Laser Doppler Blood Flow Meter Research Articles

Defective Myogenic Response of Retinal Vessels Is Associated With Accelerated Onset of Retinopathy in Type 1 Diabetic Individuals.

We seek to identify pathogenic mechanisms for diabetic retinopathy that can become therapeutic targets beyond hyperglycemia and hypertension. We investigated if a defective myogenic response of retinal arteries to increased perfusion pressure, which exposes capillaries to increased pressure and flow, is associated with the onset of clinical retinopathy. We examined prospectively the incidence of retinopathy in type 1 diabetic individuals tested 4 years earlier for the retinal arterial myogenic response, and in a cross-sectional study the prevalence of defective myogenic response in type 1 patients who had diabetic retinopathy. Among these, we contrasted early-onset (after 15 ± 2 years of diabetes, E-DR; n = 5) to late-onset (after 26 ± 3 years of diabetes, L-DR; n = 7) retinopathy. We measured the myogenic response using a laser Doppler blood flowmeter after a change in posture from sitting to reclining, which increases retinal perfusion pressure. Five of seven participants who 4 years prior had a defective myogenic response had now developed clinical retinopathy; as compared with only one of six participants who 4 years prior had a normal response (P = 0.10). In the cross-sectional study, all participants had normal retinal hemodynamics at steady state. In response to the postural change, only the E-DR group showed defective myogenic response (P = 0.005 versus controls, P = 0.02 versus L-DR) and abnormally high retinal blood flow (P = 0.016 versus controls). In type 1 diabetic patients, a defective myogenic response of retinal arteries to pressure is not required for the development of clinical retinopathy, but is prominently associated with an accelerated onset of retinopathy.

Abstract P5-15-13: Restoration by compression therapy of skin blood perfusion levels decreased during breast cancer chemotherapy, alleviating peripheral neuropathy

Abstract <Background> Nanoparticle albumin-bound paclitaxel (nab-PTX) has become a key drug used in chemotherapy for breast cancer, but it often causes adverse effects such as peripheral neuropathy (PN). No effective prophylactic management has so far been established. We have applied a "3S" approach to prevent and treat PN based on two concepts: compression therapy using stockings and sleeves, and medication therapy using selected prophylactic medications. We previously reported better CTCAE v4.0 PN grades and notably superior nab-PTX dose maintenance in a 3S group compared to a control group. However, little is known about the effects of compression therapy on a patient’s level of skin blood perfusion; it is also unknown whether any such effects might vary by 1) PN grade or 2) the number of nab-PTX cycles. <Patients and Methods> To establish whether a compression therapy-skin perfusion relationship exists, the skin perfusion of the lower limbs was measured before and after stocking use in a 3S prophylactic treatment group for nab-PTX therapy (n=44), and in a control group of healthy volunteers (n=50). The skin perfusion was measured using a laser Doppler blood flow meter with an integrated probe (NL-101 Nahri Nexis Japan). To find how compression therapy affects skin perfusion by PN grade, the 3S group was subdivided into three PN grade subgroups (n = 12 for Grade 0, n = 20 for Grade 1, and n = 12 for Grades 2 and 3 combined). To find how compression therapy affects skin perfusion by number of nab-PTX treatment cycles undergone by patients, the 3S group was subdivided into the following three subgroups: 1 to 5 cycles of nab-PTX treatment (first period group; 1P, n=18), 6 to 10 cycles (second period group; 2P, n=16), and more than 10 cycles (third period group; 3P, n=12). <Results> In the control group of healthy volunteers, stocking use tended to increase the median skin perfusion level (mL/min/100g) from 10.9 ± 3.8 to 11.8 ± 4.3 (p=0.06). Interestingly, the median skin perfusion level for the 3S group as a whole significantly increased from 8.7 ± 3.3 before stocking use to 11.3 ± 3.8 after stocking use (p< 0.001). When examining the effects of stocking use on skin perfusion by PN grade, the increase in median skin perfusion level was significant in the Grade 0 subgroup (8.2 ± 2.7 to 12.4 ± 4.5, p=0.005), in the Grade 1 subgroup (8.3 ± 3.8 to 10.4 ± 4.0, p=0.0499), and in the Grades 2 and 3 subgroup (7.9 ± 2.3 to 10.6 ± 2.4, p=0.005). When examining the effects of stocking use on skin perfusion by number of treatment cycles, the increase in median skin perfusion level was significant in the 1P subgroup (7.9 ± 3.0 to 11.4 ± 4.8, p=0.007) and in the 2P (7.9 ± 2.9 to 10.8 ± 2.9, p=0.005), but not in the 3P (9.3 ± 3.5 to 10.8 ± 3.2, p=0.15). <Conclusion> This study demonstrated that the skin perfusion of the lower limbs is decreased following nab-PTX chemotherapy, and also that the skin perfusion is improved by compression therapy. Compression therapy appeared to successfully restore the skin perfusion levels across every grade of chemotherapy-induced PN. Therefore, our 3S approach is suitable for alleviating CIPN by proactively maintaining skin perfusion from the beginning of nab-PTX therapy. Citation Format: Tsuyoshi Ohno, Takashi Mine, Hiroki Yoshioka, Mikiko Kosaka, Kazuhiro Matsuda, Maiko de Kerckhove, Charles de Kerckhove. Restoration by compression therapy of skin blood perfusion levels decreased during breast cancer chemotherapy, alleviating peripheral neuropathy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-13.

Relationship of peripheral neuropathy grades with increase of skin perfusion by compression therapy for breast cancer patients.

182 Background: Chemotherapy-induced peripheral neuropathy (CIPN) has become a substantial problem because of specific cytotoxic agents such as nab-paclitaxel, oxaliplatin, and eribulin. In addressing CIPN-related side effects caused by nab-PTX, we previously reported better CTCAE v4.0 grades and superior nab-PTX dose maintenance in breast cancer treatment adopting our 3S approach. Our 3S approach combines compression therapy (stockings and sleeves applied 24 hours from the beginning of nab-PTX administration) with medication therapy (selected prophylactic medications goshajinkigan, lafutidine, and mecobalamin applied over the course of treatment). In revisiting how stocking use restored skin perfusion levels decreased by nab-PTX chemotherapy, we examined whether the skin perfusion increases differ by CIPN grade. Methods: Using a laser Doppler blood flow meter with integrated probe (NL-101 Nahri Nexis Japan), we measured the skin perfusion of the lower limbs before and after stocking use across four groups: three groups of 3S prophylactics-treated nab-PTX patients divided by CIPN grade (Grade 0 [G0, n=12], Grade 1 [G1, n=20], Grades 2 and 3 combined [G2+3, n=12]), and one control group of healthy volunteers (GH, n=50). Results: In the control group (GH), the mean increase in skin perfusion level (mL/min/100g) after wearing stockings was 0.90 (SD= 3.36). For the 3S prophylactic treatment patients, the mean increase was 4.25 (4.98) in the G0 group, 2.11 (4.93) in the G1 group, and 2.69 (2.53) in the G2+3 group. ANOVA analysis indicated a significant difference in skin perfusion increase among the groups (p=0.0493). Analysis between the groups indicated significance in the G0 group increase over the control group increase (p=0.0255). Conclusions: CIPN was previously shown to decrease skin perfusion; in the current study skin perfusion responsiveness to stockings differed significantly between chemotherapy patients and healthy volunteers. Restorative skin perfusion increase is potentially related with alleviating CIPN grade, for which further evaluation is needed.

Development of an assay method to search for compounds inhibiting stress-enhanced allergy

Allergic disorders, such as atopic dermatitis and asthma, become severe or relapse due to stress. As stress is an important factor affecting blood flow (BF), we developed a new assay system based upon our findings on BF decrease in the induction phase of allergy in mice sensitized using egg-white lysozyme (HEL) [1, 2]. Male ddY mice were sensitized i.p. with 12.5, 25 or 50 µg/head of HEL emulsified in complete Freund's adjuvant on 0 day. BF of the venous microcirculation of the tail hypodermic of un-anesthetized mouse was monitored using a Laser Doppler BF Meter of the contact type as previously described [1]. The stress load was given using a modification of the method of Castilla-Ortega E et al [3]. Mice in the stressed groups were restrained 1h or 1.5h daily for 5 – 10 consecutive days in a modified 50 ml clear polystyrene conical centrifuge tube (2.8 cm x11.2 cm in length) with multiple air holes for ventilation. No significant difference of BF decreases between previously reported sensitized mice [1] and stress-enhanced sensitized mice was found. Therefore, we examined the quantity of HEL needed for the sensitization and concluded that we could evaluate stress-enhanced allergy even if the amount of HEL was reduced to 12.5 µg/head. With respect to the stress exposure time, BF showed a significant decrease by the 8th to 10th day on exposure for 60 min/day and by the 5th to 7th day on exposure for 90 min/day. We finally established 90 min/day for 7 days (every other day) as being suitable for an assay system of stress-enhanced allergy. Using this novel assay system, we evaluated natural herbal medicines that are clinically used to treat stress or allergic disorders. Our model should be useful for identifying potential anti-stress-enhanced allergy drugs.

The Relationship Between the Grade of Peripheral Neuropathy and the Skin Blood Perfusion in Chemotherapy-Induced Peripheral Neuropathy Patients, and the Effects of Compression Therapy

ABSTRACT Aim: Nanoparticle albumin-bound paclitaxel (nab-PTX) has become a key drug used in chemotherapy for breast cancer, but it often causes adverse effects such as peripheral neuropathy (PN). No effective prophylactic management has so far been established. We have applied a “3S” approach to prevent and treat PN based on two concepts: compression therapy using stockings and sleeves, and medication therapy using selected prophylactic medications. We previously reported better CTCAE v4.0 grades and notably superior nab-PTX dose maintenance in a 3S group compared to a control group with no prophylactic treatment. However, little is known about the effects of compression therapy on the relationship between PN and the skin blood perfusion. Methods: The skin perfusion of the lower limbs was measured before and after stocking use in a 3S prophylactic treatment group for nab-PTX therapy (n = 50), and in a control group of healthy volunteers (n = 50). The 3S group was subdivided by PN grade for a subsequent analysis (n = 18 for Grade 0, n = 22 for Grade 1 and n = 10 for Grades 2 and 3 combined). The skin perfusion was measured using a laser Doppler blood flow meter with an integrated probe (NL-101 Nahri Nexis Japan). Results: In the control group of healthy volunteers, stocking use tended to increase the median skin perfusion level (mL/min/100g) from 10.9 ± 3.8 to 11.8 ± 4.3. Interestingly, the median skin perfusion level for the 3S group as a whole significantly increased from 8.7 ± 3.3 before stocking use to 11.3 ± 3.8 after stocking use (p Conclusions: This study demonstrated that the skin perfusion of the lower limbs is decreased following nab-PTX chemotherapy, and also that compression therapy can successfully restore the skin perfusion levels in nab-PTX patients across every grade of peripheral neuropathy. This apparent restoration in skin perfusion may increase the drug clearance, which could potentially alleviate peripheral neuropathy. Disclosure: All authors have declared no conflicts of interest.

Importance of optimal local uterine blood flow for implantation.

The aim of this study was to determine whether uterine blood flow is an effective parameter to anticipate uterine receptivity. The local uterine blood flow was measured in the endometrium and on the outside of the uterus in mice during the early stage of pregnancy and an implantation failure mouse model using transient and local suppression of signal transducer and activator of transcription-3 activity during implantation. The local uterine blood flow was dramatically increased after mating and was decreased towards the time of implantation. The local uterine blood flow at 2.5 days post-coitus in signal transducer and activator of transcription-3 decoy transferred mice was significantly higher than in control mice. However, the range of individual values was too wide to find a cut-off point. It is necessary to decrease local uterine blood flow after ovulation to prepare the opening implantation window. The optimal local uterine blood flow is regulated by time events during pregnancy. The range of individual values of uterine blood flow is wide using a laser Doppler blood flow meter. This parameter itself may not be an appropriate parameter to evaluate the prospect of uterine receptivity.

Human Umbilical Cord Mesenchymal Stem Cells Transplantation Promotes Cutaneous Wound Healing of Severe Burned Rats

BackgroundSevere burns are a common and highly lethal trauma. The key step for severe burn therapy is to promote the wound healing as early as possible, and reports indicate that mesenchymal stem cell (MSC) therapy contributes to facilitate wound healing. In this study, we investigated effect of human umbilical cord MSCs (hUC-MSCs) could on wound healing in a rat model of severe burn and its potential mechanism.MethodsAdult male Wistar rats were randomly divided into sham, burn, and burn transplanted hUC-MSCs. GFP labeled hUC-MSCs or PBS was intravenous injected into respective groups. The rate of wound closure was evaluated by Image Pro Plus. GFP-labeled hUC-MSCs were tracked by in vivo bioluminescence imaging (BLI), and human-specific DNA expression in wounds was detected by PCR. Inflammatory cells, neutrophils, macrophages, capillaries and collagen types I/III in wounds were evaluated by histochemical staining. Wound blood flow was evaluated by laser Doppler blood flow meter. The levels of proinflammatory and anti-inflammatory factors, VEGF, collagen types I/III in wounds were analyzed using an ELISA.ResultsWe found that wound healing was significantly accelerated in the hUC-MSC therapy group. The hUC-MSCs migrated into wound and remarkably decreased the quantity of infiltrated inflammatory cells and levels of IL-1, IL-6, TNF-α and increased levels of IL-10 and TSG-6 in wounds. Additionally, the neovascularization and levels of VEGF in wounds in the hUC-MSC therapy group were markedly higher than those in other control groups. The ratio of collagen types I and III in the hUC-MSC therapy group were markedly higher than that in the burn group at indicated time after transplantation.ConclusionThe study suggests that hUC-MSCs transplantation can effectively improve wound healing in severe burned rat model. Moreover, these data might provide the theoretical foundation for the further clinical application of hUC-MSC in burn areas.

Blood flow measurement and clinical usefulness of the temporal fascial scar tissue flap and the periosteal scar tissue flap in posterior canal wall reconstructed tympanoplasty for the mastoid cavity problem in the postoperative ear

In the postoperative ear, following reconstructive tympanoplasty for a mastoid cavity problem, a very important key is to maintain a stable reconstructed posterior canal wall with the bone plate and cartilage in the posterior canal wall. The authors manage reconstruction of the posterior canal wall with the temporal fascial scar tissue flap (TFSF) and the temporal periosteal scar tissue flap (TPSF) to ensure obtaining a stable posterior canal wall and a tympanic membrane graft. Well-vascularized TFSF and TPSF enable us to acquire a solid reconstructed posterior canal wall because of the secure blood supplies to the flaps. In order to investigate the blood supplies of TFSF and TPSF, we employed laser Doppler blood flowmeters and measured blood flow in the flaps in 20 cases of posyoperative ears treated for a mastoid cavity problem. The blood supplies to both flaps were good, with the blood supply to the TFSF being statistically better than in the case of the TPSF. These findings suggested that the TFSF and TPSF were a reliable source of local well-vascularized tissue which were pliable and could facilitate the creation of a stable posterior canal wall. Furthermore it seems the good blood supply was linked to the prompt postoperative healing, the avoidance of postoperative infection, and good hearing improvement postoperatively.

Useful method to monitor the physiological effects of alcohol ingestion by combination of micro-integrated laser Doppler blood flow meter and arm-raising test

Alcohol has a variety of effects on the human body, affecting both the sympathetic and parasympathetic nervous system. We examined the peripheral blood flow of alcohol drinkers using a micro-integrated laser Doppler blood flow meter (micro-electromechanical system blood flow sensor). An increased heart rate and blood flow was recorded at the earlobe after alcohol ingestion, and we observed strong correlation between blood flow, heart rate, and breath alcohol content in light drinkers; but not heavy drinkers. We also found that the amplitude of pulse waves measured at the fingertip during an arm-raising test significantly decreased on alcohol consumption, regardless of the individual's alcohol tolerance. Our micro-electromechanical system blood flow sensor successfully detected various physiological changes in peripheral blood circulation induced by alcohol consumption.

Systemic Delivery Systems of Angiogenic Gene by Novel Bubble Liposomes Containing Cationic Lipid and Ultrasound Exposure

Recently, we developed polyethyleneglycol (PEG)-modified liposomes (Bubble liposomes; BLs) entrapping ultrasound (US) gas and reported that the combination of BL and US exposure was an effective tool for the delivery of pDNA directly into skeletal muscles of an ischemic hindlimb model with local injection. To achieve gene delivery to deeper tissues, we attempted to prepare novel Bubble liposomes which were able to be loaded with pDNA and useful for systemic injection. We prepared BLs using cationic lipid and analyzed the interaction with the BLs and pDNA using flow cytometry. The solution of pDNA-loaded BLs (p-BLs) was further injected into the tail vein of hindlimb ischemia model mice, and transdermal US exposure was applied to ischemic hindlimb. The effects of transfection on angiogenic factors were investigated by real-time PCR. Blood flow was determined using a laser Doppler blood flow meter. The interaction with BLs and pDNA increased in the presence of DOTAP and short PEG chains and resulted in increased stability of pDNA in the serum. Transfection with pDNA encoding the bFGF gene using p-BLs and US induced various angiogenic factors and improved the blood flow. The gene delivery system into the ischemic hindlimb using the combination of p-BLs and US exposure could be an effective tool for angiogenic gene therapy via systemic injection.

Leptin administration alleviates ischemic brain injury in mice by reducing oxidative stress and subsequent neuronal apoptosis

Recent research has indicates that leptin plays a protective role in traumatic brain injury. We studied the protective effect of leptin on cerebral ischemia/reperfusion injury by using mice transient focal cerebral ischemia/reperfusion injury model. The distribution of 125I-leptin in the mouse brain was assessed by radioimmunoassay method. Mouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for two hours followed by 24 hours reperfusion. The neurologic deficits and infarct volume were determined using the Longa's score and 2,3,5-triphenyltetrazolium chloride staining, respectively. Regional cerebral blood flow was monitored by a laser-Doppler blood flowmeter. The levels of malondialdehyde, nitric oxide, nitric oxide synthase, and superoxide dismutase were detected according to respective assay kit. The histologic changes and neuronal apoptosis were observed with hematoxylin and eosin and transferase-mediated dUTP-biotin nick end labeling staining, respectively. The expression of B-cell lymphoma/leukemia-2 (Bcl-2) and cysteineasparateprotease-3 (caspase-3) were investigated by Western blot and real-time polymerase chain reaction assay. Leptin decreased infarct volume and neurologic defects and improved regional cerebral blood flow and microvascular branch blood flow after injury. The malondialdehyde and nitric oxide levels were reduced, and superoxide dismutase level was increased after leptin treatment, which also minimized histologic changes and neuronal apoptosis, led to the upregulation of Bcl-2 and downregulation of caspase-3 expression after injury. Peripherally administered leptin crossed the blood-brain barrier and was distributed into multiple regions of the brain; in the brain, leptin directly alleviated the injury-evoked damages by reducing oxidative stress and neuronal apoptosis.

Tissue Blood Flow Reductions Induced by Remifentanil in Rabbits and the Effect of Naloxone and Phentolamine on These Changes

The purpose of this study was to investigate the effects of naloxone and phentolamine on the blood flow changes in rabbit oral tissue induced by remifentanil during sevoflurane anesthesia. Male Japan White rabbits were anesthetized with sevoflurane under mechanical ventilation. Remifentanil was continuously infused at a rate of 0.4 μg/kg/min. Naloxone 0.01 mg/kg or phentolamine 0.01 mg/kg was administered during remifentanil infusion. Observed variables were systolic and diastolic blood pressures, mean arterial pressure, heart rate, common carotid artery blood flow, tongue mucosal blood flow, mandibular bone marrow blood flow, masseter muscle blood flow, and upper and lower alveolar tissue blood flows. The common carotid artery blood flow was monitored continuously using an ultrasonic blood flowmeter. Tongue mucosal blood flow was monitored continuously using a laser Doppler blood flowmeter. Mandibular bone marrow blood flow, masseter muscle blood flow, and upper and lower alveolar tissue blood flows were measured using a hydrogen clearance tissue blood flowmeter. One-way analysis of variance for repeated measurements followed by the Student-Newman-Keuls test was used. Remifentanil produced decreases in the heart rate, systolic blood pressure, and common carotid artery blood flow by about 15% and mandibular bone marrow blood flow, masseter muscle blood flow, and upper and lower alveolar tissue blood flows by about 30%. In the naloxone group, all variables recovered after naloxone administration. In contrast, in the phentolamine group, tissue blood flow recovered, whereas heart rate, systolic blood pressure, and common carotid artery blood flow did not recover after phentolamine administration. Remifentanil deceased oral tissue blood flow and systemic hemodynamic variables. Naloxone and phentolamine produced a recovery of oral tissue blood flow with and without systemic hemodynamic recovery, respectively.

The effect of atherosclerosis‐induced chronic bladder ischemia on bladder function in the rat

To develop a rat model of atherosclerosis-induced chronic bladder ischemia and investigate the effect of chronic bladder ischemia on voiding behavior and bladder function. Adult male rats were divided into three groups. The arterial injury (AI) group underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet. The sham group underwent sham operation and received a 2% cholesterol diet. The control group received a regular diet. After 8 weeks, a metabolic cage study and cystometry were performed without anesthesia. Bladder blood flow was measured using a laser Doppler blood flowmeter. Histological examination of the iliac arteries and the bladder was performed. The bladder was also processed for immunohistochemical staining of oxidative stress markers. The metabolic cage study showed that in the AI group, voiding frequency significantly increased while voided volume significantly decreased. Cystometry showed that the frequency of reflex bladder contractions was significantly higher in the AI group. Filling-induced decrease in bladder blood flow was the greatest in the AI group. Histological study showed that in the AI group alone, atherosclerotic occlusion occurred in the iliac arteries as well as in the downstream bladder microvessels. Oxidative stress marker positive cells were more prevalent in the AI bladder than in the other bladders. Combined with a high-cholesterol diet, endothelial injury of iliac arteries induced arterial occlusive disease in the downstream vessels and consequent bladder ischemia in rats. This model of chronic bladder ischemia showed detrusor overactivity manifested as an increase in voiding frequency.

Fascial and Periosteal Flaps for Postoperative Otitis Media

Objective: It is very important to maintain a stable reconstructed posterior canal wall in the posterior canal wall reconstructed tympanoplasty for the postoperative chronic otitis media (OM) case. The authors treat reconstructed posterior canal wall with the temporal fascial flap (TFF) and the temporal periosteal flap (TPF). Method: In order to investigate the blood supplies of TFF and TPF, we employed Laser Doppler blood flow meters and measured that in 15 cases of postoperative chronic otitis media. Results: Both blood supplies were comparatively well, and TFF’s blood supplies were statistically better than those of TPF. Conclusion: These findings suggested that the TFF and TPF were reliable sources of local well-vascularized tissue to be extremely pliable and facilitate creation of a stable posterior canal wall in the case of postoperative OM.

Use of a simple arm-raising test with a portable laser Doppler blood flow meter to detect dehydration

Using micro electromechanical systems (MEMS) technologies, the authors have developed the world’s smallest, lightest, and least power-consuming laser Doppler blood flow meter. Unlike commercial fibre-type blood flow instruments, the new blood flow meter is invulnerable to any movements of the person wearing it and has a wireless transmitter. Utilizing the characteristics of the blood flow meter, the authors attempted to detect dehydration by having a subject simply raise an arm (arm-raising test) with the flow meter attached to a fingertip. Healthy young volunteers (20 men and two women, mean age 22.9, age range 21–27 years) were instructed to perspire in a sauna until they became dehydrated. The target dewatering ratio was 2 per cent, which was calculated from the body weight measured using a weight scale. Four markers were compared: mean blood flow (MBF) before arm-raising, MBF during arm-raising, maximum amplitude (MA) of the pulse wave during arm-raising, and inclination of reflex (IR) wave calculated from the recorded blood flow data for the non-dehydrated (before sauna) and dehydrated (3 h after sauna) states in the arm-raising test. Each of the mean total markers (MBF during arm-raising, MA, and IR) was significantly lower ( P < 0.05) during the dehydrated state than the non-dehydrated. These results suggest that three markers could detect dehydration and the blood flow meter devised has the potential to be used as a portable device for detecting dehydration.

Fractal Dimension Characterization of in-vivo Laser Doppler Flowmetry signals

Laser Doppler Blood Flow meter uses tissue backscattered light to non-invasively assess the blood flow rate. qualitatively. As there is large spatial variability and the temporal heterogeneity in tissue microvasculature, the measured blood flow rate is expressed in relative units. A non-linear approach in order to understand the dynamics of the microcirculation led to the fractal characterization of the blood flow signals. The study presented in the paper aims to analyze the fractal behavior of Laser Doppler Flow (LDF) signals and to quantitatively estimate the fractal dimension of waveforms using Box-Counting method. The measured Fractal dimension is an estimate of temporal variability of tissue perfusion. The rate at which fractal dimension varies as a function of location between individuals, exhibits a weak correlation with time. Further studies with a larger number of subjects are necessary to test the generality of the findings and if changes in dimension are reproducible in given individuals. In conclusion, the fractal dimension determined by Box-counting method may be useful for characterizing LDF time series signals. Future experiments evaluating whether the technique can be used to quantify microvascular dysfunction, as commonly occurring in conditions such as Diabetes, Raynaud's phenomenon, Erythromelalgia and Achenbach syndrome needs to be evaluated.

Changes of Color and Blood Flow of the Tongue in the Mini-swine of Immune Hepatic Injury

To investigate color and microvascular blood flow of the tongue in the mini-swine with immune hepatic injury. Six Chinese mini-swine for experimental use, 3 males and 3 females, were randomly divided into two groups, normal group and model group, 3 swine in each group. The swine in the model group was administrated by injection of 5 mg/kg ConA into the vein of auricular back, once every other day, 3 times each week, for 2 weeks in total. The animal in the control group was administrated with equal volume of saline. At 9 o'clock in the morning of the 15th day of the experiment, each swine was anesthetized with intramuscular injection of 9 ml 2.5% pentobarbital sodium and 3 ml Maleate, and then picture of the tongue was taken, microvascular blood flow on the tongue and the liver was detected with a laser Doppler blood flowmeter; Blood was taken from the precaval vein. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil) and total protein (TP) were determined; Pathological changes of the liver and tongue tissues were investigated by means of HE staining; Serum TNF-alpha content was detected with ELISA assay. In the mini-swine with immune hepatic injury induced by ConA, the tongue color showed cyanotic color, microvascular perfusion in the liver and the tongue, and partial pressure of oxygen in the tongue tissue significantly decreased; and the microcirculatory perfusion of the tongue was significantly correlated with that of the liver and the HIS color spatial value of the tongue; Serum TNF-alpha content significantly increased. The mini-swine with immune hepatic injury induced by ConA conforms to pathological characteristics of immune hepatic injury. Formation of the cyanotic tongue is related with microcirculatory disturbance of the tongue, which can indirectly reflect hepatic microcirculatory state in the immune hepatic injury.

Delivery of an Angiogenic Gene into Ischemic Muscle by Novel Bubble Liposomes Followed by Ultrasound Exposure

To develop a safe and efficient gene delivery system into skeletal muscle using the combination of Bubble liposomes (BL) and ultrasound (US) exposure, and to assess the feasibility and the effectiveness of BL for angiogenic gene delivery in clinical use. A solution of luciferase-expressing plasmid DNA (pDNA) and BL was injected into the tibialis (TA) muscle, and US was immediately applied to the injection site. The transfection efficiency was estimated by a luciferase assay. The ischemic hindlimb was also treated with BL and US-mediated intramuscular gene transfer of bFGF-expressing plasmid DNA. Capillary vessels were assessed using immunostaining. The blood flow was determined using a laser Doppler blood flow meter. Highly efficient gene transfer could be achieved in the muscle transfected with BLs, and US mediated the gene transfer. Capillary vessels were enhanced in the treatment groups with this gene transfer method. The blood flow in the treated groups with this gene transfer method quickly recovered compared to other treatment groups (non-treated, bFGF alone, or bFGF+US). The gene transfer system into skeletal muscle using the combination of BL and US exposure could be an effective means for angiogenic gene therapy in limb ischemia.

Integrated Laser Doppler Blood Flowmeter Designed to Enable Wafer-Level Packaging

The authors propose a new sensor structure for an integrated laser Doppler blood flowmeter that consists of two silicon cavities with a PD and laser diode inside each cavity. A silicon lid formed with a converging microlens completes the package. This structure, which was achieved using micromachining techniques, features reduced optical power loss in the sensor, resulting in its small size and significantly low power consumption. Measurements using a model tissue blood flow system confirmed that the new sensor had high linearity and a wide dynamic range for measuring tissue blood flow.

Blood flow in denture-supporting maxillary mucosa in response to simulated mastication by loading

The purpose of this study was to determine the effect of number of chewing strokes on change in blood flow in denture-supporting maxillary mucosa. Subjects consisted of 11 healthy dentate men. Mastication was simulated by intermittent loading (10 N, 1/0.75 Hz) on a lateral area of the hard palate using a 2-cm(2) test plate. Loading duration was set at 1, 4, 8 or 12 min (80, 320, 640 or 960 chewing strokes). A non-contact laser Doppler blood flow meter was used to determine change in blood flow and time taken for recovery to 110% of the pre-loading value. Mean blood flow at pre-loading and at each duration of intermittent loading were compared using a repeated measures ANOVA (α=0.05) and the Dunnett test. Recovery times for each loading duration were compared using a one-way ANOVA (α=0.05) and the Bonferroni-test. Three subjects showed no increase in mean blood flow with loading. Eight subjects consistently showed an increase in mean blood flow during intermittent loading relative to at pre-loading. Duration of loading yielded no significant difference in mean blood flow. Significant differences were observed in recovery time between at after 8 min loading and at after the other 3 loading (1, 4, and 12 min loading) durations. Number of simulated chewing strokes showed no influence on mean blood flow during intermittent loading in denture-supporting mucosa. It did, however, affect recovery time taken for blood flow to return to its pre-loading level.