A novel method of sacral nerve stimulation for colonic inflammation.

BACKGROUND: Vagal nerve stimulation has been reported to treat inflammation with promising results. The aims of our study were to optimize sacral nerve stimulation (SNS) methodologies for colonic inflammation in a rodent model of colitis and to investigate autonomic and cytokine mechanisms. METHODS: Three major efforts were made in optimizing SNS: (a) to determine the best stimulation duration: SNS-0.5h daily, SNS-1h daily, and SNS-3h daily with the parameters set at 5 Hz, 10 seconds on, 90 seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5 Hz intermittent stimulation vs 14 Hz-210 µs continuous stimulation. Inflammatory responses were assessed by the disease activity index (DAI), histological analyses, and the myeloperoxidase (MPO) activity. Levels of inflammatory cytokines, norepinephrine (NE), and pancreatic polypeptide (PP) in both plasma and colon tissues were assessed. KEY RESULTS: Both SNS-1h and SNS-3h significantly ameliorated intestinal inflammation; SNS-1h was superior to SNS-3h. Bipolar but not bilateral or unipolar stimulation improved the inflammation in colitis. SNS with 5 Hz intermittent stimulation but not the 14 Hz continuous SNS was better for treating colitis in rats. SNS with the optimized stimulation parameters increased vagal activity and decreased sympathetic activity. CONCLUSION & INFERENCES: Bipolar stimulation for 1 hour daily using intermittent 5 Hz parameters is most effective in improving colonic inflammation in TNBS-treated rats by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the modulation of the autonomic function.

Sacral nerve stimulation prompts vagally-mediated amelioration of rodent colitis.

Neuromodulation based on the vagal anti-inflammatory reflex has emerged as an exciting therapeutic approach for chronic inflammatory diseases. However, it is unclear whether direct stimulation of the vagus or of pelvic nerves coming from sacral roots, providing the bulk of colonic parasympathetic innervation, is the best approach. We hypothesized that sacral nerve stimulation (SNS) would be an effective treatment for colitis. Age and sex-matched Sprague-Dawley rats were administered 5% dextran sulphate sodium (DSS) in drinking water ad libitum for 7 days. A group of rats was sacrificed after DSS treatment, and the remaining rats were randomized to either sham-SNS or SNS groups, which were performed for 1 hr daily for 10 days. Stimulations were delivered via chronically implanted electrodes using an 8-channel universal pulse generator. Sacral nerve stimulation promoted recovery of colitis demonstrated by decreased disease activity index, myeloperoxidase activity, tissue TNF-alpha, and histological scores as well as an increased colonic M2 macrophage population. Heart rate variability analysis demonstrated a decrease in low frequency and increase in high frequency with SNS, corresponding to increased vagal tone. Additionally, plasma pancreatic peptide was increased and norepinephrine was decreased after SNS in colitis while colon tissue acetylcholine was increased with SNS. This is the first study to the best of our knowledge that demonstrates the benefit of SNS with autonomic mediation. SNS alters the expression of inflammatory cytokines and macrophages as well as modulates neurotransmitters involved in systemic inflammation.

Home-Based Transcutaneous Neuromodulation Improved Constipation via Modulating Gastrointestinal Hormones and Bile Acids.

This study aims to investigate the role of transcutaneous neuromodulation (TN) on the regulation of gastrointestinal hormones and bile acids in patients with functional constipation (FC). Twenty FC patients were treated with TN for four weeks. The effects of TN on symptoms were evaluated by questionnaires. Plasma levels of serotonin (5-HT), motilin, somatostatin, and vasoactive intestinal peptide (VIP) were measured by ELISA and 12 individual bile acids assayed by liquid chromatography tandem mass spectrometry. Results were as follows. (1) TN treatment increased the frequency of spontaneous bowel movement, improved the Bristol Stool Score, and reduced Patient Assessment of Constipation Symptom score and Patient Assessment of Constipation Quality of Life score. (2) FC patients showed decreased plasma levels of 5-HT, motilin, and VIP and an increased plasma level of somatostatin (P < 0.05). Four-week TN treatment increased plasma levels of 5-HT and motilin and decreased the plasma level of somatostatin in the FC patients (P < 0.05). (3) Taurocholic deoxycholate, taurocholic acid, and taurocholic lithocholic acid were increased in the FC patients (P < 0.005) but reduced by TN treatment (P < 0.05). This study has suggested that the therapy may improve the symptoms of FC by alleviating the disorders of gastrointestinal hormones and bile acids.

[Determination of Total Sulfur Dioxide in Chinese Herbal Medicines via Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry].

As an important treatment method, sulfur fumigation plays an essential role in the production and preservation of traditional Chinese herbal medicines. Although there is strict regulation on the use of sulfur dioxide, the abuse of sulfur dioxide still occurred from time to time. And the public faces a high risk of exposure. Because of the poor precision and tedious preparation procedures of traditional recommended titration, the accurate and convenient determination of sulfur dioxide in Chinese herbal medicines is still a critical analytical task for medicines safety and the public health. In this study, an accurate, high-throughput, and convenient method for the absolute determination of SO2 in Chinese herbal medicines based on triple quadrupole inductively coupled plasma mass spectrometry (ICP-MS/MS) technique is developed. The study compared the quantitative ability for sulfur when the ICP-MS operated under traditional single quadrupole (QMS) mode and novel triple quadrupole (MS/MS) mode with three Reaction/Collision cell condition (no gas, helium, and oxygen). The result indicated that when the concentration of sulfate ranging from 0.5 to 100 mg · L⁻¹, isotopic ³4S can be selected as quantitative ion either the ICP-MS operated under the QMS mode or MS/MS mode. The use of helium in the Reaction/Collision cell decreased the single intensity of background ions. Better than QMS mode, the MS/MS mode can effectively reduced background interference. But there are no significant differences about the linear range and limit of detection. However, when the ICP-MS operated under MS/MS mode and oxygen was used as reaction gas in the Reaction/Collision cell, the ICP-MS/MS provided an interference-free performance, the linear range and limit of detection improved significantly. Either ³²S or ³4S exhibits an excellent linearity (r > 0.999) over the concentration range of 0.02-100 mg · L⁻¹, with a limit of detection of 5.48 and 9.76 µg · L⁻¹ for ³²S¹6O4²â» and ³4S¹6O4²â», respectively. The Chinese herbal medicines was treated using microwave digestion added 6 mL nitric acid and 2 mL hydrogen peroxide before analysis. The amount of nitric acid and hydrogen peroxide were optimized. The method was validated using Chinese herbal standard reference material GBW10020. The sample was treated and detected in six parallel, and the average concentrations obtained using the developed method (0.42% ± 0.01%) is in excellent agreement with the standard concentration (0.41%± 0.03%). The study demonstrates an accurate and convenient approach for the quantification of SO2 in Chinese herbal medicines.

Iron-Deficiency Anemia After Laparoscopic Roux-en-Y Gastric Bypass in Chinese Obese Patients with Type 2 Diabetes: a 2-Year Follow-Up Study.

BACKGROUND: This study was conducted to evaluate the prevalence of iron-deficiency anemia (IDA) after Roux-en-Y gastric bypass (RYGB) in Chinese obese patients with type 2 diabetes (T2DM). Furthermore, we evaluate potential predicting factors for onset of IDA after RYGB. METHODS: A total of 184 obese T2DM individuals who underwent RYGB were enrolled in the study. Patients were divided into three groups: male, premenopausal female, and postmenopausal female. Hematologic parameters were obtained prior to and after surgery on standardized time intervals up to 24 months postoperatively. RESULTS: At baseline, 6.0 % of patients were anemic, with similar percentages of anemic patients in each group. The relative decrease in the mean hemoglobin (Hb) level was significantly more pronounced for premenopausal female than for postmenopausal female or male. The percentage of anemia in male group had increased to 15.2 and 17.0 % at 6 and 12 months, respectively, and then decreased to 4.5 % at 24-month visit. In postmenopausal female group, the percentages of anemia constantly increase to 34.0 % at 6-month follow-up. Then, it decreased gradually to 25.0 and 26.7 % at 12- and 24-month visits, respectively. In premenopausal female group, the anemia percentages dramatically increased to 62.5 % at 24-month follow-up. Multiple logistic regression indicated that lower serum ferritin level preoperative and female were associated with higher possibility to suffer IDA 2 years after RYGB. CONCLUSIONS: Iron-deficiency and IDA are extremely frequent after RYGB in Chinese obese patients with T2DM. Premenopausal female presents unexpectedly high incidence of IDA during the 2-year observation.

Ameliorating effect of transcutaneous electroacupuncture on impaired gastric accommodation induced by cold meal in healthy subjects.

BACKGROUND: Impaired gastric accommodation is recognized as one of major pathophysiologies in functional dyspepsia and gastroparesis. Electroacupuncture has been shown to improve gastric accommodation in laboratory settings. It is, however, unknown whether it exerts similar ameliorating effect in humans and whether needleless transcutaneous electroacupuncture (TEA) is also effective in improving gastric accommodation. AIM: The aim was to investigate the effects of TEA on gastric accommodation, gastric slow waves, and dyspeptic related symptoms. METHODS: Thirteen healthy volunteers were studied in four randomized sessions: control, cold nutrient liquid, cold nutrient liquid + sham-TEA, and cold nutrient liquid + TEA. The subjects were requested to drink Ensure until reaching maximum satiety. The electrogastrogram (EGG) and electrocardiogram (ECG) were recorded to assess the gastric and autonomic functions respectively. RESULTS: 1) Gastric accommodation was reduced with the cold drink in comparison with the warm drink (P = 0.023). TEA improved the impaired gastric accommodation from 539.2 ± 133.8 ml to 731.0 ± 185.7 ml (P = 0.005). 2) The percentage of normal gastric slow waves in six subjects was significantly decreased in the cold session (P = 0.002) and improved in the TEA session (P = 0.009 vs sham; P < 0.001 vs cold). 3) TEA showed significant improvement in the bloating (80.8 ± 5.7 vs 61.2 ± 26.2, P = 0.011), postprandial fullness (48.1 ± 12.0 vs 34.2 ± 21.2, P = 0.042), and nausea (29.6 ± 10.9 vs 19.2 ± 11.2, P = 0.026) in comparison with sham-TEA session. 4) Neither cold drink nor TEA altered vagal activities (P > 0.05). CONCLUSIONS: TEA improves impaired gastric accommodation and slow waves induced by cold drink and the effect does not seem to be mediated via the vagal mechanisms.

Ameliorating Effect of Transcutaneous Electroacupuncture on Impaired Gastric Accommodation in Patients with Postprandial Distress Syndrome-Predominant Functional Dyspepsia: A Pilot Study.

Patients with functional dyspepsia (FD) have both reduced gastric accommodation and impaired gastric motility that are difficult to treat. The aim of this study was to investigate the therapeutic potential of transcutaneous electroacupuncture (TEA) for both of these disorders in FD patients. Acute experiments were performed in FD patients to study the effect of TEA and sham-TEA on gastric accommodation assessed by a nutrient drink test and gastric motility assessed by the measurement of the electrogastrogram (EGG). TEA or sham-TEA was performed via cutaneous electrodes at acupoints ST36 and PC6 or sham-points nonacupoints. It was found that (1) gastric accommodation (maximum tolerable volume) was reduced in FD patients compared with the controls (P < 0.03). TEA improved gastric accommodation in FD patients (P < 0.02). (2) Acute TEA significantly increased the percentage and power of normal gastric slow waves in the fed state assessed in the FD patients by the EGG in comparison with sham-TEA. (3) TEA increased vagal activity assessed by the spectral analysis of the heart rate variability in the fed state in FD patients. It was concluded that needleless method of transcutaneous electroacupuncture may have a therapeutic potential for treating both impaired gastric accommodation and impaired gastric motility in patients with FD.

Efficacy of Adaptive Biofeedback Training in Treating Constipation-Related Symptoms.

Biofeedback therapy is a well-known and effective therapeutic treatment for constipation. A previous study suggested that adaptive biofeedback (ABF) training was more effective than traditional (fixed training parameters) biofeedback training. The aim of this study was to verify the effectiveness of ABF in relieving constipation-related symptoms. We noticed that in traditional biofeedback training, a patient usually receives the training twice per week. The long training sessions usually led to poor compliance. This study proposes an intensive biofeedback therapy and compares intensive therapy with nonintensive therapy in patients with constipation-related symptoms. Methods. 63 patients with constipation-related symptoms were treated with ABF between 2012 and 2013. These patients were further divided into the intensive therapy and nonintensive therapy groups. Results. A total of 63 patients were enrolled in the study, including 24 in the nonintensive therapy group and 39 in the intensive therapy group. 100% (N = 21) of constipation patients achieved the primary efficacy endpoint (≥3 bowel movements/week). There was significant improvement in constipation-related symptoms after adaptive biofeedback. The intensive biofeedback therapy did not show better performance compared to nonintensive biofeedback therapy. Conclusions. This investigation provides support for the efficacy of biofeedback for constipation-related symptoms. The efficacy of intensive therapy is similar to nonintensive therapy.

Ameliorating effects and autonomic mechanisms of needle-less transcutaneous electrical stimulation at ST36 on stress-induced impairment in gastric slow waves.

BACKGROUND AND AIM: Stress has long been documented to alter gastrointestinal motility. The effects of electroacupuncture (EA) on stress and gastric motility are relatively well known; however, whether EA has an ameliorating effect on stress-induced dysmotility remained unclear. This study aims to investigate the effects and mechanisms of needle-less transcutaneous electroacupuncture (TEA) on stress-induced impairment in gastric slow waves. METHODS: A watch-size digital stimulator was developed. Ten healthy volunteers were involved in a four-session study (control, cold stress, TEA, and sham TEA). Electrogastrograpy was used to assess gastric slow waves, and electrocardiogram was recorded for the assessment of autonomic functions. The recordings were made in each session with/without stress and with TEA at ST36 or sham points. RESULTS: The results are as follows: (i) Cold stress-induced gastric dysrhythmia and impaired normal slow waves (P < 0.01). TEA showed a preventive effect on cold stress-induced impairment in gastric slow waves. TEA at ST36, but not sham TEA, normalized slow waves (P = 0.03 vs stress; P = 0.44 vs control), attributed to the suppression of gastric dysrhythmia; (ii) Postprandially, there was a decrease in vagal activity in both control (P = 0.004) and stress (P = 0.002) sessions; this decrease was prevented with TEA (P < 0.05). Similarly, there was a postprandial increase in sympathetic activity in both control (P = 0.01) and stress (P = 0.002) sessions, and this increase was suppressed with TEA. CONCLUSIONS: Needle-less TEA at ST36 using a watch-size stimulator is able to improve stress-induced impairment in gastric slow waves, possibly mediated via the autonomic mechanism. Home-based needle-less TEA may be a viable therapy for stress-induced impairment in gastric motility functions.

Transcutaneous Neuromodulation at Posterior Tibial Nerve and ST36 for Chronic Constipation.

The aims of this study were to investigate the effects and possible mechanisms of transcutaneous neuromodulation (TN) in patients with chronic constipation. Twelve patients were recruited. The treatment consisted of 2-week TN and 2-week sham-TN which was performed in a crossover design. Bowel habit diary, Patient Assessment of Constipation Symptom (PAC-SYM), Patient Assessment of Constipation Quality of Life (PAC-QOL), and anorectal motility were evaluated. Electrocardiogram was recorded for the assessment of autonomic function during acute TN therapy. It was found that (1) TN improved the frequency of spontaneous defecation. After 2-week TN therapy, 83% patients had more than 3 times bowel movements per week which was significantly different from sham-TN (P = 0.01). (2) TN improved PAC-SYM and PAC-QOL scores (P < 0.001, resp.). (3) TN significantly decreased the threshold volume to elicit RAIR (P < 0.05), ameliorated rectal sensory threshold (P = 0.04), and maximum tolerance (P = 0.04). (4) TN, but not sham-TN, increased the vagal activity (P = 0.01 versus baseline) and decreased the sympathetic activity (P = 0.01, versus baseline). It was concluded that needleless TN at posterior tibial nerve and ST36 using a watch-size stimulator is effective in chronic constipation, and the effect was possibly mediated via the autonomic mechanism.

[Inhibitory effects of Scutellaria barbatae D. Don on tumor angiogenesis and its mechanism].

BACKGROUND & OBJECTIVE: Various chemically synthetic anti-angiogenesis agents have serious side effects. The traditional Chinese medicine has attracted considerable attention because of its low toxicity. This study was to explore the inhibitory effects of Scutellaria barbatae D. Don, a kind of traditional Chinese medicinal anti-cancer herb, on tumor angiogenesis, and investigate its mechanism. METHODS: Matrigel plug and human umbilical vascular endothelial cells (HUVECs) were used to construct in vivo and in vitro models of angiogenesis to assess the effect of Scutellaria barbatae D. Don on angiogenesis. After cultured with Scutellaria barbatae D. Don, the migration of endothelial cells was examined by Transwell chamber; the expression of vascular endothelial growth factor (VEGF) in HeLa cells was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Scutellaria barbatae D. Don significantly inhibited angiogenesis in Matrigel; the tube formation number was significantly lower in 20% and 40% medicated serum groups containing Scutellaria barbatae D. Don than in 20% and 40% drug-free serum groups (5.6+/-1.1 vs. 9.8+/-1.3, P=0.001; 1.0+/-0.7 vs. 13.4+/-1.1, P<0.001). Migrated endothelial cells was significantly fewer in 20% and 40% medicated serum groups containing Scutellaria barbatae D. Don than in 20% and 40% drug-free serum groups (19.75+/-2.63 vs. 24.25+/-2.06, P=0.038; 14.00+/-2.58 vs. 26.5+/-4.65, P=0.006). When treated for 24 h and 48 h, the expression of VEGF in HeLa cells was significantly lower in 40% medicated serum group containing Scutellaria barbatae D. Don than in 40% drug-free serum group (138.67+/-9.50 vs. 195.82+/-2.43, P=0.006; 93.84+/-41.11 vs. 193.68+/-18.37, P=0.036). CONCLUSION: Scutellaria barbatae D. Don could efficiently inhibit angiogenesis in tumor tissue which might relate with inhibition of endothelial cell migration and down-regulation of VEGF in tumor cells.