[Effects and mechanism of human umbilical vein endothelial cells-derived exosomes on wound healing in diabetic rabbits].

Objective: The investigate the effects and mechanism of exosomes derived from human umbilical vein endothelial cells (HUVECs) on wound healing in diabetes rabbits. Methods: The experimental research methods were used. The primary vascular endothelial cells (VECs) and human skin fibroblasts (HSFs) were extracted from skin tissue around ulcer by surgical excision of two patients with diabetic ulcer (the male aged 49 years and the female aged 58 years) admitted to Xiangya Third Hospital of Central South University in June 2019. The cells were successfully identified through morphological observation and flow cytometry. The HUVEC exosomes were extracted by ultracentrifugation and identified successfully by morphological observation, particle size detection, and Western blotting detection. Twenty female 3-month-old New Zealand rabbits were taken to create one type 2 diabetic full-thickness skin defect wound respectively on both sides of the back. The wounds were divided into exosomes group and phosphate buffer solution (PBS) group and treated accordingly, with 20 wounds in each group, the time of complete tissue coverage of wound was recorded. On PID 14, hematoxylin-eosin staining or Masson staining was performed to observe angiogenesis or collagen fiber hyperplasia (n=20). The VECs and HSFs were co-cultured with HUVEC exosomes for 24 h to observe the uptake of HUVEC exosomes by the two kinds of cells. The VECs and HSFs were divided to exosome group treated with HUVEC exosomes and PBS group treated with PBS to detect the cell proliferation on 4 d of culture with cell count kit 8, to detect and calculate the cell migration rate at 24 and 48 h after scratch by scratch test, to detect the cell migration number at 24 h of culture with Transwell test, and to detect the mRNA expressions of nuclear factor-erythroid 2-related factor 2 (NRF2) and transcription activating factor 3 (ATF3) by real time fluorescence quantitative reverse transcription polymerase chain reaction. Besides, the number of vascular branches and vascular length were observed in the tube forming experiment after 12 h of culture of VECs (n=3). The VECs and HSFs were taken and divided into PBS group and exosome group treated as before, and NRF2 interference group, ATF3 interference group, and no-load interference group with corresponding gene interference. The proliferation and migration of the two kinds of cells, and angiogenesis of VECs were detected as before (n=3). Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, independent sample t test, and least significant difference test. Results: The time of complete tissue coverage of wound in exosome group was (17.9±1.9) d, which was significantly shorter than (25.2±2.3) d in PBS group (t=4.54, P<0.05). On PID14, the vascular density of wound in PBS group was significantly lower than that in exosome group (t=10.12, P<0.01), and the collagen fiber hyperplasia was less than that in exosome group. After 24 h of culture, HUVEC exosomes were successfully absorbed by VECs and HSFs. The proliferative activity of HSFs and VECs in exosome group was significantly higher than that in PBS group after 4 d of culture (with t values of 54.73 and 7.05, respectively, P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs (with t values of 3.42 and 11.87, respectively, P<0.05 or P<0.01) and VECs (with t values of 21.42 and 5.49, respectively, P<0.05 or P<0.01) in exosome group were significantly higher than those in PBS group. After 24 h of culture, the migration numbers of VECs and HSFs in exosome group were significantly higher than those in PBS group (with t values of 12.31 and 16.78, respectively, P<0.01). After 12 h of culture, the mRNA expressions of NRF2 in HSFs and VECs in exosome group were significantly higher than those in PBS group (with t values of 7.52 and 5.78, respectively, P<0.05 or P<0.01), and the mRNA expressions of ATF3 were significantly lower than those in PBS group (with t values of 13.44 and 8.99, respectively, P<0.01). After 12 h of culture, the number of vascular branches of VECs in exosome group was significantly more than that in PBS group (t=17.60, P<0.01), and the vascular length was significantly longer than that in PBS group (t=77.30, P<0.01). After 4 d of culture, the proliferation activity of HSFs and VECs in NRF2 interference group was significantly lower than that in PBS group and exosome group (P<0.05 or P<0.01); the proliferation activity of HSFs and VECs in ATF3 interference group was significantly higher than that in PBS group (P<0.05 or P<0.01) and significantly lower than that in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in ATF3 interference group were significantly higher than those in PBS group (P<0.05 or P<0.01) and significantly lower than those in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in NRF2 interference group were significantly lower than those in PBS group and exosome group (P<0.05 or P<0.01). After 24 h of culture, the migration numbers of VECs and HSFs in ATF3 interference group were significantly more than those in PBS group (P<0.05) and significantly less than those in exosome group (P<0.05 or P<0.01); the migration numbers of VECs and HSFs in NRF2 interference group were significantly less than those in PBS group and exosome group (P<0.01). After 12 h of culture, the vascular length and number of branches of VECs in NRF2 interference group were significantly decreased compared with those in PBS group and exosome group (P<0.01); the vascular length and number of branches of VECs in ATF3 interference group were significantly increased compared with those in PBS group (P<0.01) and were significantly decreased compared with those in exosome group (P<0.01). Conclusions: HUVEC exosomes can promote the wound healing of diabetic rabbits by promoting the proliferation and migration of VECs and HSFs, and NRF2 and ATF3 are obviously affected by exosomes in this process, which are the possible targets of exosome action.

Efficacy of needleless transcutaneous electroacupuncture in synchronization with breathing for symptomatic idiopathic gastroparesis: A blinded and controlled acute treatment trial.

BACKGROUND: Needleless transcutaneous electroacupuncture (TEA) improves nausea and myoelectrical activity in diabetic gastroparesis (GP). Synchronized TEA (STEA), which combines synchronized breathing with TEA, is more potent than TEA in enhancing vagal activity in healthy subjects. AIMS: To investigate whether STEA improves symptoms, electrogastrogram (EGG) and vagal activity in idiopathic gastroparesis (IGP). METHODS: Eighteen IGP subjects underwent 2 randomized visits (sham at non-acupoints or real STEA at acupoints) consisted of a 30-minute baseline, an Ensure challenge to provoke nausea, followed by 60-minute treatment with sham or real STEA, and 15-minute observation period. Severity of nausea, EGG, and vagal activity (based on electrocardiogram and serum Pancreatic Polypeptide, PP) were recorded. RESULTS: In sham or STEA, the nausea scores of 2.7 ± 0.5 and 1.9 ± 0.5 at fasting baseline, respectively, increased to 5.9 ± 0.4 and 5.8 ± 0.3 during Ensure test (P < .05, vs baseline), subsequently reduced to 3.4 ± 0.6 with sham or 3.6 ± 0.6 with STEA, respectively (P < .05, vs Ensure period). Experiments with sham and STEA started with similar % of normal waves on EGG (66.4 ± 3.9 and 61.8 ± 3.0, respectively); decreased to 63. 5 ± 4.1 and 58.2 ± 2.8 during the Ensure test. After STEA, there was ~24% increase in % of normal waves, significantly different from the sham (6.0%) (P < .01). In sham or STEA, vagal activity was identical at baseline and after the Ensure. STEA induced a 3-fold increase in vagal activity compared with sham (P < .01). Ensure increased serum PP levels, and both treatments decreased the PP CONCLUSIONS: In IGP, STEA is not superior to Sham in decreasing nausea, but is more effective in improving gastric dysrhythmia.

[Schwannoma of the ethmoid sinus in children: a case report].

A ten years old male patient，the main symptom was prsented as the left nasal obstruction, repeated hemorrhage with hyposmia. Large translucent neoplasm can be seen in the left side of the nasal cavity. CT and MRI of the nasal sinus showed that the soft tissue density shadow in the left side of the ethmoid sinus and the surrounding bone with no damage. He was treated with nasal endoscopic surgery. Postoperative pathology showed schwannoma. The tumor recurred three years later, and the patient underwent nasal endoscopic surgery again. In the literature we reviewed the case to analyze the reasons of recurrence.

[The expericence of diagnosis and treatment of foreign body within the pharyngeal soft tissue(3 cases)].

Through the diagnosis and treatment of the foreign body in the soft tissue of phargnx,reduce missed diagnosis. Flexible using of imaging methods for diagnosis and localization,and selecting the best surgical approach are important.

The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains.

Nuclear factor erythroid 2-related factor 2 (Nrf2, NM 006164, 605 AA) is essential for the antioxidant responsive element (ARE)-mediated expression of a group of detoxifying antioxidant genes that detoxify carcinogens and protect against oxidative stress. Several proteins have been identified as Nrf2-interacting molecules. In this study, we found that the overexpression of receptor-associated coactivator 3 (RAC3)/AIB-1/steroid receptor coactivator-3, a nuclear coregulator and oncogene frequently amplified in human breast cancers, induced heme oxygenase-1 (HO-1) through Nrf2 transactivation in HeLa cells. Next, we determined the interaction between RAC3 and Nrf2 proteins using a co-immunoprecipitation assay and fluorescence resonance energy transfer analysis. The results showed that RAC3 bound directly to the Nrf2 protein in the nucleus. Subsequently, we identified the interacting domains of Nrf2 and RAC3 using a glutathione S-transferase pull-down assay. The results showed that both the N-terminal RAC3-pasB and C-terminal RAC3-R3B3 domains were tightly bound to the Neh4 and Neh5 transactivation domains. Furthermore, chromatin immunoprecipitation showed that RAC3 bound tightly to the ARE enhancer region of the HO-1 promoter via Nrf2 binding. These data suggest that Nrf2 activation is modulated and directly controlled through interactions with the RAC3 protein in HeLa cells.

Prognostic improvement of reexcision for positive resection margins in patients with advanced gastric cancer.

AIM: The aim of this study was to investigate the effect of reexcision for advanced gastric cancer (GC) with positive resection margins on prognosis and to identify the selection criteria for the reexcision of patients with positive margins. PATIENTS AND METHODS: This was a retrospective study of 122 patients with positive margins who underwent potentially curative resection for locally advanced GC. The clinicopathological factors and survival among 50 patients who were reexcised to a negative resection margin (NR group) and 72 patients who were left with a positive resection margin (PR group) were compared using univariate and multivariate analyses. RESULTS: Median survival in the PR group was 18 months compared with 23 months in the NR group (p = 0.019). In the ≤ pN2-category subset, the PR group had a significantly worse prognosis compared with the NR group (median survival of 25 months vs. 44 months; p = 0.021). This difference was not observed in the pN3-category subset. In the univariate analysis, variables including pTNM stage, pN-category, and positive resection margin had adverse effects on OS among the entire population of 122 patients. A positive margin was confirmed as an independent prognostic factor for OS in the multivariate analysis. CONCLUSIONS: The reexcision of a positive margin improves the prognosis of patients with advanced GC, especially in those paitents with ≤ pN2-category disease and in patients undergoing D2 lymphadenectomy. Obtaining routine frozen sections of samples from the resection margin should be mandatory in the treatment of all GC patients undergoing potentially curative surgery.

Survival benefits of metabolic syndrome among older men aged 75 years and over in Taiwan.

BACKGROUND: Metabolic syndrome (MetS) was common in the elderly, but its prognostic significance in older old population remained unclear. The main purpose of this study was to evaluate the survival impact of MetS among older men aged 75 and over in Taiwan. METHODS: From 2008, residents aged 75 years and older of Banciao Veterans Home were invited for study and were followed for 3 years. All participants received history taking, physical examinations, and laboratory tests. Mortality was determined by Veteran Affairs Death Registry, which was linked to the National Death Registry. RESULTS: Overall, 680 men (mean age: 82.5±4.7 years) were enrolled for study and the prevalence of MetS was 31.6%. During the follow-up period, 140 (20.6%) participants died, and the causes of death included infectious diseases (62, 9.1%), cardiovascular disease (37, 5.4%), cancer (20, 2.9%), and others (21, 3.1%). MetS subjects had a significantly higher prevalence of hypertension, diabetes mellitus, and having higher body mass index, waist circumferences, systolic blood pressure, fasting blood glucose, serum triglyceride and lower HDL-C level than non-MetS subjects. However, MetS subjects were less likely to die during study period (16.3% vs. 22.6%, P=0.059). Multivariate logistic regression showed that older age (OR:1.04, 95% C.I.: 1.00-1.08, P=0.04), diabetes mellitus (OR: 2.10, 95% CI: 1.34-3.30, P=0.001) were independent risk factors for mortality; and serum total cholesterol and triglyceride were protective factors (OR: 0.99, 95% CI: 0.99-1.00, P=0.037 for cholesterol; OR: 0.99, 95% CI: 0.99-1.00, P=0.013 for triglyceride). Adjusted for age, diabetes mellitus, serum levels of total cholesterol, and triglyceride, MetS played a potential trend of survival benefits among study subjects (HR: 0.71, 95% CI: 0.45-1.12, P=0.144). CONCLUSIONS: The prevalence of MetS among men aged 75 years and over was 31.6%, and the 3-year mortality rate was 20.6%. Older age, diabetes mellitus, lower serum cholesterol and lower serum triglyceride were independent risk factors for mortality. Further investigation is needed to clarify the prognostic impact of MetS in older adults.

Fractionation of volatile constituents from curcuma rhizome by preparative gas chromatography.

A preparative gas chromatography (pGC) method was developed for the separation of volatile components from the methanol extract of Curcuma rhizome. The compounds were separated on a stainless steel column packed with 10% OV-101 (3 m × 6 mm, i.d.), and then, the effluent was split into two gas flows. One percent of the effluent passed to the flame ionization detector (FID) for detection and the remaining 99% were directed to the fraction collector. Five volatile compounds were collected from the methanol extract of Curcuma rhizome (5 g/mL) after 83 single injections (20 uL) with the yield of 5.1-46.2 mg. Furthermore, the structures of the obtained compounds were identified as ß-elemene, curzerene, curzerenone, curcumenol, and curcumenone by MS and NMR spectra, respectively.

Short pulse gastric electrical stimulation for cisplatin-induced emesis in dogs.

BACKGROUND: In a previous study, we investigated the ameliorating effect of gastric electrical stimulation (GES) with a single set of parameters on emesis and behaviors suggestive of nausea induced by cisplatin in dogs. The aim of this study was to investigate the effects of GES with different parameters on cisplatin-induced emesis in dogs. METHODS: Seven dogs implanted with gastric serosal electrodes were studied in six randomized sessions: one control session with cisplatin (2 mg kg(-1)) and five sessions with cisplatin plus GES of different parameters: GES-A: 14 Hz, 5 mA, 0.3 ms, 0.1 s on and 5 s off; GES-B: increased frequency and on-time; GES-C: increased frequency; GES-D: increased frequency and pulse width; and GES-E: increased frequency and amplitude. Gastric slow waves and emetic responses were recorded in each session. KEY RESULTS: (i) Cisplatin induced emetic responses and gastric dysrhythmia. The peak time of the emetic response was during the fourth hour after cisplatin. (ii) GES with appropriate parameters reduced cisplatin-induced emesis. The number of vomiting times during the 6 h after cisplatin was 7.0 ± 1.4 in the control, 4.7 ± 1.2 with GES-A (P = 0.179), 4.2 ± 1.2 with GES-B (P = 0.109), 7.0 ± 0.8 with GES-C (P = 0.928), 2.1 ± 0.3 with GES-D (P = 0.005) and 4.7 ± 1.5 with GES-E (P = 0.129). However, none of the GES parameters could improve gastric dysrhythmia. CONCLUSIONS & INFERENCES: Gastric electrical stimulation with appropriate parameters reduces cisplatin-induced emetic responses and behaviors suggestive of nausea in dogs. Among the tested parameters, GES with increased pulse width seems to produce better relief of cisplatin-induced emesis.

Separation of circulating cancer cells by unique microfluidic chip in colorectal cancer.

Circulating tumor cells (CTCs) from peripheral blood are emerging as a useful tool for the detection of malignancy, monitoring disease progression, and measuring response to therapy. We describe a unique microfluidic chip that was capable of efficient and selective separation of CTCs from peripheral whole blood samples. The ability of microfluidic chip to capture CTCs from PBS and whole blood samples was tested. Sixty-eight peripheral blood samples from 68 colorectal cancer patients were investigated for the presence of CTCs by microchip technology. The frequency of CTCs was analyzed statistically for correlation with relevant clinical data. We also examined samples from 20 healthy individuals as controls. The calculated capture efficiency was 85.7% and decreased significantly at flow rates above 2.0 ml/h. The number of CTCs isolated ranged from 3 to 236/ml for colorectal patients [99 +/- 64 (mean +/- SD) CTCs/ml]. None of the 20 healthy subjects had any identifiable CTCs. We identified CTCs in 46 (67.65%) of the 68 patients: in two of nine (22.22%) Dukes A, in 10 of 24 (41.67%) Dukes B, in 21 of 22 (95.45%) Dukes C, and in all 13 Dukes D patients. The detection rate in Dukes C and D patients was much higher than in Dukes A and B patients (97.73% vs. 36.36%) (p < 0.01). A significant correlation between detection of CTCs and clinical stage (r = 0.792, p < 0.01) was found, which was higher than carcinoembryonic antigen (r = 0.285, p > 0.01), carbohydrate antigen 19-9 (r = 0.258, p > 0.01), alpha-fetoprotein (r = 0.096, p > 0.01), and cancer antigen 125 (r = 0.134, p > 0.01). Microfluidic chip provides a novel method for capturing CTCs. The presence of CTCs correlated with clinical stage. It is important to evaluate CK-positive and DAPI-stained tumor cells together to determine the role of CTCs in tumor behavior and disease progression.

Hepatic electrical stimulation reduces blood glucose in diabetic rats.

BACKGROUND: The aim of this study was to investigate the feasibility and mechanisms of controlling blood glucose using hepatic electrical stimulation (HES). METHODS: The study was performed in regular Sprague-Dawley (SD) rats, streptozotocin-induced type 1 diabetic rats and Zucker diabetic fatty (ZDF) rats chronically implanted with one pair of stimulation electrodes on two lobes of the liver tissues. KEY RESULTS: (i) Hepatic electrical stimulation was effective in reducing blood glucose by 27%-31% at time points 60, 75 and 90 min after oral glucose in normal rats; (ii) HES reduced blood glucose in both fasting and fed states in both type 1 and type 2 diabetic rats; (iii) Chronic HES decreased the blood glucose level, and, delayed gastric empty and increased plasma glucagon-like peptide-1 (GLP-1) level; and (iv) No adverse events were noted in any rats during HES. Histopathological analyses and liver function tests revealed no electrode dislodgement, tissue damages or liver enzyme changes with HES. CONCLUSIONS & INFERENCES: Hepatic electrical stimulation is capable of reducing both fasting and fed blood glucose in normal, and type 1 and type 2 diabetic rats and the effect may be partially mediated via an increase in GLP-1 release.

Gastric slow waves, gastrointestinal symptoms and peptides in systemic sclerosis patients.

Impaired gastric slow waves, frequent gastrointestinal (GI) symptoms and altered GI peptides have been reported in Scleroderma (SSc) patients. The aim of this study was to investigate the associations among these three important components in GI dysmotility. Seventeen fasted SSc patients underwent four channel surface electrogastrography, measuring % of normal gastric slow waves or dysrhythmia. Patients completed a questionnaire designed by us to assess demographics, upper and lower GI symptoms (symptom presence, frequency and impact on quality of life, QOL), by YES/NO, Likert Scales and Visual Analogue Scales 1-100 mm (called GI Dysmotility Questionnaire, GIDQ) and health-related QOL by SF-36. Fasting plasma vasoactive intestinal peptide (VIP) and motilin levels were measured by peptide immunoassays. There were significant correlations between percentages of gastric dysrhythmias (bradygastria or arrhythmia) and a number of major GI symptoms such as nausea, abdominal bloating and pain. The plasma level of VIP was correlated positively with % dysrhythmia but negatively with % normal slow waves. Motilin was positively correlated with slow wave coupling (coordination). No major differences were noted in the measured peptides or gastric slow waves between limited SSc and diffuse SSc. Correlations were noted between SF-36 domain scores and our GIDQ scores. In SSc patients, gastric dysrhythmias are correlated with certain GI symptoms. Correlations are also noted between plasma VIP/Motilin levels and gastric slow waves. Thus in SSc, gastric dysrhythmias may be predictive of development of certain dyspeptic symptoms. Plasma VIP may be involved in the development of dysrhythmias.

Effect of intestinal pacing on small bowel transit and nutrient absorption in healthy volunteers.

BACKGROUND: Intestinal pacing (IP) has been previously shown to delay gastric emptying and reduce food intake in animals. The aims of this study were to investigate the effect and mechanism of IP on nutrient absorption in healthy volunteers. METHODS: Twelve healthy volunteers (six men, six women) were involved in a two-session (one session without IP and one with IP) study. At the beginning of each session, a nasal-duodenal feeding tube, with two ring electrodes (used for IP) on the tip of the tube, was incubated into the duodenum under endoscopy. After a complete recovery from the incubation, the duodenum was infused via the feeding tube with 150 ml 30% intralipid + 25 g D-xylose within 30 min, and the stool was collected for 24 h for the analysis of fecal lipid during which a controlled meal was taken. Then 100 ml 1mCi(99)Tc-labeled non-absorbable solution was infused within 3 min. The subject was asked to lie under a gamma camera for at least 1 h for the measurement of small bowel transit. The movement of isotopes was monitored by gamma camera at an interval of 10 s. The first appearance of isotopes in the cecum was considered as small intestinal transit time. The order of the two sessions was randomized and 1 week apart. In the IP session, intestinal pacing was performed via the pair of the ring electrodes for 2 h initiated at the beginning of infusion with a pacing frequency of 13 pulses/min, pulse width of 300 ms and amplitude of 5 mA. RESULTS: (1) IP significantly reduced lipid and D-xylose absorption. The fecal lipid was 6.6 +/- 4.6 g without IP and almost doubled with IP (11.1 +/- 6.5 g, P = 0.047). Similarly, the D-xylose in urine was 3.46 +/- 2.22 g with IP, which was significantly lower than that without IP (6.63 +/- 5.06 g, p = 0.049). (2) IP accelerated intestinal transit. The transit time was 39 +/- 17 min in the control session and reduced to 28 +/- 10 min in the IP session (p < 0.03). (3) Diarrhea was reported in one subject without IP but in six subjects with IP (p < 0.05). CONCLUSIONS: The increased fecal lipid and induction of diarrhea with intestinal pacing suggest that intestinal pacing is capable of inducing malabsorption. This effect maybe contributed to the acceleration of intestinal transit.

Cisplatin-induced gastric dysrhythmia and emesis in dogs and possible role of gastric electrical stimulation.

The aim of this study was to investigate the effect of cisplatin on gastric myoelectrical activity and the role of gastric electrical stimulation in the treatment of cisplatin-induced emesis in dogs. Seven dogs implanted with electrodes on the gastric serosa were used in a two-session study. Cisplatin was infused in both the control session and the gastric electrical stimulation session, and gastric electrical stimulation was applied in the gastric electrical stimulation session. Gastric slow waves and emesis, as well as behaviors suggestive of nausea, were recorded during each session. The results were as follows: (1) cisplatin induced vomiting and other symptoms and induced gastric dysrhythmia. The percentage of normal slow waves decreased significantly during the 2.5 h before vomiting (P=0.01) and the period of vomiting (P<0.001). (2) Gastric electrical stimulation reduced emesis and the symptoms score. The total score in the control session was higher than that in the gastric electrical stimulation session (P=0.02). However, gastric electrical stimulation had no effects on gastric dysrhythmia. It is concluded that cisplatin induces emesis and gastric dysrhythmia. Gastric electrical stimulation may play a role in relieving chemotherapy-induced emetic responses and deserves further investigation.

Involvement of the hippocampus and neuronal nitric oxide synthase [correction of synapse] in the gastric electrical stimulation therapy for obesity.

BACKGROUND: Gastric electrical stimulation (GES) has been introduced for treating obesity. However, possible central mechanisms remain to be revealed. Hippocampus has been shown to be involved in the regulation of gastrointestinal functions. Changes in hypothalamic neuronal nitric oxide synthase (nNOS) have been observed in genetically obese rodents. The aim of this study was to investigate the involvement of nNOS with GES in the rodent hippocampus. METHODS: The effect of GES on gastric distension (GD) neurons was investigated using four different sets of parameters (GES-A, pulse train of standard parameters; GES-B, reduced on time; GES-C, increased pulse width, and GES-D: reduced pulse frequency), and the expression of nNOS in hippocampus was observed by fluoimmunohistochemistry staining. RESULTS: CA1 region neurons (90.8%) responded to GD, 50.6% of which showed excitation (GD-E neurons) and 49.4% showed inhibition (GD-I neurons). Most of GD-responsive neurons (63.3%) were excited with GES. The response to GES was associated with stimulation strength, pulse width and frequency. GD-E neurons (62.5%, 76.9%, 100%, and 62.3%) and GD-I (63.6%, 47.1%, 85.7% and 50.0%) showed excitatory responses to GES-A, GES-B, GES-C, and GES-D, respectively (P < 0.05, GES-C vs. others). nNOS immunoreactive (nNOS-IR) positive neurons were observed in hippocampus CA1, CA2-3 regions and the dentate gyrus. The expression of nNOS-IR positive neurons was significantly decreased in CA1 and CA2-3 region (P < 0.05) after GES (para-C) for 2 h. CONCLUSIONS: Excitation of GD-responsive neurons and reduced expression of nNOS in the hippocampus are indicative of the central effect of GES.

A novel method of 2-channel dual-pulse gastric electrical stimulation improves solid gastric emptying in dogs.

BACKGROUND: Gastric electrical stimulation (GES) is known to improve vomiting with short pulses, normalize dysrhythmia with long pulses, and accelerate gastric emptying with 2 channels. The aim of this study was to assess the effects of a new method GES, namely, 2-channel GES with dual pulses on gastric emptying of solids as well as gastric dysrhythmia and emetic responses. METHODS: Seven beagle dogs implanted with 4 pairs of electrodes were studied. A novel method of GES was proposed: 2-channel dual-pulse GES in which each stimulus was composed of a short pulse followed with a long pulse, and stimulation was delivered at 2 different locations. The study was performed to test the effects of this new method of GES on vasopressin-induced delayed gastric emptying of solids, gastric dysrhythmia, and emetic responses. RESULTS: (1) Vasopressin-induced gastric dysrhythmia and emetic responses, as well as delayed gastric emptying of solids (P < .01). (2) Two-channel, but not 1-channel, dual-pulse GES was able to accelerate vasopressin-induced delayed gastric emptying of solids. (3) Both 1- and 2-channel dual-pulse GES was capable of improving dysrhythmia and emetic responses (P < .01). CONCLUSIONS: The novel method of 2-channel dual-pulse GES is capable of accelerating gastric emptying of solids and improving dysrhythmia and emetic responses induced by vasopressin. This new method of GES may have a potential for gastroparesis.

Percutaneous transhepatic gall bladder drainage: a better initial therapeutic choice for patients with gall bladder perforation in the emergency department.

OBJECTIVES: To investigate clinical features and outcomes in patients with acute cholecystitis with gall bladder perforation receiving open cholecystectomy or percutaneous transhepatic gall bladder drainage in the emergency department. METHODS: From 1996 through 2005, 33 patients with non-traumatic gall bladder perforation, among 585 patients with acute cholecystitis, were enrolled. Patients were divided into two groups: open cholecystectomy in 16 patients and percutaneous transhepatic gall bladder drainage in 17 patients. Medical records, including demographic data, past history of systemic diseases or gallbladder stones, initial clinical presentations, laboratory data, physical status, therapeutic interventions, and outcomes, were analysed. RESULTS: Mean patient age was 72.6 years (range 54-92 years). 28 patients (84.8%) were male. Median time of symptom onset before emergency department diagnosis was 5 days (range 0.5-30 days). Estimated incidence of gall bladder perforation was 5.6% (33/585). 27 patients (81.8%) had gallstones operatively or in image studies. All patients had either right upper quadrant pain/tenderness or epigastric pain/tenderness. Only 9 (27.3%) patients had positive Murphy's sign. Six patients in the percutaneous transhepatic gall bladder drainage group received further open cholecystectomy. Overall mortality was 24.2% (8/33). The direct cause of death was disease related sepsis in all patients. Patients receiving percutaneous transhepatic gall bladder drainage had a higher survival rate than those receiving open cholecystectomy (100% vs 50%, p<0.001). No differences in complications and length of hospital stay of survivors were observed between groups. CONCLUSIONS: In this study, we delineated clinical features of patients with gall bladder perforation. Better clinical outcome is observed for percutaneous transhepatic gall bladder drainage, and this is suggested as an initial therapeutic choice, especially in high risk patients who are likely to need surgery.

Induction of heme oxygenase-1 improves impaired intestinal transit after burn injury.

BACKGROUND: Burn injury has been shown to impair intestinal transit. The induction of heme oxygenase (HO)-1, the rate-limiting enzyme in heme degradation, has been demonstrated to provide protection against various injuries. The aim of this study was to investigate whether the induction of HO-1 by hemin would improve impaired intestinal transit after burn injury. METHODS: Burn/sham rats were divided into 3 groups: saline solution, hemin (HO-1 inducer), and hemin plus tin protoporphyrin IX. Intestinal transit was measured with the use of phenol red and assessed with the geometric center. The gene and/or protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1beta, HO-1, and p38 mitogen-activated protein kinase (p38 MAPK) was measured by real-time polymerase chain reaction and/or by Western blot analysis. RESULTS: Intestinal transit was delayed with burn injury and improved significantly with the induction of HO-1; burn injury significantly activated p38 MAPK and myeloperoxidase and increased gene and/or protein expression of iNOS, COX-2, IL-1beta, and HO-1. The administration of hemin led to a significant decrease in the activation of p38 MAPK and myeloperoxidase and the gene and/or protein expression of iNOS, COX-2, and IL-1beta. CONCLUSION: The induction of HO-1 improves burn-induced delayed intestinal transit. The beneficial effect of hemin treatment could be linked, at least in part, to the down-regulation of iNOS, COX-2, and IL-1beta expression, which suggests that the induction of HO-1 may provide an effective therapeutic measure for gut dysmotility after burn injury.