Effects of anthracycline chemotherapy and Kuan-Sin-Yin on the spectral indices of arterial pulse waveforms in breast cancer patients.

The vascular structure and function are potentially useful biomarkers for tumor detection. Treatment with chemotherapeutic agents may impair vascular function and increase the risk of cardiovascular disease. This study aimed to use noninvasive pulse waveform measurements to identify differences in the frequency-domain indices of the pulse waveform in breast-cancer patients following anthracycline chemotherapy between with (Group KSY) and without (Group NKSY) receiving Kuan-Sin-Yin (KSY) treatment.Radial blood pressure waveform (BPW) signals were measured noninvasively for 3 minutes in 31 patients, and the FACT-G, BFI-T, and EORTC QLQ-C30 questionnaires were administered. The following pulse indices were calculated for 10 harmonics: the amplitude proportion and its coefficient of variation, and the phase angle and its standard deviation.The changes in spectral BPW indices were more prominent in Group NKSY than in Group KSY, especially for the decreases in BPW variability indices. Scores on the FACT-G, BFI-T, and EORTC QLQ-C30 questionnaires suggested that the quality of life following chemotherapy was better in Group KSY.The identified decreases in pulse variability indices could be related to the greater impairment of regulatory activities in Group NKSY. The present findings may be meaningful in developing techniques with advantages such as being noninvasive and time-saving to evaluate the blood supply and physiological conditions following chemotherapy or other treatment strategies in cancer patients.

Discrimination of the Cognitive Function of Community Subjects Using the Arterial Pulse Spectrum and Machine-Learning Analysis.

Early identification of cognitive impairment would allow affected patients to receive care at earlier stage. Changes in the arterial stiffness have been identified as a prominent pathological feature of dementia. This study aimed to verify if applying machine-learning analysis to spectral indices of the arterial pulse waveform can be used to discriminate different cognitive conditions of community subjects. 3-min Radial arterial blood pressure waveform (BPW) signals were measured noninvasively in 123 subjects. Eight machine-learning algorithms were used to evaluate the following 4 pulse indices for 10 harmonics (total 40 BPW spectral indices): amplitude proportion and its coefficient of variation; phase angle and its standard deviation. Significant differences were noted in the spectral pulse indices between Alzheimer's-disease patients and control subjects. Using them as training data (AUC = 70.32% by threefold cross-validation), a significant correlation (R2 = 0.36) was found between the prediction probability of the test data (comprising community subjects at two sites) and the Mini-Mental-State-Examination score. This finding illustrates possible physiological connection between arterial pulse transmission and cognitive function. The present findings from pulse-wave and machine-learning analyses may be useful for discriminating cognitive condition, and hence in the development of a user-friendly, noninvasive, and rapid method for the early screening of dementia.

Involvement of 8-O-acetylharpagide for Ajuga taiwanensis mediated suppression of senescent phenotypes in human dermal fibroblasts.

Herbal medicines are attractive agents for human care. In this study, we found that the alcohol extract of Ajuga taiwanensis (ATE) screened from a chemical bank exhibited potent capacity for suppressing senescence associated biomarkers, including SA-ß-gal and up-regulated p53 in old human dermal fibroblasts (HDFs) without induction of significant cytotoxicity up to 100 µg/ml. Concomitantly, cells re-entered the cell cycle by reducing G1 phase arrest and increasing cell growth rate. The ATE was further partitioned to obtain the sub-fractions of n-butanol (BuOH), ethyl acetate (EA) and water. The BuOH and water sub-fractions exhibited less effects on prohibition of cell growth than the EA sub-fraction. All of these sub-fractions exhibited the ability on suppressing SA-ß-gal and p53 of old HDFs as low as 5-10 µg/ml. Under the activity guided fractionation and isolation, a major active constituent named AT-1 was isolated. The AT-1 was further identified as 8-O-acetylharpagide by structural analysis, and it could suppress SA-ß-gal and p53 of old HDFs below 10 µM. In addition, the intracellular reactive oxygen species (ROS) levels of old HDFs were suppressed by ATE, the sub-fractions of BuOH and water, and AT-1. However, the EA sub-fraction showed little ability on suppression of ROS. Furthermore, we performed an in vivo study using aging mice to be fed with ATE and the sub-fractions followed by immunohistochemical (IHC) staining. The expression of p53 and SA-ß-gal was significantly reduced in several tissue sections, including skin, liver, kidney, and spleen. Taken together, current data demonstrated that A. taiwanensis could suppress cellular senescence in HDFs, and might be used for health care.

Electroacupuncture attenuates chronic fibromyalgia pain through the phosphorylated phosphoinositide 3-kinase signaling pathway in the mouse brain.

OBJECTIVES: Fibromyalgia (FM) is a central nervous system disorder characterized by widespread mechanical hyperalgesia due to unknown mechanisms. Several inflammatory mediators, such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor, are increased in the serum of FM patients. Although medications including pregabalin, duloxetine, and milnacipran are used to treat FM, the results are unsatisfying. In the present study we assessed whether electroacupuncture (EA) can reduce chronic FM pain and then proposed an underlying mechanism for this effect. MATERIALS AND METHODS: Chronic FM pain was induced in mice by dual acid saline injection lasting up to 4 weeks. RESULTS: Chronic FM pain was treated by EA manipulation, but not in the sham operated group. Phosphorylated phosphatidylinositol 3-kinase (pPI3K), protein kinase B, mechanistic target of rapamycin, and nuclear factor kappa-light-chain-enhancer of activated B cells were unaltered in the mouse dorsal root ganglion (DRG) and spinal cord (SC) after inducing FM and administering EA treatment. The pPI3K-associated nociceptive signaling pathway was increased in the thalamus of FM mice, but reversed by EA. Similar results were observed in the mouse somatosensory cortex. CONCLUSION: These data suggest that EA has a significant effect on a signaling pathway in brain areas of FM mice. These findings suggest the value of EA for clinical practice.

Comparison of complexity and spectral indices of skin-surface laser-doppler signals in patients with breast cancer receiving chemotherapy and Kuan-Sin-Yin.

This study tested the hypothesis that measuring and analyzing skin-surface blood flow dynamics can be used to noninvasively discriminate the different microcirculatory and physiological function states of breast-cancer patients with chemotherapy between receiving and not receiving Kuan-Sin-Yin (KSY) treatment. The 17 included patients were assigned randomly to 2 comparison groups: Group K (n = 10) received KSY treatment, while Group NK (n = 7) did not receive KSY treatment. Beat-to-beat, spectral, and approximate-entropy (ApEn) analyses were applied to the 20-minute laser-Doppler sequences. The self-reported quality of life and cancer-related symptoms of patients were also investigated. In posttests, Group NK had a significantly larger ApEn ratio than that in Group K, significantly smaller values of laser-Doppler-flowmetry variability indices, and a slightly higher relative energy contribution of the neural-related frequency band compared to those in the pretests. Almost all cancer-related symptoms showed improvements in Group K compared to in Group NK. The present findings indicated that the present analysis can be used to detect the significantly different responses in the laser-Doppler indices between taking and not taking KSY. The KSY effect was also noted to be accompanied with improvement of EORTC QLQ-C30 scores. These could lead to a rapid, inexpensive, and objective technique for enhancing clinical applications in quality-of-life monitoring of breast cancer therapy.

Differences in time-domain and spectral indexes of skin-surface laser-Doppler signals between controls and breast-cancer subjects.

BACKGROUND: There is an urgent need to improve the early diagnosis of breast cancer. OBJECTIVE: The present study applied spectral and beat-to-beat analyses to laser-Doppler (LDF) data sequences measured on the skin surface on the back of the right hands, with the aim of comparing the different peripheral microcirculatory-blood-flow (MBF) perfusion condition between breast-cancer and control subjects. METHODS: ECG and LDF signals were obtained simultaneously and noninvasively from 23 breast-cancer patients and 23 age-matched control subjects. Time-domain beat-to-beat indexes and their variability parameters were calculated. Spectral indexes were calculated using the Morlet wavelet transform. RESULTS: The beat-to-beat LDF pulse width and its variability were significantly smaller in cancer patients than in the controls. The energy contributions of endothelial-, neural-, and myogenic-related frequency bands were also significantly smaller in cancer patients. CONCLUSIONS: The present study has revealed significant differences in the beat-to-beat and spectral indexes of skin-surface-acquired LDF signals between control subjects and breast-cancer patients. This illustrates that LDF indexes may be useful for monitoring the changes in the MBF perfusion condition induced by breast cancer. Since the breast-cancer patients were at TNM stages 0- 2, the present findings may aid the development of indexes for detecting breast cancer.

Characteristics of spectral indexes of the blood pressure waveform in patients with breast cancer.

AIM: A tumor can induce abnormalities in vessel properties and the blood flow distribution. The aim of the present study was to determine if blood-pressure-waveform (BPW) harmonic indexes can be used to discriminate hemodynamic differences between healthy control subjects and patients with breast cancer. METHODS: Ten-minute bilateral radial BPW signals were obtained noninvasively in 23 breast-cancer patients and 23 healthy subjects. The amplitude proportion (Cn), phase angle (Pn), and harmonic variability (CVn) were calculated for harmonics 1 to 10 of the BPW. RESULTS: C1, C2, and P1 were significantly smaller and P7, P9, CV2, and CV3 were significantly larger in the control group than in the cancer group. CONCLUSION: The differences identified between the breast-cancer and control groups illustrate significant hemodynamic changes induced by breast cancer at stages 0-2. The BPW harmonic indexes investigated in this study may be useful for detecting these hemodynamic changes and thus improving the sensitivity of discriminating between healthy controls and patients with early-stage breast cancer.

Complexity Analysis of Beat-to-Beat Skin-Surface Laser-Doppler Flowmetry Signals in Stroke Patients.

OBJECTIVES: This study performed skin-surface LDF measurements and SampEn analysis with the aims of (i) capturing the temporal complexity of cerebral hemodynamics in stroke patients and (ii) discriminating stroke patients from healthy control subjects. We also investigated the response induced by AS in beat-to-beat SampEn indexes of LDF signals. METHODS: LDF signals were obtained at bilateral TaiYang acupoints in 52 stroke patients. Each assessment involved a 20-minute baseline recording, a 20-minute AS, and a subsequent 20-minute recording. The FDT, FRT, and PW were calculated for each pulse of the LDF signals, and then their SampEn values were calculated. RESULTS: The SampEn values of FRT were significantly larger in the stroke group (1.064 ± 0.052 and p = 0.013 at the stroke side; 1.059 ± 0.055 and p = 0.017 at the controlateral side) than in the control group (0.975 ± 0.120). On the stroke side, the SampEn of value of FRT was significantly decreased following AS (1.064 ± 0.052 to 1.008 ± 0.060; p = 0.027). CONCLUSION: Larger SampEn values of FRT can be partly attributed to the local regulatory activities that are present in the stroke subjects when facing the induced abnormal vascular conditions and blood flow perfusion resistance. The present findings could aid the development of a noninvasive monitoring technique that will enable discrimination of the different microcirculatory responses in stroke patients.

Differences in the beat-to-beat parameters of skin-surface pulsatile laser-Doppler waveforms between stroke and normal subjects.

Walking can help improve the recovery after stroke. The present study used skin-surface laser-Doppler flowmetry (LDF) measurements and beat-to-beat waveform analysis with the aim of discriminating the microcirculatory blood flow (MBF) characteristics in stroke subjects subdivided into two groups according to their walking ability. Five-minute LDF measurements were performed in the following groups: Group A (cannot walk independently; n = 17), Group B (can walk independently; n = 11), and Group C (healthy controls; n = 17). The pulse width (PW) and foot delay time (FDT) and their coefficients of variation (PWCV and FDTCV, respectively) were calculated for the beat-to-beat LDF waveform. The FDT in Group A and the blood-pressure-normalized PW in Group C were significantly longer than the corresponding values in the other groups, and PWCV and FDTCV were significantly larger in Group C than in Group A. To our knowledge this is the first study demonstrating the feasibility of using a beat-to-beat LDF waveform index to discriminate between stroke subjects with different walking abilities and between stroke and normal subjects. It provides a noninvasive and real-time method for discriminating MBF characteristics, and thus could aid the development of an index for the early detection of stroke or for evaluating the recovery condition in stroke patients.

Complexity analysis of the microcirculatory-blood-flow response following acupuncture stimulation.

Beat-to-beat cardiovascular variability analysis provides important information on the circulatory regulatory activities. Changes in the arterial pulse transmission or the opening condition of arteriolar openings might change the fluctuation pattern of the MBF supply, and thus change the complexity property therein. We performed complexity analysis of beat-to-beat laser Doppler flowmetry (LDF) signals to study the microcirculatory-blood-flow (MBF) response at the needled site (Hegu acupoint) following acupuncture stimulation (AS). LDF signals were measured in male healthy volunteers (n=29). Each experiment involved recording a 20-minute baseline-data sequence and two sets of effects data recorded 0-20 and 50-70min after stopping AS. Approximate-entropy (ApEn) analysis, which quantifies the unpredictability of fluctuations in a time series, was performed on each 20-minute beat-to-beat LDF data sequence. The present findings indicate that AS can not only improve the local blood supply but may also increase ApEn values and decrease MBF variability parameters. This was the first attempt to apply complexity analysis to LDF signals in order to elucidate microcirculatory responses following AS. The observed results are probably attributable to the contradictory effects on the MBF supply induced by AS, which might interfere with the microcirculatory regulatory activities so as to increase the complexity of LDF signals. The present findings could help to identify the mechanism underlying the effects of AS, might aid the development of an index for monitoring the induced microcirculatory regulatory responses, and thus provide an evidence-based connection between AS and modern physiology.

Effects of acupuncture on the harmonic components of the radial arterial blood-pressure waveform in stroke patients.

MOTIVATION: Stroke induces abnormal microcirculatory blood flow perfusion resistance in cerebral vascular beds, which may in turn alter the arterial pulse transmission. This study aimed to determine if the frequency-domain harmonic index for the blood-pressure waveform is useful in monitoring the microcirculatory blood flow perfusion response in cerebral vascular beds of stroke patients following acupuncture stimulation. METHODS: Bilateral radial arterial blood-pressure waveform and laser-Doppler flowmetry signals were obtained noninvasively before and after acupuncture in 17 stroke patients. The amplitude proportion (Cn) for all the acquired pulses and the coefficient of variance (CVn) for harmonics 1-10 were calculated to evaluate the blood-pressure harmonic variability. RESULTS: The laser-Doppler flowmetry parameters showed that the cerebral microvascular blood flow supply could be improved following acupuncture. For the blood pressure waveform harmonic index, there were significant increases in C5 and C6 and decreases in CV5 and CV7 on the stroke-affected side, but no significant changes on the contralateral side. CONCLUSION: Cn values might reflect changes in arterial pulse transmission, and the blood-pressure-harmonic-variability response might be partly attributable to cardiovascular regulatory activities caused by acupuncture-induced changes in the cerebral microvascular blood flow perfusion. The present findings of blood pressure waveform harmonic analysis may be useful to the development of a noninvasive and real-time technique for evaluating treatment efficacy in stroke patients.

Acute microcirculatory responses induced by skin-surface vibration stimulation at a frequency near the heart rate.

OBJECTIVE: We aimed to elucidate the frequency-specific microcirculatory blood-flow (MBF) effect induced by weak vibration stimulation (VS) in healthy human subjects. METHODS: VS was implemented by a rod (connected to a DC motor) hitting a water-filled bag. VS was applied to the left palm at frequencies near to the heart rate (HR) (n=35; Group A) and 50% higher than the HR (n=20; Group B), and laser-Doppler-flowmetry measurements were made on the back of the left hand (Site 1). A control group without applying VS was also used (n=21). RESULTS: The mean MBF (MMBF), pulsatile MBF, and pulse width at Site 1 only increased significantly in Group A, and the coefficient of variance of the MMBF sequence increased significantly at Site 1 in Groups A and B. CONCLUSION: These results illustrate the VS-induced changes in the regulatory activities of arteriolar openings, and improvement of the MBF near the VS application site in Group A. The improvement in MBF depended on whether the VS frequency was near to, or higher than the HR. The present findings may be pertinent to amelioration of disease induced by an abnormal MBF.

Using a blood pressure harmonic variability index to monitor the cerebral blood flow condition in stroke patients.

OBJECTIVE: Beat-to-beat cardiovascular variability analysis provides important information on the autonomic control. Bilateral radial arterial blood pressure waveforms (BPW) in stroke patients were compared to explore the efficacy of frequency-domain variability index in evaluating bilateral differences in the cerebral blood-flow condition. METHODS: Five-minute BPW signals were obtained in 22 stroke patients (Group S) and 21 healthy volunteers (control Group C). Amplitude proportions of the acquired pulses and their coefficient of variance (CVn) were calculated for 1st-10th harmonics to evaluate the blood pressure harmonic variability (BPHV). RESULTS: In Group S, CV1-CV7 were significantly larger on the stroke side than on the contralateral side. CV1, CV3-CV5 and CV7 were significantly larger on the stroke side in Group S than on either side in Group C. CONCLUSIONS: We first demonstrate the feasibility of using BPHV index to noninvasively detect the bilateral difference in cerebral vascular resistance in stroke patients. Two main indexes could be developed based on the present results: (1) bilateral differences in BPHV in stroke patients; (2) BPHV differences between normal and stroke subjects. It might have meaning in developing an easy-to-perform, noninvasive and continuous monitoring technique to improve the early detection and disease progress monitoring for stroke.

Acupuncture stimulation causes bilaterally different microcirculatory effects in stroke patients.

The aim of this study was to determine the effects of acupuncture stimulation (AS) in stroke patients by analyzing the pulsatile waveform and frequency content of skin blood-flow signals recorded simultaneously on the bilateral skin surface of the head. Laser Doppler flowmetry (LDF) signals were obtained in 18 stroke patients. Each assessment involved a 20-min baseline recording, a 20-min AS, and a further 20-min recording. Significant bilateral differences in LDF parameters were noted following AS, with an increased pulsatile component of the microcirculatory blood flow (MBF), decreased blood-flow resistance, and decreased MBF variability in the vascular beds on the stroke-affected side. Spectral analysis revealed that the vasodilation on the stroke-affected side could be partly attributed to decreased sympathetic neural activity. This is the first study to demonstrate the feasibility of evaluating the cerebral MBF conditions induced by AS in stroke patients by noninvasive LDF measurement. The present skull-intact measurement setup could aid the development of noninvasive detection techniques for determining bilateral differences in the cerebral MBF, and could thus become useful for the efficacy evaluation of treatment techniques for stroke. It might also promote understanding of the mechanisms underlying the responses and possible treatment efficacy of AS as applied to stroke patients.

Earthworm extracts facilitate PC12 cell differentiation and promote axonal sprouting in peripheral nerve injury.

The present study provides in vitro and in vivo evaluations of earthworm (Pheretima aspergilum) on peripheral nerve regeneration. In the in vitro study, we found the earthworm (EW) water extracts caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as the expressions of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with EW extracts were used to bridge a 10 mm sciatic nerve defect in rats. Eight weeks after implantation, the group receiving EW extracts had a much higher success percentage of regeneration (90%) compared to the control (60%) receiving the saline. In addition, quantitative histology of the successfully regenerated nerves revealed that myelinated axons in EW group at 31.25 microg/ml was significantly more than those in the controls (p < 0.05). These results showed that EW extracts can be a potential growth-promoting factor on regenerating peripheral nerves.