Effect of electroacupuncture on rats with chronic constriction injury-induced neuropathic pain.

We adopt the chronic constriction injury (CCI) model to induce neuropathic pain to Spragrue-Dawley (SD) rats by ligating the right sciatic nerve of using four 4-0 chromic gut sutures and subsequently applying 2 and 15 Hz electroacupuncture (EA), respectively, to the right (ipsilateral) Zusanli (St-36) and Shangjuxu (St-37) acupoints. The results of this study are summarized as follows: (1) the differences in withdrawal latencies for the radiant heat test and total lift leg counts for the cold plate test (4°C) of the control (i.e., non-EA) and sham groups were greater than those of the 2 Hz EA (2EA) and 15 Hz EA (15EA) groups; (2) the von Frey test filament gram counts of the control and sham groups were less than those of the 2EA and 15EA groups on the 6th, 7th, 8th, 11th, 12th, and 13th day following ligation; and (3) the 2EA and 15EA groups exhibited reduced cerebral transient receptor potential vanilloid type 4 (TRPV4) expressions, although we did not observe a similar effect for cerebral TRPV1 or spinal TRPV4/TRPV1 expressions. These findings show that 2 and 15 Hz EA can reduce CCI-induced neuropathic pain, which indicates that various spinal segmental and gate effects have a crucial function in pain reduction. The relationship between EA and TRPV4/TRPV1 expression requires further study.

Neuroprotective Effect of Uncaria rhynchophylla in Kainic Acid-Induced Epileptic Seizures by Modulating Hippocampal Mossy Fiber Sprouting, Neuron Survival, Astrocyte Proliferation, and S100B Expression.

Uncaria rhynchophylla (UR), which is a traditional Chinese medicine, has anticonvulsive effect in our previous studies, and the cellular mechanisms behind this are still little known. Because of this, we wanted to determine the importance of the role of UR on kainic acid- (KA-) induced epilepsy. Oral UR for 6 weeks can successfully attenuate the onset of epileptic seizure in animal tests. Hippocampal mossy fiber sprouting dramatically decreased, while neuronal survival increased with UR treatment in hippocampal CA1 and CA3 areas. Furthermore, oral UR for 6 weeks significantly attenuated the overexpression of astrocyte proliferation and S100B proteins but not γ-aminobutyric acid A (GABA(A)) receptors. These results indicate that oral UR for 6 weeks can successfully attenuate mossy fiber sprouting, astrocyte proliferation, and S100B protein overexpression and increase neuronal survival in KA-induced epileptic rat hippocampus.

Interleukin-1beta mediates sleep alteration in rats with rotenone-induced parkinsonism.

STUDY OBJECTIVE: Recently, the pathogenesis of Parkinson disease (PD) has been focused on microglial activation, especially the subsequent increase of cytokines. A body of clinical evidence suggests that sleep is altered in patients with PD; however, there is a lack of understanding of the basic cellular mechanism. This study was designed to elucidate the influence of brain interleukin (IL)-1beta on sleep changes, in addition to the dopaminergic and gamma-aminobutyric acid (GABA)-ergic systems, in an animal PD model. DESIGN: We employed a long-term subcutaneous infusion of rotenone, a mitochondrial complex-I inhibitor, to induce a parkinsonism-like model in rats. Behavioral tests and tyrosine hydroxylase immunocytochemistry were used for confirmation of PD in this animal model. Pharmacologic agonist and antagonists were administered centrally to test the involvement of dopamine, GABA, and IL-1 in rotenone-induced sleep alteration. Protein expression of cytokines, ie, IL-1beta and tumor necrosis factor alpha (TNF-alpha), in 5 distinct brain regions was also determined by Western blot and enzyme-linked immunosorbent assay (ELISA). SETTING: Sleep-recording equipment in the National Taiwan University and China Medical University. PARTICIPANT AND INTERVENTIONS: Male Sprague-Dawley rats were implanted with electroencephalogram electrodes, a thermistor, and an intracerebroventricular guide cannula. Chronic infusion of rotenone was given by an Alzet minipump implanted subcutaneously on the back of each rat. MEASUREMENT AND RESULTS: We found that locomotion activity was reduced, slow-wave sleep (SWS) was increased during the dark (active) phase and decreased during the light (rest) period, and rapid eye movement sleep (REM) was enhanced in the dark period after rotenone treatment. This rotenone PD animal model successfully causes loss of tyrosine hydroxylase-immunopositive neurons in the substantia nigra; induces the events of sleep disturbance, such as excessive daytime sleepiness and insomnia during the nighttime, that are seen in patients with PD; and suppresses locomotion. Our results that intracerebroventricular administration of dopamine and blockade of GABA in the brain have less significant effect on rotenone-induced sleep alteration suggest that the sleep disturbance is not primarily mediated by the disruption of dopaminergic and GABAergic systems in the current PD rat model. The expression of TNF-alpha was not altered by rotenone. However, the results of enhanced expression of IL-1beta in the hypothalamus after rotenone and that of the blockade of sleep alteration, but not the locomotion activity, by intracerebroventricular administration of an IL-1 receptor antagonist implies that increased IL-1beta in the hypothalamus mediates sleep alteration, but not the locomotion, in rats with rotenone-induced parkinsonism. CONCLUSION: These observations suggest that rotenone-induced sleep-wake alteration is dominated by central increase of somnogenic IL-1.

Design and biological activities of novel inhibitory peptides for SARS-CoV spike protein and angiotensin-converting enzyme 2 interaction.

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). The binding of SARS-CoV spike (S) protein to cellular angiotensin-converting enzyme 2 (ACE2) is the first step in SARS-CoV infection. Therefore, we assayed the inhibitory effects of small peptides derived from S protein on the binding of S protein to ACE2 and on the S-protein-pseudotyped retrovirus infectivity. SP-4 (residues 192-203), SP-8 (residues 483-494), and SP-10 (residues 668-679) significantly blocked the interaction between S protein and ACE2 by biotinylated enzyme-linked immunosorbent assay, with IC(50) values of 4.30 +/- 2.18, 6.99 +/- 0.71, and 1.88 +/- 0.52 nmol, respectively. Peptide scanning suggested the region spanning residues 660-683 might act as a receptor-binding domain. SP-10 blocked both binding of the S protein and infectivity of S protein-pseudotyped retrovirus to Vero E6 cells. In conclusion, this is the first report of small peptides designed to disrupt the binding of SARS-CoV S protein to ACE2. Our findings suggest that SP-10 may be developed as an anti-SARS-CoV agent for the treatment of SARS-CoV infection.

A clinical study of acupuncture and SSP (silver spike point) electro-therapy for dry eye syndrome.

The present study was designed as a clinical trial to assess the efficacy of acupuncture and silver spike point (SSP) electro-therapy on dry eye syndrome. A total of 43 dry eye syndrome patients participated in the present study. Subjects were divided into control, acupuncture and SSP electro-therapy groups. The three groups were all given artificial tears treatment. Patients in the treatment groups were given two 20-minute treatments of either acupuncture or SSP. Assessment was carried out using the Basal Schirmer test, tear break-up time (BUT), visual analog scale (VAS) and an overall score of eye condition. After four weeks of treatment, both the acupuncture and SSP treatment groups showed improvements over the control group, in Schirmer tests of the left eye and average tearing of both eyes. After 8 weeks of treatment, both treatment groups showed improvements over the control group both in Schirmer tests and VAS. For the right eye, treatment groups showed significant improvements in Schirmer test and VAS versus the control group averages for both eyes. There was no significant difference in BUT at any time. Comparing scores before and after treatment, the acupuncture and SSP groups showed a significant improvement compared to the control group. The acupuncture group showed a greater 8-week improvement in Schirmer tests scores compared to the SSP group. However, the SSP group patients used fewer applications of artificial tears. Acupuncture and SSP electro-therapy were effective in increasing tear secretion in patients with dry eye syndrome. The SSP electro-therapy not only alleviated dry eye syndrome, but also reduced the number of applications of artificial tears necessary.

Activation of activator protein-1 in cells exposed to electrical stimulation of various parameters used in electroacupuncture therapy.

The aim of this study was to investigate the effect of electrical stimulation on activator protein-1 (AP-1) in recombinant liver cells. In order to elucidate the molecular effects of electrical stimulation on cells, AP-1 expression was detected by a luciferase assay. The parameters used were taken from clinical electroacupuncture (EA) therapy as follows: biphasic rectangular symmetrical pulses (frequency: 2, 10 and 100 Hz; pulse width: 50, 80, 130 and 250 microsec; intensity: 1, 2, 5 and 10 mA; time: 5, 10, 20 and 30 minutes). S (10% fetal bovine serum in medium), SF (serum free medium) and 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment represented the experimental, negative and positive groups, respectively. We found that electrical stimulation with 10 Hz, a pulse width of 130 microsec, and a duration of 30 minutes gave a significant increase in AP-1 activity. In contrast, the intensity of the stimulation had no significant effect on AP-1 activity. In conclusion, our data suggest that electrical stimulation with an appropriate frequency, duration and pulse width could cause an increase in AP-1 activity in cells.

Electroacupuncture at ST36-ST37 and at ear ameliorates hippocampal mossy fiber sprouting in kainic acid-induced epileptic seizure rats.

Our previous study showed that mossy fiber sprouting can occur in the hippocampus region in rats 6 wk after kainic acid-induced epileptic seizure, and this mossy fiber sprouting can facilitate epileptogenesis. Transcutaneous auricular vagal nerve stimulation (VNS), which is similar to cervical VNS, can reduce the occurrence of epileptic seizure in intractable epilepsy patients. Greater parasympathetic nerve activity can be caused by 2 Hz electroacupuncture (EA). Therefore, we investigated the effect of 2 Hz EA at ST-36-ST37 and at the ear on mossy fiber sprouting in kainic-treated Sprague-Dawley rats. The results indicated that applying 2 Hz EA at ST36-ST37 and at the ear for 3 d per week over 6 consecutive weeks can ameliorate mossy fiber sprouting in the hippocampus region of rats. These results indicated that applying 2 Hz EA at ST36-ST37 and at the ear might be beneficial for the treatment and prevention of epilepsy in humans.

Effect of oral administration of Pheretima aspergillum (earthworm) in rats with cerebral infarction induced by middle-cerebral artery occlusion.

We investigated the curative effect of Pheretima aspergillum (earthworm, PA) on rats with middle cerebral artery occlusion (MCAo). The MCAo-induced cerebral infarction was established and its underlying mechanisms by counting the infarction areas and evaluating the rats' neurological status. Immunostaining was used to test the expression of NeuN, and glial fibrillary acidic (GFAP), S100B, and brain-derived neurotrophic factor (BDNF) proteins. Our results showed that oral administration of PA for two weeks to rats with MCAo successfully reduced cerebral infarction areas in the cortex and striatum, and also reduced scores of neurological deficit. The PA-treated MCAo rats showed greatly decreased neuronal death, glial proliferation, and S100B proteins in the penumbra area of the cortex and in the ischemic core area of the cortex, but BDNF did not changed. These results demonstrated novel and detailed cellular mechanisms underlying the neuroprotective effects of PA in MCAo rats.

2 Hz electro-acupuncture at yinlingquan (SP9) and ququan (LR8) acupoints induces changes in blood flow in the liver and spleen.

According to the principles of traditional Chinese medicine, channels and collaterals within the body provide pathways through which qi and blood travel, and each channel or collateral is linked with a specific organ. The Yinlingquan (spleen 9, SP9) and Ququan (liver 8, LR8) acupoints represent the sea points of the spleen and liver meridians, respectively, from which qi and blood flow into their specific visceral organs. The purpose of this study was to investigate the changes in blood flow/perfusion in the liver and spleen resulting from the application of 2 Hz electro-acupuncture (EA) to the Yinlingquan (SP9) or Ququan (LR8) acupoints. A total of 18 Spragrue-Dawley rats were randomly divided into three groups of six rats each as follows: sham group receiving sham EA; Yinlingquan (SP9) group receiving 2 Hz EA, applied at bilateral Yinlingquan (SP9) acupoints; and Ququan (LR8) groups receiving 2 Hz EA, applied at bilateral Ququan (LR8) acupoints. The mean blood flow/perfusion of the spleen and liver was recorded using a laser Doppler blood flow monitor prior to EA (representing the baseline), during EA, and post-EA. Each measurement period lasted ten minutes. Nitric oxide levels were also measured from the right femoral arterial blood, following the conclusion of each series of blood flow/perfusion recordings. The results indicate that the sham EA did not increase the mean blood flow/perfusion in the liver or spleen; 2 Hz EA at bilateral Yinlingquan (SP9) acupoints increased the mean blood flow/perfusion in the spleen, but not in the liver. In contrast, 2 Hz EA at bilateral Ququan (LR8) acupoints increased the mean blood flow/perfusion in the liver, but not in the spleen. Nitric oxide levels showed no significant difference between any of the groups at any stage of the measurements. According to the results, we conclude that EA at the Yinlingquan (SP9) and Ququan (LR8) acupoints can increase the blood flow in the spleen and liver, respectively.

Chinese medicine patterns in patients with post-stroke dementia.

UNLABELLED: A stroke often results in post-stroke dementia, a rapid decline in memory and intelligence causing dysfunctions in daily life. The Chinese medicine doctor uses 4 examinations of inspection, listening, smelling, and feeling to determine the Chinese medicine pattern (CMP). Therefore, the purpose of the present study was to investigate the CMP in patients with post-stroke dementia. A total of 101 stroke patients were examined, consistent with the DSM IV diagnostic criteria of the American Psychiatric Association, as well as the National Institute of Neurological Disorders and Stroke-Association International pour Ia Recherche et I'Enseignement en Neurosciences vascular dementia diagnostic criteria of post-stroke dementia. RESULTS: 100 patients (99.0%) were KEDP (kidney essence deficiency pattern, shèn jing kui xu zhèng, ), 83 patients were AHLYP (ascendant hyperactivity of liver yang pattern, gan yáng shàng kàng zhèng, ), 83 patients were QBDP (qi-blood deficiency pattern, qì xuè kui xu zhèng, ), 81 patients were SBOCP (static blood obstructing the collaterals pattern, yu xuè zǔ luò zhèng, ), 72 patients were BSTRP (bowels stagnation turbidity retention pattern, fǔ zhì zhuó liú zhèng, ), 50 patients were FHIEP (fire heat interior excess pattern, huǒ rè nèi sheng zhèng, ), and 39 participants (38.6%) were PTOOP (phlegm turbidity obstructing the orifices pattern, tán zhuó zǔ qiào zhèng, ); one to 31 patients have at least 2 CMPs simultaneously. In conclusion, the most CMP is KEDP CMP in the post-stroke dementia patients, and one patient may have one or at least 2 CMPs simultaneously.

The 2 Hz and 15 Hz electroacupuncture induced reverse effect on autonomic function in healthy adult using a heart rate variability analysis.

The purpose of the present study was to investigate effect of electro-acupuncture (EA) at different frequencies on autonomic function. Twenty healthy adult volunteers were studied, and underwent 4 sessions of EA (sham, 2 Hz, 15 Hz, and 50 Hz). Sham, 2 Hz, 15 Hz, and 50 Hz EA was applied to the bilateral Leg Three Li ( zú san lǐ, ST-36) and Upper Great Hollow ( shàng jù xu, ST-37) acupoints. The intensity of electrical stimulation was adjusted to obtain visible twitching of the anterior tibial muscle about 2.0-2.5 mA except sham without electrical stimulation. The components of heart rate variability (HRV) and blood pressure were measured before EA (BLP), EA (EAP), and post-EA periods (PEP). The results indicated that the natural logarithmic high frequency power (lnHF) of HRV was greater during PEP than during the BLP in the 2 Hz EA sessions. The natural logarithmic low frequency power (lnLF) of HRV was greater during the PEP than during the BLP in 15 Hz EA sessions, suggesting that 2 Hz EA apply to Leg Three Li ( zú san lǐ, ST-36) and Upper Great Hollow ( shàng jù xu, ST-37) acupoints increased vagal activity, whereas 15 Hz EA increased sympathetic activity.

Chinese medicine acupoint herbal patching for allergic rhinitis: a randomized controlled clinical trial.

The aim of this study is pursue the effect of herbal point-patch treatment on allergic rhinitis patients by investigation of the changes of serum total IgE (T-IgE) and eosinophile cationic protein (ECP) levels and through assessment of the results of SF-36 and rhinitis severity questionnaires. A prospective, randomized, single-blind, parallel, controlled study was used. Forty- three eligible participants were selected from outpatients of the Dept. of Ear, Nose, and Throat and Chinese medicine clinic, and 33 eligible participants completed the treatment satisfactorily. Participants used a Chinese herbal point-patch or a placebo patch once a week, for three hours at a time, after being randomly assigned to a control or an experimental group. Each treatment course was three weeks in duration, and each participant underwent two courses of treatment. Before and after each course, participants evaluated the effectiveness of the treatment by completing a questionnaire, and blood samples were collected for T-IgE and ECP analysis. The data revealed that the acupoint herbal patch is a valuable treatment for allergic rhinitis, especially in the symptoms of sneezing, running and itchy nose. The results of the SF-36 indicate a distinct improvement in GH (general health) and VT (vitality) in patients treated with acupoint herbal patches. This study supports the belief that the acupoint herbal patch is an effective treatment for allergic rhinitis and can significantly improve general health, social life and vitality in quality of life.

Effects of electroacupuncture at 'Anmian (Extra)' acupoints on sleep activities in rats: the implication of the caud al nucleus tractus solitarius.

Electroacupuncture (EAc) possesses a broad therapeutic effect, including improvement of sleep disturbances. The mechanism of sleep improvement with EAc, however, is still unclear. The present study investigated the effects of EAc stimulation of 'Anmian (extra)' acupoints on sleep organization and the implication of an active structure, the caudal nucleus tractus solitarius (NTS). Rats were implanted with electroencephalogram (EEG) recording electrodes, and 32-gauge acupuncture needles were bilaterally inserted into 'Anmian (extra)' acupoints in the rats, followed by electrical stimulation for 20 min. Twenty-three-hour continuous EEGs were then recorded. Results showed that rapid eye movement sleep (REMS) was enhanced during the dark period when a single EAc stimulation was given 25 min prior to the onset of the dark period. REMS and slow-wave sleep (SWS) increased during the dark period after administration of EAc stimuli on 2 consecutive days. Electrical stimulation of non-acupoints produced no change in the sleep pattern. Pharmacological blockade of muscarinic cholinergic receptors by systemic administration of scopolamine dose-dependently attenuated EAc-induced changes in REMS and SWS. Furthermore, electrical lesions in the bilateral caudal NTS produced significant blockade of EAc-induced sleep enhancement. However, in rats without EAc, scopolamine increased SWS during the dark period, but caudal NTS lesions did not alter sleep. In addition, neither EAc nor scopolamine with EAc manipulation produced any change in the slow-wave activity (SWA) during SWS; however, the SWA during SWS was significantly reduced after caudal NTS lesion with EAc. These results suggest that the caudal NTS may be involved in the regulation of EAc-induced sleep alterations.