used to care for patients who cannot adequately breath on their own. Management of mechanical ventilation often involves a careful watch of the patient's arterial blood-oxygen tension and requires frequent adjustment of ventilation parameters to optimize the therapy. This situation lends itself as a candidate for closed-loop control. This report describes a closed-loop control system based on well-established protocols to systematically maintain appropriate levels of positive end-expiratory pressure (PEEP) and inspired oxygen (FiO2) in patients with Adult Respiratory Distress Syndrome (ARDS). The closed-loop control system consists of an in-dwelling arterial oxygenation (PaO2) sensor (Pfizer Continucath), coupled to a Macintosh computer that continuously controls FiO2 and PEEP settings on a Hamilton Amadeus ventilator. The implemented protocols provide continuous closed-loop control of oxygenation and a balance between patient need and minimal therapy. The controller is based on a traditional proportional-integral-derivative (PID) approach. The idea is to control, or maintain, the patient's PaO2 level at a target value determined, or set, by the patient's physician. The controller also features non-linear and adaptive characteristics that allow the system to respond more aggressively to "threatening" levels of PaO2. Another benefit of the control system is the ability to display, monitor, record and store all system parameters, settings, and control variables for future analysis and study. The system was extensively tested in the laboratory and in animal trials prior to use on human subjects. The results of a small clinical trial indicated that the system maintained control of the patient's therapy nearly 84% of the time. During the remainder of this time, the controller was interrupted primarily for suctioning, PaO2 sensor calibration or replacement. The response of the closed-loop controller was found to be appropriate, reliable and safe in patients with ARDS.

Algorithms↗

PubMed2006

Fabrication and characterization of six electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for tissue engineering applications.

The most common synthetic biodegradable polymers being investigated for tissue engineering applications are FDA approved, clinically used poly(alpha-hydroxy esters). To better assess the applicability of the electrospinning technology for scaffold fabrication, six commonly used poly(alpha-hydroxy esters) were used to prepare electrospun fibrous scaffolds, and their physical and biological properties were also characterized. Our results suggest that specific, optimized fabrication parameters are required for each polymer to produce scaffolds that consist of uniform structures morphologically similar to native extracellular matrix. Scanning electron microscopy (SEM) revealed a highly porous, three-dimensional structure for all scaffolds, with average fiber diameter ranging from 300nm to 1.5microm, depending on the polymer type used. The poly(glycolic acid) (PGA) and poly(d,l-lactic-co-glycolic acid 50:50) (PLGA5050) fibrous structures were mechanically stiffest, whereas the poly(l-lactic acid) (PLLA) and poly(epsilon-caprolactone) (PCL) scaffolds were most compliant. Upon incubation in physiological solution, severe structural destruction due to polymer degradation was found in the PGA, poly(d,l-lactic acid) (PDLLA), PLGA5050, and poly(d,l-lactic-co-glycolic acid 85:15) (PLGA8515) fibrous scaffolds, whereas PLLA and PCL fibrous scaffolds maintained a robust scaffold structure during the same time period, based on macroscopic and SEM observations. In addition, PLLA scaffolds supported the highest rate of proliferation of seeded cells (chondrocytes and mesenchymal stem cells) than other polymeric scaffolds. Our findings showed that PLLA and PCL based fibrous scaffolds exhibited the most optimal structural integrity and supported desirable cellular response in culture, suggesting that such scaffolds may be promising candidate biomaterials for tissue engineering applications.

Animals↗

PubMed2006

Optimization of a sampling system for recovery and detection of airborne porcine reproductive and respiratory syndrome virus and swine influenza virus.

The objective of this research was to optimize sampling parameters for increased recovery and detection of airborne porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV). Collection media containing antifoams, activated carbons, protectants, and ethylene glycol were evaluated for direct effects on factors impacting the detection of PRRSV and SIV, including virus infectivity, viability of continuous cell lines used for the isolation of these viruses, and performance of reverse transcriptase PCR assays. The results showed that specific compounds influenced the likelihood of detecting PRRSV and SIV in collection medium. A subsequent study evaluated the effects of collection medium, impinger model, and sampling time on the recovery of aerosolized PRRSV using a method for making direct comparisons of up to six treatments simultaneously. The results demonstrated that various components in air-sampling systems, including collection medium, impinger model, and sampling time, independently influenced the recovery and detection of PRRSV and/or SIV. Interestingly, it was demonstrated that a 20% solution of ethylene glycol collected the greatest quantity of aerosolized PRRSV, which suggests the possibility of sampling at temperatures below freezing. Based on the results of these experiments, it is recommended that air-sampling systems be optimized for the target pathogen(s) and that recovery/detection results should be interpreted in the context of the actual performance of the system.

Air Microbiology↗

PubMed2006

Effect of substituents on activation parameters in aliphatic S(N)2 reactions. A DFT study.

The activation parameters and optimized structures of the reactants and transition states in the S(N)2 reactions of substituted pyridines and N,N-dimethylanilines with methyl iodide were computed at the DFT level in different solvents. The measured and calculated deltaG/deltaH/deltaS versus sigma plots proved to be linear, and their slopes, the deltadeltaG, deltadeltaH, and deltadeltaS reaction constants, were determined. The least solvent-dependent deltadeltaG reaction constants can be computed with acceptable accuracy. The calculated deltadeltaS data decrease only very slightly with the jointly increasing electron-withdrawing effect of the substituents and tightness of the transition states. The measured deltadeltaS values are influenced mainly by the change of solvation in the reactions, and deltadeltaH is also influenced by the reorganization of the solvent. Consequently, the experimental and calculated deltadeltaS and deltadeltaH reaction constants may deviate considerably from each other. In dipolar aprotic solvents the measured deltadeltaS was less than zero, and in protic solvents it was greater than zero. The ordering of the solvent molecules around the transition state with increasing charge is increased in the former but decreased in the latter media, as compared to the bulk of the solvents. The calculated deltaG(o), deltaH(o), and deltaS(o) parameters of the unsubstituted compounds agree relatively well with the experimental data for reactions of neutral molecules in dipolar aprotic solvents (e.g., XC6H4N(CH3)2 + CH3I). On the other hand, the measured and calculated activation parameters may show considerable deviations for reactions of ions (e.g., XC5H4NCH3+ + I-) and for any reaction in protic solvents.

Journal Article↗

PubMed2006

[Process of human platelets loaded with rehalose before lyophilization].

The aim of this research was to study the technology and methods of loading lyoprotectant-trehalose into cytoplasm of human platelets before lyophilization, to optimize experimental conditions of loading trehalose, to investigate the changes of platelets response to agonists and activation after incubation of platelets for 4 hours at 37 degrees C in the presence of lyoprotectant-trehalose, to protract the figures of loading efficiency and intracellular trehalose concentration versus incubation time, temperature and external trehalose concentration, to optimize loading parameters. The response of platelets to different agonists--thrombin, ADP, collagen and ristocetin were measured respectively by APACT2 aggregometer before and after loading trehalose into platelets; the expressions of CD62p and PAC-1 on platelet membranes in the presence and absence of reversible platelets activation inhibitors were measured by flow cytometry respectively before and after loading trehalose into cytoplasm of platelets. The results showed that the loading efficiency was linear to incubation time (2 hours later) and incubation temperature (rang from 30 degrees C to 40 degrees C), respectively. The loading efficiency almost reached 60% when the platelets were incubated at 37 degrees C for 4 hours. The intracellular trehalose concentration was higher with the increase of the extracellular trehalose concentration (< 50 mmol/L). Compared to untreated groups, the values of MPV and aggregation to different agonists in treated groups showed no significant difference, respectively (P > 0.01). After incubation of platelets for 4 hours, the expression of CD62p increased to some extent, however, the expression of CD62p decreased again when the reversible platelets activation inhibitor PGE-1 and adenosine were added to the incubation buffer. It is concluded that 37 degrees C, 4 hours and the extracellular trehalose concentration < 50 mmol/L are the optimal conditions for loading with trehalose. The processing of loading with trehalose before platelet lyophilization has no significant effects on response of platelets to agonists and activation.

Blood Platelets↗

PubMed2005

Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains. A theoretical study.

For the past two decades much research on selective photothermolysis of port wine stain vasculature has been devoted to optimizing laser parameters. Unfortunately, 60% of patients still respond suboptimally to laser therapy, despite significant innovations in treatment strategies and laser technology. Here we present a novel treatment approach based on combining selective photothermolysis with the administration of prothrombotic and/or anti-fibrinolytic pharmaceutical agents, with the aim of enhancing vaso-occlusion and post-treatment remodelling in difficult-to-target vessels. A hypercoagulable state of blood will instill laser-induced occlusive thrombosis in a wider array of vessel diameters at greater dermal depths, whereby larger vascular segments will ultimately undergo the chronic inflammatory processes that result in blood volume reduction, and thus lesional blanching. With thrombosis as a primary trigger for these inflammatory processes, we have extrapolated the threshold damage profile that is required for clinically relevant thrombus formation. Consequently, a recently proposed model of thrombus organization, in which recanalization is associated with endothelial progenitor cell-mediated neovasculogenesis, is elaborated in the framework of lesional blanching and juxtaposed to angiogenic reconstruction of affected dermal vasculature. Since neovasculogenesis and angiogenesis are regulated by the degree of vaso-occlusion and corollary drop in local oxygen tension, both can be manipulated by the administration of procoagulant pharmaceuticals. Lastly, in an effort to optimally balance selective photothermolysis with pharmacokinetics and clinical safety, the use of a gold nanoshell drug delivery system, in which the procoagulant drugs are encapsulated by a wavelength-modulated, gold-coated polymer matrix, is proposed. We have termed this modality site-specific pharmaco-laser therapy.

Adjuvants, Pharmaceutic↗

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