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Biomedical subjects

Massoud Motamedi

Publications and source records attributed to Massoud Motamedi.

At least 19 recordsLinked to original sources

Whole-body hyperthermia induces up-regulation of vascular endothelial growth factor accompanied by neovascularization in cardiac tissue.

Whole-body hyperthermia (WBH) promotes cardiac protection against ischemia/reperfusion injury, in part by up-regulation of heat shock proteins (HSP). Whether heat stress also promotes up-regulation of angiogenic factors or induces endothelial cell proliferation is unknown. We studied the effects of heat stress on up-regulation of vascular endothelial growth factor (VEGF) and growth of new blood vessels following WBH. Anesthetized rats were subjected to WBH at 42 degrees C for 15 min. The control (n=23) and heated (n=55) groups were allowed to recover for 4, 12, 24, 48, or 72 h prior to harvesting the heart for Western Blot and immunohistochemical assessment of VEGF, HSP70, and platelet endothelial cell adhesion molecular-1 (PECAM-1). A significant increase in VEGF and HSP70 expression was observed as early as 4 h post-heating. The Western Blot analysis revealed a close temporal correlation between up-regulation of HSP70 and VEGF. Maximum VEGF and HSP70 expression occurred at 12 and 24 h post-heating in the left and right ventricles, respectively. The right ventricle showed the greatest expression of both VEGF and HSP70. Immunostaining revealed that VEGF was focally increased in the endothelial cells of capillaries, small arteries, and in interstitium. At 48 and 72 h post-heating, multiple areas of extensive capillary proliferation occurred in the epicardial region of the right ventricle. These observations were verified by quantitative analysis of the density of blood vessels as determined by PECAM-1 staining. Our experiments show that sublethal heat stress can lead to upregulation of both VEGF and HSP70 in cardiac tissue and promote focal endothelial proliferation in the heart.

Animals↗

Temporary dermal scatter reduction: quantitative assessment and implications for improved laser tattoo removal.

BACKGROUND AND OBJECTIVES: Temporary dermal clearing, i.e., reduction in the attenuation coefficient of the dermis and epidermis, may lead to improved laser tattoo removal by providing increased efficiency of laser delivery to embedded ink particles and enabling the use of shorter wavelength visible lasers more effective on certain inks. STUDY DESIGNS/MATERIALS AND METHODS: In a hairless guinea pig model of human tattoo, we tested both intradermal and transdermal application of glycerol, using visual inspection, spectral analysis, and optical coherence tomography techniques to assess effectiveness. In controlled experiments, we compared the outcomes of single laser treatment sessions for both cleared and uncleared tattoo sites using Q-switched 755 and 532 nm lasers on three different inks. RESULTS: Intradermal injection of clearing agents induced dermal clearing but resulted in necrosis and scar. Transdermal application of clearing agents resulted in moderate reversible clearing, which was localized to the superficial layers of the skin and did not result in complications. Statistically significant differences in laser treatment outcome were observed relative to a number of treatment parameters including the treatment of certain tattoos by short wavelength lasers. CONCLUSIONS: Temporary clearing of superficial skin layers may be performed in an apparently safe and reliable manner. Clearing should lead to increased penetration of laser light to tattoos and should, therefore, increase treatment efficiency. Further study is needed to determine the degree to which this change is of clinical value.

Animals↗

Optoacoustic, noninvasive, real-time, continuous monitoring of cerebral blood oxygenation: an in vivo study in sheep.

BACKGROUND: Current, invasive cerebral oxygenation monitors require either retrograde jugular venous bulb cannulation or intraparenchymal probe insertion. There is no accurate, noninvasive, continuous monitor of cerebral blood oxygenation. METHODS: The authors designed, built, and tested novel optoacoustic instrumentation that continuously measures blood oxygenation in the superior sagittal sinus (SSS) in vivo in 12 anesthetized sheep. In this technique, laser pulses generate acoustic signals, the amplitudes and slopes of which are proportional to oxyhemoglobin saturation in the SSS. Optoacoustic signals from the SSS measured through the scalp and cranium were compared with directly measured oxyhemoglobin saturation in blood withdrawn from the cannulated SSS. RESULTS: In the first experiments (feasibility), FIO2 changes produced rapid corresponding changes in optoacoustic signals and arterial oxygen saturation. In the second experiments (validation), the authors correlated oxyhemoglobin saturation in the SSS with optoacoustic signals and developed quantifying algorithms. In eight of nine validation experiments, the authors quantified optoacoustic signals by subtracting the temporal profile at low FIO2 (0.08-0.1) from profiles at higher FIO2 and integrating those signals in the range from 3 to 5 micros. In each validation experiment, optoacoustic signals showed tight temporal association and good linear correlation with measured oxyhemoglobin saturation (r2 0.75 to 0.99 for eight individual experiments). CONCLUSIONS: The optoacoustic system detects signals induced in the SSS and optoacoustic signals from the SSS linearly correlate with oxyhemoglobin saturation. The data suggest that the optoacoustic technique merits clinical evaluation.

Acoustic Stimulation↗

Inverted colloidal crystals as three-dimensional cell scaffolds.

A new type of three-dimensional scaffold with inverted colloidal crystal geometry for the investigation of topological effects in cell cultures is introduced in this publication. The scaffolds are made by infiltration of the hexagonal crystal lattice of polystyrene spheres with sol-gel formulation and subsequent annealing. It possesses a relatively high degree of order among existing cell scaffolds and affords tight control over the scaffold porosity and tissue organization. The prepared scaffolds can be a convenient system for the investigation of cell-cell and cell-matrix interactions. Their biocompatibility is demonstrated for human hepatocellular carcinoma HEP G2 and human bone marrow HS-5 cell cultures. A preliminary effect of the scaffold topology on cell proliferation is observed. HEP G2 hepatocytes form a large number of 10-15 cell colonies on scaffolds made from 75-microm spheres, while their number diminishes for scaffolds from 10- and 160-microm spheres. Under similar conditions, HS-5 forms smaller colonies consisting of three to four cells in 90-microm cavities.

Bone Marrow Cells↗

Unique temperature-activated neurons from pit viper thermosensors.

Rattlesnakes, copperheads, and other pit vipers have highly sensitive heat detectors known as pit organs, which are used to sense and strike at prey. However, it is not currently known how temperature change triggers cellular and molecular events that activate neurons supplying the pit organ. We dissociated and cultured neurons from the trigeminal ganglia (TG) innervating the pit organs of the Western Diamondback rattlesnake (Crotalus atrox) and the copperhead (Agkistrodon contortix) to investigate electrophysiological responses to thermal stimuli. Whole cell voltage-clamp recordings indicated that 75% of the TG neurons from C. atrox and 74% of the TG neurons from A. contortix showed a unique temperature-activated inward current (IDeltaT). We also found an IDeltaT-like current in 15% of TG neurons from the common garter snake, a species that does not have a specialized heat-sensing organ. A steep rise in the current-temperature relationship of IDeltaT started just below 18 degrees C, and cooling temperature-responsive TG neurons from 20 degrees C resulted in an outward current, suggesting that IDeltaT is on at relatively low temperatures. Ion substitution and Ca2+ imaging experiments indicated that IDeltaT is primarily a monovalent cation current. IDeltaT was not sensitive to capsaicin or amiloride, suggesting that the current did not show similar pharmacology to other mammalian heat-sensitive membrane proteins. Our findings indicate that a novel temperature-sensitive conductance with unique ion permeability and low-temperature threshold is expressed in TG neurons and may be involved in highly sensitive heat detection in snakes.

Action Potentials↗

Phase-sensitive optical low-coherence reflectometry for the detection of analyte concentrations.

Optical techniques may potentially be used for noninvasive glucose sensing. We investigated the application of phase-sensitive optical low-coherence reflectometry (PS-OLCR) to the measurement of analyte concentrations. The dependence of the PS-OLCR signal on the concentration of various analytes, including aqueous solutions of glucose, calcium chloride, magnesium chloride, sodium chloride, potassium chloride, potassium bicarbonate, urea, bovine serum albumin, and bovine globulin, were determined in clear and turbid media. Obtained results demonstrated (1) a high degree of sensitivity and accuracy of the phase measurements of analyte concentrations with PS-OLCR; (2) a concentration-dependent change in the phase-shift for glucose that is significantly greater than that of other analytes sampled over the same physiological range; and (3) a high submillimolar sensitivity of PS-OLCR for the measurement of glucose concentration. Further exploration of the application of PS-OLCR to the noninvasive, sensitive, and specific monitoring of glucose concentration seems warranted.

Biosensing Techniques↗

Simvastatin-induced myocardial protection against ischemia-reperfusion injury is mediated by activation of ATP-sensitive K+ channels.

OBJECTIVES: Previous studies have suggested that the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors attenuate ischemia-reperfusion injury. We investigated whether pretreatment with simvastatin reduces myocardial infarct size and whether glyburide, a non-selective inhibitor of the ATP-sensitive K channels, abrogates this infarct size-limiting effect. METHODS: Sprague-Dawley rats were treated with either simvastatin (20 mg/kg per day) or saline alone for 3 days. Additional groups of rats were treated as above and on the fourth day they received intravenous glyburide (0.3 mg/kg). All rats underwent 30 min of coronary artery occlusion followed by 180 min of reperfusion. Ischemic myocardium at risk was assessed with blue dye and infarct size with triphenyltetrazolium chloride. RESULTS: Infarct size, expressed as a percentage of the myocardium at risk, was significantly smaller in the simvastatin group (n = 8, 20.8 +/- 3.4%) than in the placebo group (n = 6, 40.1 +/- 2.7%) (P = 0.001). Glyburide abolished the protective effect of simvastatin with infarct size being 34.2 +/- 6.9% and 29.7 +/- 3.9% of the area at risk in the simvastatin group (n = 7) and placebo (n = 7) group, respectively (P = 0.58). CONCLUSIONS: Simvastatin significantly reduced myocardial infarct size. The protective effect was completely abrogated by glyburide, strongly suggesting that this protective effect is mediated via activation of the ATP-sensitive K channels.

ATP-Binding Cassette Transporters↗

Monitoring of rabbit cornea response to dehydration stress by optical coherence tomography.

PURPOSE: To evaluate the application of optical coherence tomography (OCT) for continuous noninvasive monitoring and quantification of the dynamics of corneal response after exposure of the cornea to dehydrating stress. METHODS: The changes in central corneal thickness (CCT) and scattering properties of the cornea were monitored with OCT in rabbit cornea in vivo after topical application of a glycerin-based hypertonic agent (HA) or prolonged surface evaporation of the cornea. The observed changes in backscatter were correlated with the changes in corneal hydration. RESULTS: An inverse relationship was found between the logarithm of the intensity of backscatter within the cornea and the degree of corneal hydration at which the intensity of the backscatter changed up to 20 times between the peak of the de- and rehydration phases. An analytical relationship is derived between the magnitude of the backscatter from the stroma and the extent of corneal hydration. Furthermore, depending on the concentration of the drug, a peak overshoot in corneal thickness in the range of 40% to 90% was detected during the rehydration process after topical application of the HA. At a 100% concentration of HA, the average dehydration rate was 74 microm/min, whereas the average rehydration rate was 12.4 microm/min. The same parameters for surface evaporation were 2.7 and 1.5 microm/min, respectively. CONCLUSIONS: OCT may offer a unique capability to quantitatively monitor the dynamics of corneal response and to assess corneal function based on noninvasive detection of the changes in the optical properties and morphology of the cornea after topical application of dehydrating agents.

Animals↗

The use of the hairless guinea pig in tattoo research.

The study and optimization of tattoo removal continues to be of importance in the dermatology community. Robust animal models whose skin is physiologically similar to humans and who are easily handled are desirable. To this end, we report on our experience with the hairless guinea pig as a model for tattoo research. This research was conducted as part of a larger study toward increased efficacy of laser tattoo removal. Here we report on procedures for both placement and aftercare of tattoos which result in superior tattoo quality and retention.

Aftercare↗

Precision of measurement of tissue optical properties with optical coherence tomography.

Accurate and noninvasive measurement of tissue optical properties can be used for biomedical diagnostics and monitoring of tissue analytes. Noninvasive measurement of tissue optical properties (total attenuation and scattering coefficients, optical thickness, etc.) can be performed with the optical coherence tomography (OCT) technique. However, speckle noise substantially deteriorates the accuracy of the measurements with this technique. We studied suppression of speckle noise for accurate measurement of backscattering signal and scattering coefficient with the OCT technique. Our results demonstrate that the precision of measurement of backscattering signals with the OCT technique can be 0.2% for homogeneously scattering media and 0.7% for skin, if spatial averaging of speckle noise is applied. This averaging allows us to achieve the precision of tissue scattering coefficient measurements of approximately +/-0.8%. This precision can be further improved by a factor of 2-3, upon optimization of OCT operating parameters.

Animals↗

Specificity of noninvasive blood glucose sensing using optical coherence tomography technique: a pilot study.

Noninvasive monitoring of blood glucose concentration in diabetic patients would significantly reduce complications and mortality associated with this disease. In this paper, we experimentally and theoretically studied specificity of noninvasive blood glucose monitoring with the optical coherence tomography (OCT) technique. OCT images and signals were obtained from skin of Yucatan micropigs and New Zealand rabbits. Obtained results demonstrate that: (1) several body osmolytes may change the refractive index mismatch between the interstitial fluid (ISF) and scattering centres in tissue, however the effect of the glucose is approximately one to two orders of magnitude higher; (2) an increase of the ISF glucose concentration in the physiological range (3-30 mM) may decrease the scattering coefficient by 0.22% mM(-1) due to cell volume change; (3) stability of the OCT signal slope is dependent on tissue heterogeneity and motion artefacts; and (4) moderate skin temperature fluctuations (+/- 1 degree C) do not decrease accuracy and specificity of the OCT-based glucose sensor, however substantial skin heating or cooling (several degrees C) significantly change the OCT signal slope. These results suggest that the OCT technique may provide blood glucose concentration monitoring with sufficient specificity under normal physiological conditions.

Animals↗

Reduction of infarct size by short-term pretreatment with atorvastatin.

Previous studies have suggested that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors attenuate ischemia-reperfusion injury by increasing the activity of endothelial nitric oxide synthase (eNOS). We assessed whether short-term treatment with atorvastatin reduces myocardial infarct size in the rat. Rats (male Sprague-Dawley) received atorvastatin 2 mg/kg per day (n = 9), 10 mg/kg per day (n = 8), or 75 mg/kg per day (n = 11), or placebo (n = 11) by gastric gavage for 3 days. Two additional groups received atorvastatin 10 mg/kg (n = 7) or placebo (n = 7) for 3 days and the nonselective nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), 15 mg/kg intravenously 15 min before surgery. All rats underwent 30 min of coronary artery occlusion followed by 180 min of reperfusion. Ischemic myocardium at risk was assessed with blue dye and infarct size by triphenyltetrazolium chloride. Ischemic myocardium at risk was comparable among groups. Infarct size, expressed as a percentage of the myocardium at risk, was significantly smaller in the atorvastatin 75 mg/kg group (22.6 +/- 2.8%; p = 0.035 vs. placebo) and atorvastatin 10 mg/kg (20.3 +/- 3.8%; p = 0.022 vs. placebo) compared with placebo (37.5 +/- 4.3%). The effect of atorvastatin 2 mg/kg was of smaller magnitude and did not reach statistical significance (infarct size 30.6 +/- 4.2% of the myocardium at risk). L-NAME abolished the protective effect of atorvastatin 10 mg/kg per day. Infarct size was 43.0 +/- 4.1% in the atorvastatin group and 39.4 +/- 3.3% in the placebo group (p = 0.503). In conclusion, short-term (3 days) atorvastatin (10-75 mg/kg/d) significantly reduced myocardial infarct size. The protective effect was completely abolished by L-NAME, strongly suggesting that this protective effect is mediated via the nitric oxide synthase pathway.

Animals↗

Feasibility study using surface-enhanced Raman spectroscopy for the quantitative detection of excitatory amino acids.

The release of excitatory amino acids (EAAs) from injured neurons has been associated with secondary injury following head trauma. The development of a rapid and sensitive method for the quantification of EAAs may provide a means for clinical management of patients affected by head trauma. We explore the potential application of surface-enhanced Raman spectroscopy (SERS) for rapid quantification of the concentration of EAAs in aqueous silver colloids. The EAAs glutamate (Glu) and aspartate (Asp) are released following head injury and have been observed to exhibit SERS spectra that should enable them to be distinguished in a complex aqueous media. Of the two EAAs, the concentration of Glu has been shown to be more indicative of injury to the central nervous system. Using 30-s scans and a 50-mW argon laser, aqueous Glu is quantifiable from 0.4 to 5 micromol/L and is spectrally distinguishable from Asp. In addition, initial in vivo microdialysis experiments suggest that this SERS system is capable of measuring chemical changes following head trauma in the rat brain. Compared with current high-performance liquid chromatography (HPLC) techniques for amino acid detection, the short scanning and processing time associated with the SERS approach enables measurement on a near-real-time basis, providing clinical information in anticipation of pharmaceutical intervention.

Animals↗

Wide-band spectral tuning of heat receptors in the pit organ of the copperhead snake (Crotalinae).

Receptors located in the facial pit organ of certain species of snake signal the presence of prey. Infrared radiation is an effective stimulus suggesting that these receptors may be low-threshold temperature receptors. We recorded from the nerve innervating the pit organ of snakes belonging to the family of Crotalinae while stimulating the receptive area with well-defined optical stimuli. The objective was to determine the sensitivity of these receptors to a wide range (0.400-10.6 micro m) of optical stimuli to determine if a temperature-sensitive or photosensitive protein initiated signal transduction. We found that receptors in the pit organ exhibited a unique broad response to a wide range of electromagnetic radiation ranging from the near UV to the infrared. The spectral tuning of these receptors parallels closely the absorption spectra of water and oxyhemoglobin, the predominant chromophore in tissue. Our results support the hypothesis that these are receptors activated by minute temperature changes induced by direct absorption of optical radiation in the thin pit organ membrane.

Afferent Pathways↗

Luminescent lanthanide chelate contrast agents and detection of lesions in the hamster oral cancer model.

Lanthanide chelates are a somewhat unique class of molecules that have proven to be useful in the biomedical field due to their extremely large Stokes' shift and long fluorescent lifetimes. The ability of these molecules to produce fluorescence in the low- or zero-back-ground regime makes this class of molecules excellent candidates for use as contrast agents for a wide variety of applications in biological settings. Here we present the preparation, spectroscopic characterization, and application of a new terbium chelate contrast agent, based on the 1,4,7,10-tetraazacyclododecane macrocycle (cyclen), for detection of early-stage malignant lesions in the Syrian hamster cheek pouch. Tb-P(CTMB) delivers bright blue-green luminescence when excited with low photon fluxes of UV light. As a pilot study, the DMBA-treated Golden Hamster Cheek pouch epithelial cancer model was employed and Tb-P(CTMB) was used as a topical agent for the visual detection of diseased tissue. In this preliminary study the agent tended to associate with early-stage malignant lesions, suggesting that Tb-P(CTMB) could be used as a contrast agent to aid in identifying early-stage oral cancer lesions.

Animals↗

Optoacoustic technique for noninvasive monitoring of blood oxygenation: a feasibility study.

Replacement of invasive monitoring of cerebral venous oxygenation with noninvasive techniques offers great promise in the management of life-threatening neurologic illnesses including traumatic brain injury. We developed and built an optoacoustic system to noninvasively monitor cerebral venous oxygenation; the system includes a nanosecond Nd:YAG laser and a specially designed optoacoustic probe. We tested the system in vitro in sheep blood with experimentally varied oxygenation. Our results demonstrated that (1) the amplitude and temporal profile of the optoacoustic waves increase with blood oxygenation in the range from 24% to 92%, (2) optoacoustic signals can be detected despite optical and acoustic attenuation by thick bone, and (3) the system is capable of real-time and continuous measurements. These results suggest that the optoacoustic technique is technically feasible for continuous, noninvasive monitoring of cerebral venous oxygenation.

Feasibility Studies↗

Noninvasive blood glucose monitoring with optical coherence tomography: a pilot study in human subjects.

OBJECTIVE: To study the feasibility of noninvasive blood glucose monitoring using optical coherence tomography (OCT) technique in healthy volunteers. RESEARCH DESIGN AND METHODS: An OCT system with the wavelength of 1,300 nm was used in 15 healthy subjects in 18 clinical experiments. Standard oral glucose tolerance tests were performed to induce changes in blood glucose concentration. Blood samples were taken from the right arm vein every 5 or 15 min. OCT images were taken every 10-20 s from the left forearm over a total period of 3 h. The slope of the signals was calculated at the depth of 200-600 micro m from the skin surface. RESULTS: A total of 426 blood samples and 8,437 OCT images and signals were collected and analyzed in these experiments. There was a good correlation between changes in the slope of noninvasively measured OCT signals and blood glucose concentrations throughout the duration of the experiments. The slope of OCT signals changed significantly (up to 2.8% per 10 mg/dl) with variation of plasma glucose values. The good correlation obtained between the OCT signal slope and blood glucose concentration is due to the coherent detection of backscattered photons, which allows measurements of OCT signal from a specific tissue layer without unwanted signal from other tissue layers. CONCLUSIONS: This pilot study demonstrated the capability of the OCT technique to monitor blood glucose concentration noninvasively in human subjects. Further studies with a larger number of subjects including diabetic subjects are planned to validate these preliminary results.

Adult↗