[Analysis of safety and efficacy of laparoscopic surgery for gallbladder carcinoma].

Objective: To examine the efficacy and safety of laparoscopic surgery for gallbladder carcinoma. Methods: The data of 197 gallbladder carcinoma patients admitted at Peking Union Medical College Hospital between January 2012 and September 2022 were analyzed retrospectively. There were 86 males and 111 females,with age of (64.4±9.8)years(range:35 to 89 years). Patients were divided into laparoscopic group(n=53) and open group(n=144) according to different surgical methods. The general information of the two groups were matched by propensity score matching,and the clinical data and prognosis were compared between the two groups. Categorical variables were analyzed using χ2 test or Fisher's exact test,as appropriate. Continuous variables with and without normal distribution were analyzed using t-test and Mann-Whitney U test,respectively. Kaplan-Meier curves with Log-rank test were used to analyze the cumulative survival rates. Results: Forty-eight pairs of patients were matched successfully. There was no difference in general information,cholecystolithiasis,partial hepatectomy,and tumor stage between two groups(all P>0.05). The laparoscopic group had shorter operation time(t=-3.987,P<0.01),less bleeding(Z=-4.862,P<0.01),shorter total(Z=-5.009,P<0.01) and postoperative(Z=-5.412,P<0.01) hospital stay. Seventeen patients had postoperative complications. According to the Clavien-Dindo system,there were 4,11,1,and 1 patient with grade Ⅰ,Ⅱ,Ⅲa,and Ⅲb,respectively. All complications were improved after active treatment. After a median follow-up of 24(36) months(range:3 to 130 months),56 patients(58.3%) survived without tumor,7 patients(7.3%) survived with tumor,and 33 patients(34.4%) died. According to the Kaplan-Meier curves,there was no significant difference between laparoscopic and open groups in disease free(χ2=0.399,P=0.528) and overall(χ2=0.672,P=0.412) survival rates. Conclusions: The laparoscopic surgery is safe and effective in selected patients with gallbladder carcinoma. It can reduce surgical trauma and enhance patient recovery without increasing complication. Its prognosis is similar to that of open surgery.

[Application of enhanced recovery after surgery in perioperative management of patients with gallbladder carcinoma].

Objective: To investigate the efficacy and safety of enhanced recovery after surgery (ERAS) in perioperative management of patients with gallbladder carcinoma. Methods: The data of the patients with gallbladder carcinoma admitted at Peking Union Medical College Hospital between January 2017 and December 2021 were analyzed retrospectively. There were 69 males(42.1%) and 95 females(57.9%),with age of (64.0±10.3) years(range:37 to 89 years). Patients were divided into ERAS group(n=53) and normal group(n=111) according to whether they were treated with ERAS measures during the perioperative period.The basic characteristics of the two groups were matched by propensity score matching,and then the perioperative information was compared between the two groups. Categorical variables were presented as absolute numbers or frequencies. Differences between study groups were analyzed using χ2 test, Fisher's exact test, t-test, or Mann-Whitney U test, as appropriate. Results: Each group had 45 patients after propensity score matching with well-balanced basic characteristics. There was no difference in basic characteristics, operation time,bleeding,complication,and hospitalization expenses between two groups(all P>0.05). Compared with the normal group,time of ambulation (M(IQR)) (1(1) day vs. 2(2) days;Z=-3.839,P<0.01),postoperative anal exhaust time (2(1) days vs. 3(1) days;Z=-3.013,P=0.003),feeding time(2(1) days vs. 2(1) days;Z=-3.647,P<0.01),postoperative (5(2) days vs. 7(4) days;Z=-3.984,P<0.01) and total(8(4) days vs. 13(6) days;Z=-3.605,P<0.01) hospitalization time were shorter in ERAS group. Postoperative complications occurred in 12 patients. According to the Clavien-Dindo classification,6,4,and 2 patients were classified as grade Ⅰ,Ⅱ,and Ⅲa,respectively. Conclusion: The ERAS measures is safe and effective for perioperative management of patients with gallbladder carcinoma, enhancing patient recovery and shortening hospitalization time without increasing complication or hospitalization cost.

Effect of exosomes derived from mir-126-modified mesenchymal stem cells on the repair process of spinal cord injury in rats.

The article "Effect of exosomes derived from mir-126-modified mesenchymal stem cells on the repair process of spinal cord injury in rats, by B. Yuan, S. Pan, Y.-Q. Dong, W.-W. Zhang, X.-D. He, published in Eur Rev Med Pharmacol Sci 2020; 24(2):483-490. DOI: 10.26355/eurrev_202001_20025. PMID: 32016949" has been withdrawn from the publisher for plagiarism. The Publisher apologizes for any inconvenience this may cause.

[Clinical study on factor â § inhibitor in children with hemophilia A].

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.

Effect of exosomes derived from mir-126-modified mesenchymal stem cells on the repair process of spinal cord injury in rats.

OBJECTIVE: To investigate the effect of the micro ribonucleic acid (miR)-126-modified mesenchymal stem cell (MSC)-derived exosomes (MSC-exos) on the repair process of spinal cord injury (SCI) in rats. MATERIALS AND METHODS: MiR-126-modified MSCs were cultured, the exosomes were extracted, and a rat model of SCI was established. The Quantitative Polymerase Chain Reaction (qPCR) was carried out to detect the expression of miR-126 in the injured spinal cord, and the Western blotting (WB) was adopted to detect the expressions of the exosome-related molecules. Subsequently, the motor function recovery of rats was examined via the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. The effects of miR-126 exosomes on the injury volume and NeuN retention following SCI were evaluated via immunohistochemistry. RESULTS: MSCs were able to package miR-126 into exosomes secreted. After SCI, the recovery of the hind limb function of rats was remarkably improved by miR-126-modified MSC-exos relative to the control group. Treatment with miR-126-modified MSC-exos remarkably decreased the injury volume, retained the neuronal cells, and triggered the axon regeneration following SCI. Besides, the expression of Ras homolog gene family member A (RhoA), identified as the downstream gene of miR-126, was downregulated in the group with miR-126-modified MSC-exos. Moreover, miR-126-modified MSC-exos activated the extracellular regulated protein kinases 1/2 (ERK1/2) pathway. CONCLUSIONS: MiR-126-modified MSC-exos protect neurons of rats with SCI, stimulates axon regeneration, and improves the recovery of limb motor function after SCI.

[Metrological Analysis of the Projects in the Field of Forensic Science Funded by the National Natural Science Foundation of China between 2000 and 2019].

ABSTRACT: Objective To understand the trend of funding in the field of forensic science by analyzing the projects funded by the National Natural Science Foundation of China （NSFC）. Methods Based on the data of funded projects in the field of forensic science published on NSFC website in the twenty years from 2000 to 2019, the trend of project number and fund, project type, discipline type, funded institution and personnel were analyzed with metrological methods. The funding theme was analyzed through multi-methods. Results In the twenty years, NSFC funded 352 projects in the field of forensic science, including 9 project types, 47 institutions and 213 persons. General programs （184 projects）, forensic toxicology, pathology, and toxicology analysis （H2301, 188 projects）, and the Academy of Forensic Science （37 projects） had the most funded projects. NSFC funded 174.69 million yuan in the field of forensic science. The Excellent Young Scientists Fund （3.50 million yuan/project）, forensic toxicology, pathology, and toxicology analysis （H2301, 78.64 million yuan）, and Xi'an Jiaotong University （23.78 million yuan） had the most funding. The differences in the number and funding of subsidized projects between the first ten years and the last ten years had statistical significance （P<0.05）. The main targets of funding were toxicology research, evidence-related research, estimation-related research, brain injury research, et al. The field of research mainly funded from 2010 to 2019 was interdisciplinary research. Conclusion Since 2010, the number of project, funding of project, the number of institutions and persons funded by NSFC in the field of forensic science showed an increasing trend. The types of disciplines, types of projects and themes of projects are more diverse, which will promote the long-term development of basic forensic research in China.

Cloning and expression analysis of the follicle-stimulating hormone receptor (FSHR) gene in the reproductive axis of female yaks (Bos grunniens).

Follicle-stimulating hormone receptor (FSHR) plays a central role in promoting follicle maturation through the follicle-stimulating hormone (FSH)-mediated cAMP pathway in animals. The objectives of the present study were to clone the FSHR gene of yaks (Bos grunniens) and compare differences in FSHR mRNA expression in the reproductive axis between yaks and cattle. Hypothalamus, anterior pituitary, oviduct, ovary, and uterus tissue samples were collected from adult female yaks (n = 5) and cattle (n = 5) during the follicular phase. Using reverse transcriptase-polymerase chain reaction (RT-PCR), we found that the FSHR coding region of the yak is 2088 bp and encodes 695 amino acids. Its amino acid sequence showed 99.38%-72.22% similarity to the homologous genes of cattle, goats, sheep, cats, donkeys, horses, humans, chickens, monkeys, mice, rats, and wild boar. Real-time PCR analysis revealed that the FSHR gene was expressed in all tissues examined. Expression of the FSHR gene in the yak was higher in the uterus than other tissues (P < 0.05) but, in cattle, was higher in the ovary than other tissues (P < 0.05). The FSHR gene expression level in the cattle ovary was significantly higher than that in the yak ovary (P < 0.01). These results indicate that the FSHR gene is relatively conserved in the course of animal evolution. The variation in sequence and expression level of FSHR between the two species might be associated with the difference in their reproduction.

Evaluation and Countermeasures of the Implementation of Forensic Clinical Identification Standards Based on the Perspective of Accreditation.

ABSTRACT: The new Standardization Law, implemented in 2018, has added a standard post-implementation evaluation system, aiming to continuously improve the quality of standards through post-implementation evaluation. Standards in the forensic science field are closely related to accreditation activities. Forensic science standards are not only the criteria on which accreditation activities are carried out, but also one of the key contents of the inspection of forensic science institutions in accreditation activities. Since 2018, the certification and accreditation policies in the forensic science field have also been changed, which has brought impacts on the construction of a standard system based on accreditation.This paper analyzes the standard data from China National Accreditation Center from Conformity Assessment on forensic clinical identification accreditation assessment. It points out that the current coverage of laboratory accreditation activities is limited, the development in different provinces is unbalanced, and there is overlap and crossover in the standards in use. It is emphasized that the construction of the national forensic science standardization technical committee, the improvement of the forensic science standard system, the establishment of the standard implementation evaluation index system, and promotion of the coordination of standards, and the certifications and accreditations should be accelerated, in order to continue to promote the standardization and accreditation activities in the field of forensic science.

[Clinical characteristics of abdominal solitary fibrous tumor: an analysis of 18 cases].

Objective: To summarize the clinical manifestations, pathological features, diagnosis, and treatment of abdominal solitary fibrous tumor (SFT). Methods: The data of clinical manifestations, pathological features, diagnosis, and treatment of 18 patients with abdominal SFT admitted to Department of General Surgery, Peking Union Medical College Hospital between January 2000 and December 2016 were retrospectively reviewed. Results: Abdominal mass was first presented in 14 patients. The blood routine, liver, kidney, and coagulation function were normal in all the patients. Tumor markers were abnormal in 4 cases. Most SFT showed hypoechoic mass with regular shape under ultrasound. CT findings differed among the cases. All the 18 patients underwent surgical treatment, and the diagnosis was proved by the postoperative histopathology. SFT differed in general morphology. The positive rate of Ki-67, smooth muscle actin (SMA), CD34, and S-100 was high under immunohistochemistry. Conclusions: Early diagnosis of abdominal SFT is difficult, leading to a low preoperative diagnosis rate. Complete removal of the tumor is the only reliable method of radical treatment.

Long non-coding RNA LINC00628 suppresses the growth and metastasis and promotes cell apoptosis in breast cancer.

OBJECTIVE: Breast cancer is the most common malignant tumor in women. However, the detailed mechanisms of its tumorigenesis remain largely unknown. Evidence and data have shown that abnormality in expression of Long non-coding RNA (LncRNA) is closely related to tumorigenesis. The aim of this study is to identify the detailed mechanisms of LncRNA LINC00628 in breast cancer. PATIENTS AND METHODS: The expression of LINC00628 in breast cancer tissues, adjacent non-cancerous tissues and cell lines were detected by qRT-PCR. Kaplan-Meier method and log-rank test were applied to analyze the overall survival of patients with low and high expression level of LINC00628 respectively. The LCC2 and MCF-7 cells were transfected with LINC00628 and the proliferation, invasion and migration were examined. The cell cycle distribution and cell apoptosis rate in LCC2 and MCF-7 cells after transfection with LINC00628 were explored by flow cytometry. The relative expression level of Bcl-2, Bax and Caspase-3 protein in LCC2 and MCF-7 cells after transfection with LINC00628 was detected by Western blotting. RESULTS: The relative expression level of LINC00628 in breast cancer tissues and cell lines were significantly decreased and the low expression level of LINC00628 has a poorer prognosis and lower overall survival rate. The overexpression of LINC00628 suppressed breast cancer cells proliferation, invasion and migration. Further, with the overexpression of LINC00628, cell cycle was arrested in G0/G1 phase in breast cancer cells and cell apoptosis was promoted. The relative expression of Caspase-3 and Bax protein were significantly increased and the relative expression of Bcl-2 protein was significantly decreased after transfection with LINC00628. CONCLUSIONS: The expression of LINC00628 was decreased in breast cancer. The overexpression of LINC00628 suppressed the proliferation, invasion and migration of breast cancer cells and promoted cell apoptosis associated with the regulation of Bcl-2/Bax/Caspase-3 signal pathway.

[The efficiency of different biliary cannulation in endoscopic retrograde cholangiopancreatography: a meta-analysis].

Objective: To compare the success rates of wire-guided biliary cannulation (WGC) and conventional cannulation (CC) and their effect on the outcome of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Methods: All randomized controlled trials (RCTs) were collected by searching CNKI, WanFang Data, CBM, PubMed, Embase and Cochrane Library.The assessment of methodological quality and data extraction of the included studies were performed independently by two reviewers. Meta-analysis was conducted with RevMan 5.2 software. Results: Ten RCTs, with a total of 3 262 patients enrolled, were retrieved.Meta-analysis demonstrated that WGC had a higher success rate(RR=1.04, 95%CI 1.01-1.06, P<0.01)and a lower risk of PEP after cannulation (RR=0.54, 95%CI 0.41-0.71, P<0.01). The main reason for the lower risk of PEP was due to lower proportion of mild PEP patients after WGC(RR=0.52, 95%CI 0.36-0.73, P<0.01), while the incidence of modest and severe PEP was comparable in the two groups(modest group: RR=0.84, 95%CI 0.43-1.64, P=0.61; severe group: RR=0.53, 95%CI 0.22-1.31, P=0.17). Conclusion: WGC may increase the success rate of cannulation and reduce the incidence of PEP because of less complications of mild PEP.

Prognostic factors for the recurrence of sporadic desmoid-type fibromatosis after macroscopically complete resection: Analysis of 114 patients at a single institution.

AIMS: Desmoid-type fibromatoses (DFs) are rare soft-tissue neoplasms with frequent local recurrence. We sought to determine the prognostic factors that are predictive of recurrence-free survival (RFS) for these tumors. METHODS: One hundred and fourteen consecutive patients with sporadic DF who received macroscopically complete resection (R0/R1) at a single tertiary hospital between 1985 and 2014 were included. A total of 10 clinical and pathological parameters were analyzed. Histologic slides and the margin status were re-checked; close margins (≤1-mm clearance) were noted separately and were considered together with the R1 margin. RESULTS: The median follow-up interval was 72.5 months. Thirty-five (30.7%) patients had a local recurrence. The 2-, 5- and 10-year RFSs were 75.2%, 72.1% and 67.0%, respectively. In univariate analysis, age, tumor size, tumor site, margin status and presence of lesions at multiple sites had a significant impact on RFS. In multiple analysis, younger age (age<30 vs. age≥50 years: hazard ratio [HR] = 4.96; 95% confidence interval [95% CI], 1.50-16.4; p = 0.009); an extra-abdominal site (extra-abdominal site vs. other sites: HR = 4.08; 95% CI, 1.49-11.2; p = 0.006); larger tumor size (≥8 cm vs. <8 cm: HR = 2.43; 95% CI, 1.15-5.13; p = 0.021); and close or positive margin status (close margin/R1 vs. R0: HR = 2.64; 95% CI, 1.11-6.25; p = 0.027) were independent, unfavorable prognostic factors. CONCLUSIONS: Different prognostic subgroups were identified that allow for the better selection of favorable therapeutic strategies. The role of the margin status should be considered with caution and should be based on a more precise pathological result.

Bioinformatic analysis of endothelial progenitor cells exposed to folic acid in type 1 diabetes mellitus.

We investigated the effects of type 1 diabetes mellitus (T1DM) on endothelial progenitor cells (EPCs) at the molecular level and assessed the therapeutic potential of folic acid (FA) in DM. We downloaded the gene expression profile of the EPCs from T1DM patients before and after treatment with FA and from healthy controls. We identified the differentially expressed genes (DEGs) in the EPCs from T1DM patients before and after a four-week period of FA treatment and compared them with those obtained from the healthy subjects by using limma package in R language. Then, functional annotation of the DEGs was performed using the online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) based on the Kyoto Encyclopedia of Genes and Genomes database. The expression of 696 genes was altered in the EPCs from T1DM patients compared to those from the healthy controls. These genes were mainly involved in the pathways associated with immune response. FA can normalize majority of the altered gene expression profiles of EPCs from T1DM patients to resemble those of healthy subjects, albeit with some side effects. FA can be a potential therapeutic agent for the treatment of T1DM. However, focused efforts are required to ensure that the dose of FA falls within the permissible pharmacological range.

The structure and roles of sterile flowers in Viburnum macrocephalum f. keteleeri (Adoxaceae).

The formation and ecological roles of sterile flowers in flowering plants are interesting issues in floral biology and evolution. Here, we investigated the morphological and anatomical characteristics of both fertile and sterile flowers of Viburnum macrocephalum f. keteleeri, a self-incompatible and insect-pollinated shrub, during different developmental stages of flowers. In addition, pollinator visitation rates and fruit set were determined in intact inflorescences and those with sterile flowers removed. The results indicate that sterile and fertile flowers were developmentally similar during early developmental stages, and that development of the flower types diverged about 15 days before flowering. In addition, pollinator visitation rates, number of pollen grains on stigmas and fruit set were significantly higher in inflorescences with sterile flowers than those without sterile flowers. The results suggest that sterile flowers of this species evolved from fertile flowers under long-term selective pressure, and play a crucial role in enhancing reproductive success through effectively attracting pollinators to the plant and thus enhancing fruit set.

Neural and anatomical abnormalities of the gastrointestinal system resulting from contusion spinal cord injury.

Gastrointestinal (GI) abnormalities resulting from spinal cord injury (SCI) are challenging disorders that have not been examined experimentally using clinically relevant models. In this study, female Sprague-Dawley rats (n=5/groupx4: T10-T11 contusion, laminectomy, or naïve) were fasted for 24 h before being submitted to dye recovery assays (Phenol Red solution, 1.5 ml/rat; per oral) on GI emptying/transiting at 48 h or 4 weeks postinjury (p.i.). Compared with controls, SCI significantly increased dye recovery rate (DRR, determined by spectrophotometry) in the duodenum (+84.6%) and stomach (+32.6%), but decreased it in the jejunum (-64.1% and -49.5%) and ileum (-73.6% and -70.1%) at 48 h and 4 weeks p.i., respectively (P

Breast conservation therapy for stage I or stage II breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: We carried out a meta-analysis to determine the effectiveness of breast conservation therapy (BCT) or mastectomy (MT) for stage I or stage II breast cancer. METHODS: A fully recursive literature search was conducted in the Cochrane Controlled Trials Register Databases, Medline, EMBASE and Chinese Biomedical Literature Database in any language. Randomized controlled trials (RCTs) were considered for inclusion. Analyses were carried out using RevMan software. RESULTS: In all, 18 RCTs including a total of 9388 patients were included. The meta-analysis showed that the overall survival in 3, 5, 10, 15 and 20 years and the locoregional recurrence rate in 3, 5, 15 and 20 years were not statistically significantly different between group BCT and group MT, but 10-year locoregional recurrence rate increased in group BCT. The sensitivity analysis indicated that both overall survival and locoregional recurrence rate were not statistically significant difference between group BCT and group MT. In the subgroup analysis, there was no significant difference in OS and locoregional recurrence rate between group BCT and group MT, but 20-year locoregional recurrence rate was statistically significantly higher in group BCT than group MT for women with tumors 2 cm or smaller. CONCLUSION: BCT was better choice than MT for women with stage I or stage II breast cancer.

Role of HERG-like K(+) currents in opossum esophageal circular smooth muscle.

An inwardly rectifying K(+) conductance closely resembling the human ether-a-go-go-related gene (HERG) current was identified in single smooth muscle cells of opossum esophageal circular muscle. When cells were voltage clamped at 0 mV, in isotonic K(+) solution (140 mM), step hyperpolarizations to -120 mV in 10-mV increments resulted in large inward currents that activated rapidly and then declined slowly (inactivated) during the test pulse in a time- and voltage- dependent fashion. The HERG K(+) channel blockers E-4031 (1 microM), cisapride (1 microM), and La(3+) (100 microM) strongly inhibited these currents as did millimolar concentrations of Ba(2+). Immunoflourescence staining with anti-HERG antibody in single cells resulted in punctate staining at the sarcolemma. At membrane potentials near the resting membrane potential (-50 to -70 mV), this K(+) conductance did not inactivate completely. In conventional microelectrode recordings, both E-4031 and cisapride depolarized tissue strips by 10 mV and also induced phasic contractions. In combination, these results provide direct experimental evidence for expression of HERG-like K(+) currents in gastrointestinal smooth muscle cells and suggest that HERG plays an important role in modulating the resting membrane potential.

Monochloramine directly modulates Ca(2+)-activated K(+) channels in rabbit colonic muscularis mucosae.

BACKGROUND & AIMS: Mesenteric ischemia, infection, and inflammatory bowel disease may eventuate in severe colitis, complicated by toxic megacolon with impending intestinal perforation. Monochloramine (NH(2)Cl) is a membrane-permeant oxidant generated during colitis by the large amount of ambient luminal NH(3) in the colon. Reactive oxygen metabolites can modulate smooth muscle ion channels and thereby affect colonic motility, which is markedly impaired in colitis. METHODS: Effects of NH(2)Cl on ionic currents in the innermost smooth muscle layer of the colon, the tunica muscularis mucosae, were examined using the patch clamp technique. Membrane potential in whole tissue strips was measured using high-resistance microelectrodes. RESULTS: Whole cell voltage clamp experiments showed that NH(2)Cl (3-30 micromol/L) enhanced outward currents in a dose-dependent manner, increasing currents more than 8-fold at a test potential of +30 mV. Tail current analysis showed that the currents enhanced by NH(2)Cl were K(+) currents. Inhibition by tetraethylammonium and iberiotoxin suggested that these currents represented activation of large-conductance, Ca(2+)-activated K(+) channels. The membrane-impermeant oxidant taurine monochloramine, however, had no effect on whole cell currents. Single-channel studies in inside-out patches showed that NH(2)Cl increased open probability of a 257-pS channel in symmetrical (140 mmol/L) K(+). In the presence of NH(2)Cl, the steady-state voltage dependence of activation was shifted by -22 mV to the left with no change in the single-channel amplitude. The sulfhydryl alkylating agent N-ethylmaleimide prevented NH(2)Cl-induced channel activation. NH(2)Cl also hyperpolarized intact muscle strips, an effect blocked by iberiotoxin. CONCLUSIONS: NH(2)Cl, at concentrations expected to be found during colitis, may contribute to smooth muscle dysfunction by a direct oxidant effect on maxi K(+) channels.

Substance P inhibits pancreatic exocrine secretion via a neural mechanism.

We investigated the effects of the sensory neuropeptide substance P (SP) on amylase and fluid secretion in the isolated vascularly perfused rat pancreas. SP inhibited CCK-induced amylase release and secretin-induced juice flow via the pancreatic duct in a dose-related fashion. Threshold inhibition occurred following addition of 10(-10) M SP to the perfusate, and maximal inhibition was seen with 10(-8) M SP. The effects of SP were partially blocked by both the neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonists. Atropine and TTX blocked SP-induced effects on both amylase secretion (26 and 63% blockade, respectively) and pancreatic juice flow (21 and 79% blockade, respectively). Excitation of pancreatic sensory nerves using capsaicin (in the absence of SP) inhibited both amylase and pancreatic juice flow via activation of the NK1 receptor. We conclude that SP inhibits exocrine secretion via an indirect neural mechanism.

Evidence for NO. redox form of nitric oxide as nitrergic inhibitory neurotransmitter in gut.

A nitric oxide (NO)-like product of the L-arginine NO synthase pathway has been shown to be a major inhibitory neurotransmitter that is involved in the slow component of the inhibitory junction potential (IJP) elicited by stimulation of nonadrenergic, noncholinergic nerves. However, the exact nature of the nitrergic transmitter, the role of cGMP, and the involvement of a potassium or a chloride conductance in the slow IJP remain unresolved. We examined the effects of soluble guanylate cyclase inhibitors LY-83583 and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), potassium-channel blockers and putative chloride-channel blockers diphenylamine-2-carboxylate (DPC) and niflumic acid (NFA) on the hyperpolarization elicited by an NO. donor, diethylenetriamine/NO adduct (DNO), NO in solution, and an NO+ donor, sodium nitroprusside (SNP), in the guinea pig ileal circular muscle. Effects of these blockers on purinergic (fast) and nitrergic (slow) IJP were also examined. DNO-induced hyperpolarization and nitrergic slow IJP were suppressed by LY-83583 or ODQ and DPC or NFA but not by the potassium-channel blocker apamin. In contrast, hyperpolarization caused by SNP or solubilized NO gas and purinergic fast IJP were antagonized by apamin but not by inhibitors of guanylate cyclase or chloride channels. These results demonstrate biological differences in the actions of different redox states of NO and suggest that NO. is the nitrergic inhibitory neurotransmitter.