Coaxial radiography guided puncture technique for percutaneous transforaminal endoscopic lumbar discectomy: A randomized control trial.

BACKGROUND: The coaxial radiography-guided puncture technique (CR-PT) is a novel technique for endoscopic lumbar discectomy. As the X-ray beam and the puncturing needle are maintained in a parallel and coaxial direction, the X-ray beam can be used to guide the trajectory angle, facilitating the choice of the puncture site and providing real-time guidance. This puncture technique offers numerous advantages over the conventional anterior-posterior and lateral radiography-guided puncture technique (AP-PT), especially in cases of herniated lumbar discs with a hypertrophied transverse process or articular process, high iliac crest, and narrowed intervertebral foramen. AIM: To confirm whether CR-PT is a superior approach to percutaneous transforaminal endoscopic lumbar discectomy compared to AP-PT. METHODS: In this parallel, controlled, randomized clinical trial, herniated lumbar disc patients appointed to receive percutaneous endoscopic lumbar discectomy treatment were recruited from the Pain Management Department of the Affiliated Hospital of Xuzhou Medical University and Nantong Hospital of Traditional Chinese Medicine. Sixty-five participants were enrolled and divided into either a CR-PT group or an AP-PT group. The CR-PT group underwent CR-PT, and the AP-PT group underwent AP-PT. The number of fluoroscopies during puncturing, puncture duration (min), surgery duration (min), VAS score during puncturing, and puncture success rate were recorded. RESULTS: Sixty-five participants were included, with 31 participants in the CR-PT group and 34 in the AP-PT group. One participant in the AP-PT group dropped out due to unsuccessful puncturing. The number of fluoroscopies [median (P25, P75)] was 12 (11, 14) in the CR-PT group vs 16 (12, 23) in the AP-PT group, while the puncture duration (mean ± SD) was 20.42 ± 5.78 vs 25.06 ± 5.46, respectively. The VAS score was 3 (2, 4) in the CR-PT group vs 3 (3, 4) in the AP-PT group. Further subgroup analysis was performed, considering only the participants with L5/S1 segment herniation: 9 patients underwent CR-PT, and 9 underwent AP-PT. The number of fluoroscopies was 11.56 ± 0.88 vs 25.22 ± 5.33; the puncture duration was 13.89 ± 1.45 vs 28.89 ± 3.76; the surgery duration was 105 (99.5, 120) vs 149 (125, 157.5); and the VAS score was 2.11 ± 0.93 vs 3.89 ± 0.6, respectively. All the above outcomes demonstrated statistical significance (P < 0.05), favoring the CR-PT treatment. CONCLUSION: CR-PT is a novel and effective technique. As opposed to conventional AP-PT, this technique significantly improves puncture accuracy, shortens puncture time and operation time, and reduces pain intensity during puncturing.

[Analysis of acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack based on complex network].

Acupoint-symptom relationship in CHENG Dan-an's Note About Treatise on Cold-Attack was analyzed based on complex network, acupoint names and indications were extracted from the book, which provided ideas and methods for promoting the modernization of acupuncture and moxibustion by using complex network technology. A total of 112 acupoints in 201 acupuncture prescriptions were included, and the total frequency of acupoints was 880 times, forming 42 034 acupoint pairs. In terms of network indexes, compared with the complex network of comprehensive acupuncture books, such as Meridian and Acupoint Science, Zhenjiu Dacheng, Acupuncture A and B Meridians formed based on the same mathematical method, the complex network model for CHENG Dan-an's Note About Treatise on Cold-Attack shows more typical small world effect, which is characterized by higher network density (6.762) and shorter average path length (1.064). This phenomenon may be related to the tongue and pulse which added the link between acupoints. For the node indexes, the analysis of topological indexes such as Page Rank shows that acupoints represented by Dazhui (GV 14) has higher compatibility value in the treatment of exogenous diseases, which further demonstrates the clinical value of eigenvector centrality in guiding intelligent compatibility of points.

Clinical Study of Acupotomy for Knee Osteoarthritis Based on the Meridian-Sinew Theory: A Randomized Controlled Clinical Trial.

This study was performed to compare the effectiveness of acupotomy based on the meridian-sinew theory with acupotomy based on the anatomical theory in the treatment of knee osteoarthritis (KOA). A total of 124 patients with knee osteoarthritis were randomized into the meridian-sinew (MS) group (63 patients) and anatomy group (61 patients). In the MS group, acupotomy based on the meridian-sinew theory was performed. In the anatomy group, acupotomy based on anatomy was applied. Patients were subgrouped by TCM Constitutions. The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index and visual analog scale (VAS) were used to evaluate treatment effectiveness. The results showed that VAS (F = 22.61, p < 0.01) and WOMAC (F = 24.84, p < 0.01) scores declined with time, and there was no significant difference between the two groups nor subgroups (Yang deficiency subgroup, Yin-Yang harmony subgroup, and the subgroup of the others). A total of 5 patients reported 6 cases of the minor adverse effect, and all patients achieved complete recovery without medical intervention. This study indicates that the effectiveness and safety of acupotomy based on the meridian-sinew theory are equivalent to that of acupotomy based on anatomy in KOA treatment.

Protective effects of berberine against MPTP-induced dopaminergic neuron injury through promoting autophagy in mice.

Berberine, an isoquinoline alkaloid isolated from Coptis chinensis, has been widely studied for its efficacy in the treatment of neurodegenerative diseases. However, the detailed mechanisms are unknown. In this study, the effects of berberine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of Parkinson's disease were investigated. We showed that treatment with berberine significantly ameliorates the degeneration of dopaminergic neurons in substantia nigra compacta (SNc) and improves motor impairment in MPTP-treated mice. Berberine also significantly decreased the level of α-synuclein and enhanced the microtubule-associated protein light chain 3 (LC3-II)-associated autophagy in the SN of MPTP-treated mice. Furthermore, adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) was activated by berberine. Berberine's actions were abolished by pre-treatment with 3-methyladenine (an autophagy inhibitor) or compound c (an AMPK inhibitor) in the MPP+-treated SH-SY5Y cells. These results suggested that the protective effects of berberine on the toxicity of MPTP could be attributed to berberine-enhanced autophagy via the AMPK dependent pathway.

Moxibustion against Cyclophosphamide-Induced Premature Ovarian Failure in Rats through Inhibiting NLRP3-/Caspase-1-/GSDMD-Dependent Pyroptosis.

Premature ovarian failure (POF) is a clinical term used to describe a condition in which women present with amenorrhoea, hypergonadotropic hypogonadism, and infertility under 40 years old, which are mainly characterized by ovarian granulosa cell inflammation and death. Pyroptosis is a proinflammatory form of programmed cell death. However, the roles of pyroptosis in POF and moxibustion (Mox) on pyroptosis in POF have not been elucidated. The aim of the present study was to investigate the protective effect of moxibustion against cyclophosphamide- (CP-) induced POF and to determine the underlying mechanisms. The results indicated that Mox could decrease the follicle-stimulating hormone (FSH) and luteotropic hormone (LH) and increase estradiol (E2) in serum, which indicated that it could improve ovarian reserve capacity. Mox also ameliorated CP-induced ovarian injury accompanied by decreased levels of interleukin-1ß (IL-1ß), IL-18, and gasdermin D (GSDMD), which are key features of pyroptosis. Further investigation showed that Mox alleviated POF through NLRP3-mediated pyroptosis. On the one hand, Mox directly inhibited TXNIP/NLRP3/caspase-1 signaling-induced pyroptosis, and on the other hand, it indirectly decreased NLRP3, pro-IL-1ß, and pro-IL-18 through inhibiting TLR4/MyD88/NF-κB signaling. Our results show that Mox might be a new therapeutic strategy for the treatment of POF.

The Effect of Sacral Neuromodulation in Ambulatory Spina Bifida Patients with Neurogenic Bladder and Bowel Dysfunction.

OBJECTIVE: To assess the effect of sacral neuromodulation (SNM) in ambulatory spina bifida patients with neurogenic bladder and bowel dysfunction. MATERIALS AND METHODS: We retrospectively reviewed the records of 29 ambulatory spina bifida patients with neurogenic bladder and bowel dysfunction who underwent SNM testing from July 2012 to January 2020. Clinical data and video-urodynamic parameters were collected and compared using the t-test and the chi-square test. The potential risk factors were considered by logistic regression analysis. P < .05 was considered significant. RESULTS: In the test phase, 21 patients (72.4%) achieved successful improvement of at least 1 symptom. The success rate for chronic urinary retention (26.09%) was significantly lower (P <.05) than that for urgency-frequency syndrome (58.82%) and urinary incontinence (56.25%). The mean neurogenic bowel dysfunction score decreased from 13.3±6.29 to 6.9±5.09 (P <.0001). The urodynamic evaluation showed a significant improvement in the mean maximum cystometric capacity, compliance, and maximum detrusor pressure (P <.05). Implantation was performed in 16 cases (55.17%). The analysis of the risk factors showed that chronic urinary retention was a statistically significant variable (P <.05). No complications were reported in the test phase. The average follow-up time was 41.19±33.06 months. Two patients changed to intermittent catheterization, and 2 patients changed to augmentation cystoplasty. CONCLUSION: SNM is effective for neurogenic bladder and bowel dysfunction in patients with ambulatory spina bifida, especially in those without chronic urinary retention. And SNM can also significantly improve the urodynamic parameters of these patients during the storage period.

Clinical study on electroacupuncture for obese patients with binge eating disorder: A retrospective study.

Binge eating disorder (BED) is a common dietary disorder among obese people. Obesity and eating disorders are related to mental health and physical health. At present, there is no definite and effective method for treatment in clinic. The curative effect of electroacupuncture on obesity is definite. Although there is no conclusive evidence to support its long-term benefits, electroacupuncture has been increasingly used in clinic. This retrospective study determined the prognosis and outcome of electro-acupuncture on obese patients with BED.One hundred forty-three patients with BED and obesity were found from 658 people who participated in the scientific experiment of obesity treatment in Nanjing Hospital of Traditional Chinese Medicine and Nanjing Brain Hospital from March 2015 to June 2018, and 84 patients (aged 18-40 years old) with valid data and uninterrupted treatment were found to be eligible for this retrospective study. According to the intervention methods, the patients were divided into electro-acupuncture combined with cognitive group (n = 32), cognitive therapy group (n = 28), and control group (n = 24). In this study, the 5th edition of Diagnosis and Statistics Manual of Mental Diseases, fasting blood glucose, fasting insulin, total cholesterol (TC), triglyceride, high-density lipoprotein, low-density lipoprotein, body fat rate, muscle mass, visceral index grade, nutrient intake (energy, protein, fat, carbohydrate), body weight, and weight changes before and after treatment were observed.Compared with the cognitive therapy group, negative emotion score, TC, triglyceride, high-density lipoprotein, waist circumference, BW, BMI, body fat percentage of the electroacupuncture combined with cognitive group were lower, while positive emotional scores were higher, and there were significant differences in negative emotional scores, TC, waist circumference and BMI (P < .05). The dietary energy and three major nutrients in the electroacupuncture combined with cognitive group were lower than those in the cognitive group and the blank group (P < .05).The current results suggest that electroacupuncture combined with cognitive therapy is more effective than cognitive therapy alone in treating obese patients with BED. Future prospective studies are necessary to further study the mechanism of electroacupuncture on the obese with BED.

Berberine alleviates rotenone-induced cytotoxicity by antioxidation and activation of PI3K/Akt signaling pathway in SH-SY5Y cells.

Berberine, an isoquinoline alkaloid isolated from traditional Chinese medicine, has been widely studied for its efficacy in the treatment of neurodegenerative diseases. However, berberine-mediated neuroprotection in the pathogenesis of Parkinson's disease is still uncertain. In this study, the effects of berberine on rotenone-induced neurotoxicity in SH-SY5Y cells were investigated. The results showed that berberine treatment significantly alleviated rotenone-induced decrease in the cell viability in SH-SY5Y cells. Further studies demonstrated that berberine suppressed the production of intracellular reactive oxygen species, restored the mitochondrial transmembrane potential, increased Bcl-2/Bax ratio, and decreased caspase-3 activation that induced by rotenone. Furthermore, berberine also restored the phosphorylation of Akt, which was downregulated by rotenone in SH-SY5Y cells. These results suggest that berberine protects rotenone-treated SH-SY5Y cells by antioxidation and activation of PI3K/Akt signaling pathway.

Targeting carbon nanotubes based on IGF-1R for photothermal therapy of orthotopic pancreatic cancer guided by optical imaging.

Pancreatic cancer is one of the most lethal malignancies worldwide. The existing therapeutic regimen in the clinic for advanced inoperable carcinomas are far from satisfactory, thus it is urgent to seek more effective anticancer strategies. In the pursuit of novel, more effective interventions, photothermal therapy (PTT) based on nanomaterials has attracted increased attention. Recent advances in related fields have catalyzed the generation of novel nanoprobes, such as organic dyes, metal nanoparticles. However, organic dyes are poorly stable and easy to quench while metal nanoparticles with potential metal toxicity are difficult to degrade, both of which have low light-to-heat conversion efficiency, broad spectrum of anti-tumor effects, and lack of tumor targeting specificity. Single-walled carbon nanotubes (SWNTs) can remedy the above inadequacies. Herein, we report our water-soluble, bio-stable and low-toxicity SWNTs with excellent photothermal conversion efficiency. Specific modifications can enable visualization of the aggregate characteristics of SWNTs at the macroscopic or microscopic level in tumors. The dye-conjugated SWNTs bound with targeting antibodies that can induce them specifically targeting to pancreatic tumors for purposes of performing dyes imaging-guided cytotoxic PTT. PTT using this method achieves precise and excellent curative effects with minimal adverse effects, thus providing a promising strategy for anticancer therapy.

Clinical characteristics and outcomes of traditional Chinese medicine-induced liver injury: a systematic review.

BACKGROUNDS: Traditional Chinese medicine (TCM) is becoming increasingly popular and related adverse events are often ignored or underestimated. AIMS: This systematic review aimed to evaluate the clinical characteristics and outcomes of TCM-induced liver injury (TCM-ILI) and to estimate the proportion of TCM-ILI in all drug-induced liver injuries (DILI). METHODS: China National Knowledge Infrastructure, Wanfang, VIP, PubMed, and Embase databases were searched. Demographic, clinical, and survival data were extracted and pooled. Factors associated with worse outcomes were calculated. For the proportion meta-analyses, the data were pooled by using a random-effects model. RESULTS: Overall, 21,027 articles were retrieved, of which 625 were finally included. There was a predominance of female and older patients. The proportion of liver transplantation was 2.18% (7/321). The mortality was 4.67% (15/321). Male, higher aspartate aminotransferase and direct bilirubin, and lower albumin were significantly associated with an increased risk of death/liver transplantation in TCM-ILI patients. The proportion of TCM-ILI in all DILI was 25.71%. The proportion was gradually increased with year. CONCLUSIONS: Our work summarises current knowledge regarding clinical presentation, disease course, and prognosis of TCM-ILI. TCM can result in hepatotoxicity, even death or necessitate life-saving liver transplantation. Governmental regulation of TCM products should be strictly established.

Clinical efficacy of intravesical electrical stimulation on detrusor underactivity: 8 Years of experience from a single center.

The aim of this study was to retrospectively evaluate the effectiveness of intravesical electrical stimulation (IVES) on detrusor underactivity (DU).From 2009 to 2016, a total of 105 patients with symptoms of DU who were treated with IVES were included in this retrospective study. The medical records, physical examination findings, urine culture results, and video-urodynamic studies were reviewed. Changes in post-void residual urine (PVR) and voiding efficiency (VE) were included for evaluation of efficacy. Patients achieving a >50% reduction in the PVR were regarded as responders. A >80% reduction in the PVR was considered obvious improvement. A questionnaire was administered to patients with bladder sensation.Of the 105 patients, the information of residual urine volume and voiding volume was obtained in 89 patients, and detailed pre- and post-IVES bladder sensation information was available on 96 patients. Of the 89 patients, 47.2% (42/89) were responders and achieved a >50% reduction in the PVR. Obvious improvement in the PVR, defined as a >80% reduction, occurred in 27% (24/89) of the patients. VE developed in 76.4% (68/89) of the patients, and 30.3% (27/89) of the patients increased >50%. Significant improvements in the PVR and VE were observed during IVES treatment (P < .05). Based on the questionnaire, bladder sensation developed and was sustained in 44.8% (43/96) of the patients.IVES provides a promising method for improving the PVR and VE in a majority of patients with DU. Thus, IVES is worth to further study and carry out.

Combination of sacral nerve and tibial nerve stimulation for treatment of bladder overactivity in pigs.

PURPOSE: Sacral nerve and tibial nerve stimulation have been singly used to treat overactive bladder (OAB). This study evaluated the effects of both combined stimulation on treating bladder overactivity in pigs and explored a novel treatment modality for OAB. METHODS: An implant-driven stimulator of the S3 spinal nerve was implanted in 5 pigs. The contralateral tibial nerve was stimulated by an external stimulator. Multiple cystometrograms were performed to determine the effects of single nerve stimulation and combination sacral nerve stimulation (SNS) and tibial nerve stimulation (TNS) on the micturition reflex by infusing normal saline (NS) or acetic acid (AA). RESULTS: AA-induced bladder overactivity significantly reduced bladder capacity (BC) to 16.3 ± 2.2% of the NS control level (389.4 ± 27.68 ml; P < 0.01). When given a single stimulation, both SNS and TNS significantly increased the BC to 39.2 ± 1.6% and 34.9 ± 5.0% of the NS control level (P < 0.01), respectively. Combined SNS and TNS significantly increased the BC to 50.2 ± 5.2% of the NS control level (P < 0.01) and induced a superior inhibitory effect than SNS or TNS alone (P < 0.05). CONCLUSIONS: Combination SNS and TNS induced a superior inhibitory effect on bladder overactivity in pigs compared to single stimulation and thus could be a novel treatment modality for OAB.

Involvement of opioid receptors in inhibition of bladder overactivity induced by sacral neuromodulation in pigs: A possible action mechanism.

AIMS: To determine the role of opioid receptors in the inhibition of bladder overactivity by sacral neuromodulation (SNM) in pigs, and explore the possible mechanism of SNM. METHODS: Both implant-driven stimulators of the S3 spinal nerve were implanted in seven pigs. Naloxone and tramadol were administered. Multiple cystometrograms were performed to determine the effects of SNM and opioid receptors on the micturition reflex by infusing normal saline (NS) or acetic acid (AA). RESULTS: AA-induced bladder overactivity significantly reduced the bladder capacity (BC) to 29.9 ± 3.9% of the NS control level (413.1 ± 55.4 mL) (P < 0.01). SNM significantly increased the BC to 39.4 ± 5.5% of the NS control level (P < 0.03). In the absence of SNM, the cumulative dose of naloxone (0.02 and 0.2 mg/kg intravenously) did not significantly change the BC (25.1 ± 3.1% and 20.2 ± 3.1% of the NS control level, respectively) (P > 0.05). In the presence of SNM, both doses of naloxone significantly reduced the BC to 27.2 ± 3.0% and 25.1 ± 2.9% of the NS control level (P < 0.05), respectively. In the absence of SNM, tramadol did not significantly change the BC (31.5 ± 3.9% of the NS control level) (P > 0.05). In the presence of SNM, tramadol significantly increased the BC to 49.1 ± 6.1% of the NS control level (P < 0.01). CONCLUSIONS: Opioid receptors play a role in inhibition of bladder overactivity during SNM. Combining SNM with tramadol could be a novel treatment modality for overactive bladder.

[Release Characteristics of Mercury from Submersed Typical Herbaceous Plants in the Water-Level Fluctuation Zone of the Three Gorges Reservoir Area].

In suit inundation experiments of three typical herbaceous plants were conducted in field to investigate the mercury release characteristics of plants grown in the water-level fluctuation zone of the Three Gorges Reservoir after flooding by regulating the water level. To realize this objective, this study mainly focused on the dynamic change of total mercury (THg) concentrations in plants after inundation, the release rate and flux of THg from plants and its release load in this region. The results showed that the release process of THg in plants fitted exponential curve, suggesting that mercury release rate was quick in the initial inundation period and then flat afterwards as the decomposing plants. The THg release amounts (followed the order of Alternanthera philoxeroides > Polygonum lapathifolium > Cynodon dactylon) were probably influenced by initial C/N ratio and THg concentrations of plants. The decrement of THg concentrations in per unit mass of plants residue was found to be generally proportional to their initial C/N ratio, while the THg release amounts were generally proportional to the initial THg concentrations of plants. The total release loads of three plants (Alternanthera philoxeroides, Polygonum lapathifolium, Cynodon dactylon) were estimated to be 167.31, 78.13 and 88.33 mg·hm-2, respectively, according to their weight distribution and biomass in the water-level fluctuation zone of the Three Gorges Reservoir Area.

[Effect of Low Molecular Weight Organic Acids on the Chemical Speciation and Activity of Mercury in the Soils of the Water-Level-Fluctuating Zone of the Three Gorges Reservoir].

To investigate the effect of low molecular weight organic acids ( LMWOA) on the ability of migration and the species of mercury in the soil of the Water-Level-Fluctuating Zone of the Three Gorges Reservoir, citric acid, tartaric acid and oxalic acid were dded into the soil to conduct simulation experiments. The results showed that the percentage of exchangeable mercury increased with the increase of the concentration of citric acid, but the value declined slightly as the concentration of tartaric acid and oxalic acid increased. While all three acids elevated the bioavailability of mercury, which increased with the increase of the concentration of acids. Vhen the concentration of citric acid reached 15 mmol x L(-1), the activation effect was the best. But for oxalic acid and citric acid, 10 mmol x L(-1) was the optimal concentration. In general, the effect of three organic acids on the activation of mercury in the soil followed the trend of citric acid > tartaric acid > oxalic acid. In the soil supplemented with 15 mmol x L(-1) citric acid, the change of mercury pecies was more and more striking with the prolonged incubation, and the conversion did not stop until 14 d, at that time the stomach cid dissolved mercury increased obviously, which was mainly converted from elemental mercury.

Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathology.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI) studies have previously shown hypointense signal in the motor cortex on T(2)-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or definite ALS by El Escorial criteria and 19 healthy controls underwent 3T MRI. A 7T MRI scan was carried out on five ALS patients who had motor cortex hypointensity on the 3T FLAIR sequence and on three healthy controls. Postmortem 7T MRI of the brain was performed in one ALS patient and histological studies of the brains and spinal cords were obtained post-mortem in two patients. The motor cortex hypointensity on 3T FLAIR images was present in greater frequency in ALS patients. Increased hypointensity correlated with greater severity of upper motor neuron impairment. Analysis of 7T T(2)(*)-weighted gradient echo imaging localized the signal alteration to the deeper layers of the motor cortex in both ALS patients. Pathological studies showed increased iron accumulation in microglial cells in areas corresponding to the location of the signal changes on the 3T and 7T MRI of the motor cortex. These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia.

Mutant TRPV4-mediated toxicity is linked to increased constitutive function in axonal neuropathies.

Mutations in TRPV4 have been linked to three distinct axonal neuropathies. However, the pathogenic mechanism underlying these disorders remains unclear. Both gain and loss of calcium channel activity of the mutant TRPV4 have been suggested. Here, we show that the three previously reported TRPV4 mutant channels have a physiological localization and display an increased calcium channel activity, leading to increased cytotoxicity in three different cell types. Patch clamp experiments showed that cells expressing mutant TRPV4 have much larger whole-cell currents than those expressing the wild-type TRPV4 channel. Single channel recordings showed that the mutant channels have higher open probability, due to a modification of gating, and no change in single-channel conductance. These data support the hypothesis that a "gain of function" mechanism, possibly leading to increased intracellular calcium influx, underlies the pathogenesis of the TRPV4-linked axonal neuropathies, and may have immediate implications for designing rational therapies.

Calcitonin gene-related peptide-mediated antihypertensive and anti-platelet effects by rutaecarpine in spontaneously hypertensive rats.

We have previously reported that Chinese traditional medicine rutaecarpine (Rut) produced a sustained hypotensive effect in phenol-induced and two-kidney, one-clip hypertensive rats. The aims of this study are to determine whether Rut could exert antihypertensive and anti-platelet effects in spontaneously hypertensive rats (SHR) and the underlying mechanisms. In vivo, SHR were given Rut and the blood pressure was monitored. Blood was collected for the measurements of calcitonin gene-related peptide (CGRP), tissue factor (TF) concentration and activity, and platelet aggregation, and the dorsal root ganglia were saved for examining CGRP expression. In vitro, the effects of Rut and CGRP on platelet aggregation were measured, and the effect of CGRP on platelet-derived TF release was also determined. Rut exerted a sustained hypotensive effect in SHR concomitantly with the increased synthesis and release of CGRP. The treatment of Rut also showed an inhibitory effect on platelet aggregation concomitantly with the decreased TF activity and TF antigen level in plasma. Study in vitro showed an inhibitory effect of Rut on platelet aggregation in the presence of thoracic aorta, which was abolished by capsazepine or CGRP(8-37), an antagonist of vanilloid receptor or CGRP receptor. Exogenous CGRP was able to inhibit both platelet aggregation and the release of platelet-derived TF, which were abolished by CGRP(8-37). The results suggest that Rut exerts both antihypertensive and anti-platelet effects through stimulating the synthesis and release of CGRP in SHR, and CGRP-mediated anti-platelet effect is related to inhibiting the release of platelet-derived TF.

Aspirin protected against endothelial damage induced by LDL: role of endogenous NO synthase inhibitors in rats.

AIM: To study the protective effect of aspirin on damages of the endothelium induced by low-density lipoprotein (LDL), and whether the protective effect of aspirin is related to reduction of nitric oxide synthase inhibitor level. METHODS: Vascular endothelial injury was induced by a single injection of native LDL (4 mg/kg) in rats. Vasodilator responses to acetylcholine (ACh) in the isolated aortic rings were determined, and serum concentrations of asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-alpha), and the activity of dimethylaminohydrolase (DDAH) were measured. RESULTS: A single injection of LDL (4 mg/kg) significantly decreased vasodilator responses to ACh, increased the serum level of ADMA, MDA, and TNF-alpha, and decreased DDAH activity. Aspirin (30 or 100 mg/kg) markedly reduced the inhibition of vasodilator responses to ACh by LDL, and the protective effect of aspirin at the lower dose was greater compared with high-dose aspirin group. Aspirin inhibited the increased level of MDA and TNF-alpha induced by LDL. Aspirin at the dose of 30 mg/kg, but not at higher dose (100 mg/kg), significantly reduced the concentration of ADMA and increased the activity of DDAH. CONCLUSION: Aspirin at the lower dose (30 mg/kg) protects the endothelium against damages elicited by LDL in vivo, and the protective effect of aspirin on endothelium is related to reduction of ADMA concentration by increasing DDAH activity.

The protective effects of ligustrazine on ischemia-reperfusion and DPPH free radical-induced myocardial injury in isolated rat hearts.

Previous investigations have suggested that tumor necrosis factor-alpha (TNF-alpha) can contribute to myocardial damage during ischemia-reperfusion. In the present study, we examined whether the cardioprotective effects of ligustrazine are related to inhibition of TNF-alpha production in the rat models of ischemia-reperfusion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-induced myocardial injury. Ischemia for 20 min and reperfusion for 40 min caused a decline in cardiac function (left ventricular pressure, +/- d p/d t(max), heart rate and coronary flow) and an increase in the release of creatine kinase in coronary effluent and the content of TNF-alpha in myocardial tissues. Similarly, perfusion with DPPH (100 nM) for 30 min significantly decreased cardiac function, and increased the release of creatine kinase and the content of TNF-alpha. Ligustrazine at the concentration of 40 or 80 mg/L markedly improved cardiac function and reduced the release of creatine kinase and the content of TNF-alpha in myocardial tissues in hearts subjected to ischemia-reperfusion or DPPH perfusion. These results suggest that the cardioprotection afforded by ligustrazine is related to a reduction of TNF-alpha content by inhibition of free radical production in isolated rat hearts.