Biomedical subjects

Qizhi Zhang

Publications and source records attributed to Qizhi Zhang.

12 recordsLinked to original sources

PubMed2006

Quantitative reconstruction of refractive index distribution and imaging of glucose concentration by using diffusing light.

We show that a two-step reconstruction method can be adapted to improve the quantitative accuracy of the refractive index reconstruction in phase-contrast diffuse optical tomography (PCDOT). We also describe the possibility of imaging tissue glucose concentration with PCDOT. In this two-step method, we first use our existing finite-element reconstruction algorithm to recover the position and shape of a target. We then use the position and size of the target as a priori information to reconstruct a single value of the refractive index within the target and background regions using a region reconstruction method. Due to the extremely low contrast available in the refractive index reconstruction, we incorporate a data normalization scheme into the two-step reconstruction to combat the associated low signal-to-noise ratio. Through a series of phantom experiments we find that this two-step reconstruction method can considerably improve the quantitative accuracy of the refractive index reconstruction. The results show that the relative error of the reconstructed refractive index is reduced from 20% to within 1.5%. We also demonstrate the possibility of PCDOT for recovering glucose concentration using these phantom experiments.

Algorithms↗

PubMed2006

Two-dimensional bioluminescence tomography: numerical simulations and phantom experiments.

The reconstruction of internal light sources in bioluminescence tomography (BLT) is a challenging inverse problem because of the limited amount of information available compared with that for other kinds of tomography such as fluorescence tomography in which external illumination sources are used. We demonstrated previously, using phantom experiments, that a target containing luciferases could be detected tomographically when the target was located relatively close to the imaging boundary. Here we describe an improved BLT reconstruction method that can detect luciferase-containing targets located anywhere within an imaging domain. The method is tested with numerical simulations and further confirmed with several phantom experiments.

Algorithms↗

PubMed2006

Finite-element-based photoacoustic tomography: phantom and chicken bone experiments.

We describe a photoacoustic image reconstruction algorithm that is based on the finite-element solution to the photoacoustic wave equation in the frequency domain. Our reconstruction approach is an iterative Newton method coupled with combined Marquardt and Tikhonov regularizations that can extract the spatial distribution of optical-absorption property in heterogeneous media. We demonstrate this algorithm by using phantom and chicken bone measurements from a circular scanning photoacoustic tomography system. The results obtained show that millimeter-sized phantom objects and chicken bones and/or joints can be clearly detected using our finite-element-based photoacoustic tomography method.

Algorithms↗

PubMed2006

Lectin-conjugated PEG-PLA nanoparticles: preparation and brain delivery after intranasal administration.

In order to improve the absorption of nanoparticles in the brain following nasal administration, a novel protocol to conjugate biorecognitive ligands-lectins to the surface of poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles was established in the study. Wheat germ agglutinin (WGA), specifically binding to N-acetyl-D-glucosamine and sialic acid, both of which were abundantly observed in the nasal cavity, was selected as a model lectin. The WGA-conjugated nanoparticles were prepared by incorporating maleimide in the PLA-PEG molecular and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothialane thiolated WGA. Coupling of WGA with the PEG-PLA nanoparticles was confirmed by the existence of gold-labeled WGA-NP under TEM. The retention of biorecognitive activity of WGA after the covalent coupling procedure was confirmed by haemagglutination test. The resulting nanoparticles presented negligible nasal ciliatoxicity and the brain uptake of a fluorescent marker-coumarin carried by WGA functionized nanoparticles was about 2 folds in different brain tissues compared with that of coumarin incorporated in the unmodified ones. Thus, the technique offered a novel effective noninvasive system for brain drug delivery, especially for brain protein and gene delivery.

Administration, Intranasal↗

PubMed2005

Pharmacokinetic behavior in plasma, cerebrospinal fluid and cerebral cortex after intranasal administration of hydrochloride meptazinol.

The aim of this paper is to investigate the pharmacokinetic behavior of hydrochloride meptazinol (MEP) in plasma, cerebrospinal fluid (CSF) and cerebral cortex after intranasal administration (8 mg/kg) in male Sprague-Dawley rats. The pharmacokinetic study of intravenous administration (8 mg/kg) was also performed in rats. CSF and cerebral cortex samples were collected by serial CSF sampling and intracerebral microdialysis, respectively. The concentration of MEP in the biological samples was measured by high performance liquid chromatography (HPLC). It was determined that the absorption of MEP from the nasal cavity to systemic circulation was rapid and complete. The concentration-time profile showed a prolonged duration of MEP concentration in CSF and cortex following intranasal administration. The ratios of AUC values of intranasal to intravenous administrations were 0.96, 1.07 and 1.81 in plasma, CSF and cortex dialysate, respectively. In conclusion, intranasal administration of MEP is a promising alternative to traditional administration modes. Olfactory mucosa did not present intranasal MEP another pathway, in addition to systemic absorption, for transport to the brain.

Administration, Intranasal↗

PubMed2004

A novel method to calculate the extent and amount of drug transported into CSF after intranasal administration.

The aim of this paper is to establish a novel method to calculate the extent and amount of drug transported to brain after administration. The cerebrospinal fluid (CSF) was chosen as the target region. The intranasal administration of meptazinol hydrochloride (MEP) was chosen as the model administration and intravenous administration was selected as reference. According to formula transform, the extent was measured by the equation of X(A)CSF, infinity/X0 = Cl(CSF) AUC(0-->infinity)CSF/X0 and the drug amount was calculated by multiplying the dose with the extent. The drug clearance in CSF (Cl(CSF)) was calculated by a method, in which a certain volume of MEP solution was injected directly into rat cistern magna and then clearance was assessed as the reciprocal of the zeroth moment of a CSF level-time curve normalized for dose. In order to testify the accurateness of the method, 14C-sucrose was chosen as reference because of its impermeable characteristic across blood-brain barrier (BBB). It was found out that the MEP concentrations in plasma and CSF after intranasal administration did not show significant difference with those after intravenous administration. However, the extent and amount of MEP transported to CSF was significantly lower compared with those to plasma after these two administrations. In conclusion, the method can be applied to measure the extent and amount of drug transported to CSF, which would be useful to evaluate brain-targeting drug delivery.

Administration, Intranasal↗

PubMed2004

Liquid chromatographic method for the determination of rizatriptan in human plasma.

A high-performance liquid chromatographic (HPLC) method with fluorescence detection has been developed for the determination of rizatriptan in human plasma. Following a single-step liquid-liquid extraction with methyl tertiarybutyl ether, the analytes were separated using a mobile phase consisting of 0.05% (v/v) triethylamine in water (adjusting to pH 2.75 with 85% phosphoric acid) and acetonitrile (92:8, v/v). Fluorescence detection was performed at an excitation wavelength of 225nm and an emission wavelength of 360nm. The linearity for rizatriptan was within the concentration range of 0.5-50ng/ml. The intra- and inter-day precisions of the method were not more than 8.0%. The lower limit of quantification (LLOQ) was 0.5ng/ml for rizatriptan. The method was sensitive, simple and repeatable enough to be used in pharmacokinetic studies.

Calibration↗

PubMed2004

Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain.

The purpose of this study was to improve the solubility and enhance the brain uptake of nimodipine (NM) in an o/w microemulsion, which was suitable for intranasal delivery. Three microemulsion systems stabilized by the nonionic surfactants either Cremophor RH 40 or Labrasol, and containing a variety of oils, namely isopropyl myristate, Labrafil M 1944CS and Maisine 35-1 were developed and characterized. The nasal absorption of NM from microemulsion formulation was investigated in rats. The optimal microemulsion formulation consisted of 8% Labrafil M 1944CS, 30% Cremophor RH 40/ethanol (3:1) and water, with a maximum solubility of NM up to 6.4 mg/ml, droplet size of 30.3 +/- 5.3 nm, and no ciliotoxicity. After a single intranasal administration of this preparation at a dose of 2 mg/kg, the plasma concentration peaked at 1 h and the absolute bioavailability was about 32%. The uptake of NM in the olfactory bulb from the nasal route was three folds, compared with intravenous (i.v.) injection. The ratios of AUC in brain tissues and cerebrospinal fluid to that in plasma obtained after nasal administration were significantly higher than those after i.v. administration. These results suggest that the microemulsion system is a promising approach for intranasal delivery of NM for the treatment and prevention of neurodegenerative diseases.

Absorption↗

PubMed2004

Differentiation of cysts from solid tumors in the breast with diffuse optical tomography.

RATIONALE AND OBJECTIVES: Near-infrared diffuse optical tomography (DOT) is an emerging imaging technology that has the potential to offer enhanced contrast resolution over the existing technologies for detection and diagnosis of breast cancer. Thus far, the clinical evaluation of DOT has been largely limited to solid tumors. A pilot clinical study focused on DOT imaging of breasts with cysts is presented. MATERIALS AND METHODS: Six cases were studied using the recently developed compact, parallel-detection DOT system. Images characterizing the tissue absorption and scattering were obtained with a finite element-based reconstruction algorithm. The optical images were compared with the mammograms and sonograms. In one case, in vitro measurements of optical properties were conducted for the fluid obtained from needle aspiration. RESULTS: Substantial contrast between cyst and adjacent parenchyma is observed. For the six cases evaluated, the locations and sizes of cysts imaged optically are accurate and consistent with the mammographic and sonographic findings. For the case that aspiration was performed, the absorption and scattering coefficients imaged in the cyst region are quantitatively accurate compared with that measured in vitro from the fluid aspirated. CONCLUSION: This pilot study shows that cysts ranging from 1-4 cm in diameter can be quantitatively imaged. They can be differentiated from solid breast tumors because cysts generally demonstrate lower absorption and scattering coefficients compared with the surrounding normal tissue, whereas solid tumors show concurrent higher absorption and scattering related to the normal tissue.

Adult↗

PubMed2003

Mechanism of enhanced cardiac function in mice with hypertrophy induced by overexpressed Akt.

Transgenic mice with cardiac-specific overexpression of active Akt (TG) not only exhibit hypertrophy but also show enhanced left ventricular (LV) function. In 3-4-month-old TG, heart/body weight was increased by 60% and LV ejection fraction was elevated (84 +/- 2%, p < 0.01) compared with nontransgenic littermates (wild type (WT)) (73 +/- 1%). An increase in isolated ventricular myocyte contractile function (% contraction) in TG compared with WT (6.1 +/- 0.2 versus 3.5 +/- 0.2%, p < 0.01) was associated with increased Fura-2 Ca2+ transients (396 +/- 50 versus 250 +/- 24 nmol/liter, p < 0.05). The rate of relaxation (+dL/dt) was also enhanced in TG (214 +/- 15 versus 98 +/- 18 microm/s, p < 0.01). L-type Ca2+ current (ICa) density was increased in TG compared with WT (-9.0 +/- 0.3 versus 7.2 +/- 0.3 pA/pF, p < 0.01). Sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) protein levels were increased (p < 0.05) by 6.6-fold in TG, which could be recapitulated in vitro by adenovirus-mediated overexpression of Akt in cultured adult ventricular myocytes. Conversely, inhibiting SERCA with either ryanodine or thapsigargin affected myocyte contraction and relaxation and Ca2+ channel kinetics more in TG than in WT. Thus, myocytes from mice with overexpressed Akt demonstrated enhanced contractility and relaxation, Fura-2 Ca2+ transients, and Ca2+ channel currents. Furthermore, increased protein expression of SERCA2a plays an important role in mediating enhanced LV function by Akt. Up-regulation of SERCA2a expression and enhanced LV myocyte contraction and relaxation in Akt-induced hypertrophy is opposite to the down-regulation of SERCA2a and reduced contractile function observed in many other forms of LV hypertrophy.

Adenoviridae↗

PubMed2003

Neurally-mediated increase in calcineurin activity regulates cardiac contractile function in absence of hypertrophy.

OBJECTIVE: The calcineurin pathway has been involved in the development of cardiac hypertrophy, yet it remains unknown whether calcineurin activity can be regulated in myocardium independently from hypertrophy and cardiac load. METHODS: To test that hypothesis, we measured calcineurin activity in a rat model of infrarenal aortic constriction (IR), which affects neurohormonal pathways without increasing cardiac afterload. RESULTS: In this model, there was no change in arterial pressure over the 4-week experimental period, and the left ventricle/body weight ratio did not increase. At 2 weeks after IR, calcineurin activity was increased 1.8-fold (P<0.05) and remained elevated at 4 weeks (1.7-fold, P<0.05). Similarly, the cardiac activity of calcium calmodulin kinase II (CaMKII) was increased significantly after IR, which confirms a regulation of Ca(2+)-dependent enzymes in this model. In cardiac myocytes, the increased activity of calcineurin was accompanied by a significant decrease in L-type Ca(2+) channel activity (I(Ca)) and contraction velocity (-dL/dt). Cardiac denervation prevented the activation of calcineurin after IR, which demonstrates that a neurohormonal mechanism is responsible for the changes in enzymatic activity. In addition, cardiac denervation suppressed the effects of IR on I(Ca) and -dL/dt, which shows that calcineurin activation is related to altered contractility. However, action potential duration, the densities of inward rectifier K(+) currents (I(K1)), and outward K(+) currents (I(to) and I(K)) were not altered in IR myocytes. CONCLUSIONS: Calcineurin can be activated in the heart through a neural stimulus, which induces alterations in Ca(2+) currents and contractility. These effects occur in the absence of myocyte hypertrophy, electrophysiological changes in action potential, and K(+) channel currents.

Animals↗

PubMed2003

Determination of the active metabolite of sibutramine by liquid chromatography-electrospray ionization tandem mass spectrometry.

A sensitive and specific method for the determination of the active primary amine metabolite of sibutramine, N-di-desmethylsibutramine (BTS 54,505), in human plasma was developed, based on high-performance liquid chromatography (HPLC)-electrospray ionization tandem mass spectrometry (MS-MS). The samples were extracted from plasma with methyl tert.-butyl ether, followed by separation and evaporation after addition of the internal standard, propranolol, and basification with sodium hydroxide. The residue was reconstituted in mobile phase and injected into the HPLC-MS-MS system. Chromatography was performed on an ODS MS column with a mobile phase consisting of acetonitrile (containing 0.1% trifluoroacetic acid, v/v)-0.1% trifluoroacetic acid (55:45, v/v) at a flow-rate of 0.3 ml/min. Multiple reaction monitoring using precursor-->product ion combinations at m/z 252.00-->125.00 and 260.00-->115.70 was applied to determine BTS 54,505 and propranolol, respectively. Linearity was confirmed in the concentration range 0.328-32.8 ng/ml in human plasma and the imprecision of this assay was less than 19.90% over the entire concentration range. The method is sufficiently sensitive and repeatable to be used in pharmacokinetic studies.

Appetite Depressants↗