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- Expression and possible role of IGF-IR in the mouse gastric myenteric plexus and smooth muscles. [JOURNAL ARTICLE]
- Acta Histochem 2014 Mar 12.
Insulin-like growth factor-I (IGF-I) and its receptor (IGF-IR) have tremendous trophic effects on the central, peripheral and enteric neurons. The loss of IGF-IR contributes to the development of diabetic gastroparesis. However, the nature and the function of the IGF-IR(+) cells in the gastric myenteric plexus remain unclear. In this study, anti-ChAT, anti-S100β or anti-c-KIT antibodies were used to co-label IGF-IR(+) cells and neurons, glial cells or interstitial cells of Cajal (ICCs), respectively. We also generated type 1 diabetic mice (DM) to explore the influence of impaired IGF-I/IGF-IR in the myenteric neurons. Results showed that IGF-IR was expressed in the epithelium, smooth muscles and myenteric plexi of the mouse stomach. Most of the IGF-IR(+) cells in the myenteric plexi were ChAT(+) cholinergic neurons, but not enteric glial cells and there were more IGF-IR(+) neurons and fibers in the gastric antrum than in the corpus. The IGF-IR(+)/ChAT(+) neurons and ICCs were closely juxtaposed, but distinctly distributed in the myenteric plexus, indicating a possible role for the IGF-IR(+)/ChAT(+) neurons in the mediation of gastric motility through ICCs. Moreover, the decrease of IGF-IR and cholinergic neurons in the myenteric plexi and smooth muscles of DM mice suggested that IGF-I/IGF-IR signaling might play a role in neuron survival and neurite outgrowth, as well as stem cell factor (SCF) production, which is required for the development of ICCs. Our results provide insights into the effects of IGF-I/IGF-IR signaling on the development of gastrointestinal motility disorders.
- Granisetron Transdermal System Improves Refractory Nausea and Vomiting in Gastroparesis. [JOURNAL ARTICLE]
- Dig Dis Sci 2014 Mar 11.
Symptoms of gastroparesis include nausea and vomiting, which can markedly diminish quality of life. Nausea and vomiting can also make treatment with oral antiemetics problematic.Our aim was to determine whether treatment-resistant nausea and vomiting in patients with gastroparesis improve after granisetron transdermal patch (GTP) therapy.In an open-label pilot study, patients with gastroparesis and symptoms of nausea and vomiting refractory to conventional treatment were treated with GTP. After 2 weeks, patients were asked to assess their therapeutic response using the Clinical Patient Grading Assessment Scale (CPGAS; +7 = completely better; 0 = no change; -7 = very considerably worse). Responders were defined as CPGAS score >0, non-responders as ≤0.Patients (n = 36) were treated with GTP. Of these 36 patients, one patient discontinued treatment due to the GTP not adhering to the skin. Of the remaining 35 patients, 18 improved, 15 remained the same, and two worsened. The average CPGAS score was +1.8 ± 0.4 (SEM) (P < 0.05 vs 0). Of the 18 patients with improvement, the average CPGAS score was +3.7 ± 0.3 (SEM), corresponding to "somewhat" to "moderately better" improvement in nausea/vomiting. Side effects occurred in nine patients: four developed constipation, three patients had skin rash, and two reported headaches.GTP was moderately effective in reducing refractory symptoms of nausea and/or vomiting from gastroparesis in 50 % of patients. Mild side effects were reported by 25 % of patients. GTP may be an effective treatment for nausea and vomiting in gastroparesis, and further study is warranted.
- Comparative analysis of bilirubin in correlation to ALB between nephrotic syndrome patients and postoperative gastroparesis syndrome patients. [JOURNAL ARTICLE]
- Genet Mol Res 2014 Feb 14; 13(AOP)
This study aimed to disclose the potential causality of low bilirubin in patients with nephrotic syndrome (NS). Correlation analysis was carried out on total bilirubin (TBIL) to serum albumin (ALB), Upr, and Umalb/cr for three groups in a case-control study. P < 0.001 was observed for TBIL, ALB, Umalb/cr, and Upr between the NS and CGN groups, and P values of 0.0001, 1.000, 0.0001, and 0.0001 were observed for TBIL, ALB, Umalb/cr, and Upr, respectively, between the postoperative gastroparesis (PGS) and CGN groups. The values of r and P in correlation to TBIL were 0.549 and 0.000 for ALB, -0.405 and 0.000 for Umalb/cr, and -0.448 and 0.000 for Upr in the NS group; -0.007 and 0.959 for ALB, 0.213 and 0.091 for Umalb/cr, and -0.082 and 0.519 for Upr in the PGS group; and 0.509 and 0.000 for ALB, -0.431 and 0.000 for Umalb/cr, and -0.362 and 0.002 for Upr in the CGN group. A probable causality is implied between the low level of blood bilirubin and its loss in urine in NS patients. This conclusion may provide a theoretical basis for the feasibility of therapies against oxidative stress in NS patients.
- No Direct Projection is Observed from the Substantia Nigra to the Dorsal Vagus Complex in the Rat. [JOURNAL ARTICLE]
- J Parkinsons Dis 2014 Mar 10.
Background: Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by degeneration of dopaminergic neurons in the substantia nigra (SN). Destruction of the SN can lead to gastric dyskinesis accompanied by decreased expression of choline acetyltransferase (ChAT) and increased expression of tyrosine hydroxylase (TH) in the dorsal vagus complex (DVC), which includes the dorsal motor nucleus of the vagus (DMV) and nucleus tractus solitarii (NTS). However, it is unclear if the SN and DVC are directly connected. Objective: To investigate the neural projection from the SN to the DVC in rats. Methods: Retrograde and anterograde tracing techniques combined with double-labeling immunofluorescence technique were used. Results: Destruction of the SN significantly decreases ChAT immunoreactivity (IR) and increases TH-IR in the DVC. After injection of the retrograde tracer fluoro-gold (FG) into the DVC, FG-labeled neurons were observed in the hypothalamic paraventricular nucleus (PVN), lateral hypothalamus (LH), inferior olive (IO), and locus coeruleus (LC). No FG-positive cells were observed in the SN or striatum. Furthermore, after injection of anterograde tracer biotinylated dextran amine (BDA) into the SN, BDA-positive fibers were observed in the caudate putamen (Cpu), globus pallidus (GP), LC, and LH but not in the DVC. Conclusion: This study is the first to demonstrate that neurons in the SN do not directly innervate the DVC in rats. The DVC might be indirectly innervated by the SN through the hypothalamus and/or the LC. These data provide important morphological insights into the potential mechanism underlying the gastroparesis observed in PD patients.
- The relationship between symptom improvement and gastric emptying in the treatment of gastroparesis: remember the pharmacology. [Comment, Letter]
- Am J Gastroenterol 2014 Mar; 109(3):444-5.
- Xiangshaliujunzi Decoction for the treatment of diabetic gastroparesis: a systematic review. [Journal Article, Research Support, Non-U.S. Gov't]
- World J Gastroenterol 2014 Jan 14; 20(2):561-8.
To assess the current clinical evidence of the effectiveness of Xiangshaliujunzi Decoction (XSLJZD) for the treatment of diabetic gastroparesis (DGP).Randomized controlled trials (RCTs) were retrieved from seven major electronic databases including Medline, the Cochrane Library, Embase, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP), and Wanfang Databases, using search dates from the beginning of the databases to May 2013. No language limitations were applied. We included RCTs that used XSLJZD or a modified XSLJZD compared with a control group for the treatment of DGP. The control groups included conventional treatment (Western medicinal treatment), placebo, and no treatment (blank), but not acupuncture. The main outcome index was clinical effectiveness, which was based on the gastric emptying test and variations in the gastrointestinal (GI) symptoms between the treatment and control groups after intervention. Data extraction, analysis, and quality assessment were conducted according to the Cochrane Handbook for Systematic Review of Interventions, Version 5.1.0.Ten RCTs involving 867 patients (441 in the experimental groups, and 426 in the control groups) were identified, and the overall methodological quality was evaluated as generally low. In the treatment groups, all 10 trials used herbs alone as the treatment, whereas all control groups used prokinetic medicine. The period of intervention ranged from 2 to 8 wk. Three classes were used to evaluate treatment efficacy: significant effective, effective, and ineffective, and all trials used the clinical effective rate (based on the gastric emptying test and changes in GI symptoms) to evaluate efficacy. The data showed that the effects of XSLJZD for the treatment of DGP were superior to the control group (n = 867, RR =1.33, 95%CI: 1.24-1.42, Z = 8.11, P < 0.00001). Two trials recorded adverse events, and one trial reported follow-up.XSLJZD could restore the gastric emptying rate and improve symptoms. However, the evidence remains weak due to the poor methodological quality of the included studies.
- Gender aspects suggestive of gastroparesis in patients with diabetes mellitus: a cross-sectional survey. [Journal Article]
- BMC Gastroenterol 2014.:34.
It is suggested that symptoms related to gastroparesis are more common in female than in male patients with type 2 diabetes mellitus (T2DM). The association between sex and prevalence of symptoms suggestive of gastroparesis among patients with T2DM in Israel has not been reported. The aim of this study was to describe the associations between sex, clinical characteristics, type, severity and prevalence of dyspeptic symptoms in a large population of patients with T2DM in Israel.All patients completed a demographic questionnaire and the Gastroparesis Cardinal Symptom Index (GCSI). Data regarding disease duration, medications, complications, recent blood glucose and HbA1c levels were also collected. In this nested case-control study, 173 female and 209 male patients were identified from within a cross-sectional survey of 382 patients with T2DM. Logistic and general linear modeling was used to assess associations between sex, clinical data, and the presence (type and number) of symptoms.Compared to males, female patients with T2DM had a higher body mass index (BMI) (31.9 vs. 29.2; P = 0.001) and HbA1c levels (7.9 vs. 7.5; P = 0.04). A larger proportion of males suffered from peripheral vascular disease (P = 0.02) and ischemic heart disease (P = 0.001). Other disease characteristics did not differ between the sexes. The prevalence of nausea (P = 0.001), early satiety (P = 0.005), loss of appetite (P = 0.002), or presence of any cardinal symptom (P = 0.001) was significantly higher among females. Severity of most cardinal symptoms was also higher in females. The presence of at least one cardinal symptom was more likely among obese females with longer disease duration and poor glycemic control.Prevalence and severity of symptoms suggestive of gastroparesis is particularly high among obese females with long standing and poorly controlled T2DM.
- Efficacy of laparoscopic pyloroplasty for the treatment of gastroparesis. [Journal Article]
- J Am Coll Surg 2014 Apr; 218(4):652-60.
The modest results of nonoperative modalities for the treatment of gastroparesis necessitate greater consideration of surgical therapies. However, the role of surgery is not well defined. The aim of this study is to present our experience with laparoscopic pyloroplasty as early treatment for gastroparesis.Fifty patients with refractory gastroparesis underwent laparoscopic pyloroplasty (hand-sewn Heineke-Mikulicz configuration) from 2006 to 2013 at our institution. Preoperative and postoperative symptom data, gastric emptying scintigraphy, and technical outcomes of the procedure were reviewed. A single-factor ANOVA was performed for the comparison of continuous variables. Results are reported as mean ± SD or median absolute deviation.Thirty-four of 50 (68%) patients had previous foregut procedures and/or cholecystectomy. Thirty-two of 50 (64%) patients underwent concomitant procedures (ie, paraesophageal hernia repair and gastrostomy takedown) along with the pyloroplasty. Operative time, including combined procedures, blood loss, and length of stay were 175 ± 56 minutes, 64 ± 50 mL, 2.5 ± 2.7 days, respectively. There were no conversions to open technique or intraoperative complications. There were no suture-line leaks. The readmission rate was 14%. All patients had symptom follow-up and 33 (66%) had postoperative gastric emptying scintigraphy. Postoperative symptom improvement was reported by 82% of the patients (p < 0.001). Median preoperative T1/2 was 180 ± 73 minutes and postoperative T1/2 was 60 ± 23 minutes (p < 0.001). Five patients (10%), who had normalized postoperative T1/2 times, required other gastric emptying procedures; distal gastrectomy (n = 2), duodenojejunostomy (n = 2), and gastric stimulator placement (n = 1).Laparoscopic pyloroplasty is an effective early-treatment modality for selected cases of gastroparesis, with substantial improvement in objective gastric emptying times and low morbidity. The laparoscopic approach does not preclude subsequent procedures when necessary.
- Myosin Va plays a role in nitrergic smooth muscle relaxation in gastric fundus and corpora cavernosa of penis. [Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.]
- PLoS One 2014; 9(2):e86778.
The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS) within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO) mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF) and penile corpus cavernosum (CCP) to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti) mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT) mice, electrical field stimulation (EFS) of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP), caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction.
- Malignancy-associated gastroparesis: an important and overlooked cause of chronic nausea and vomiting. [Journal Article]
- BMJ Case Rep 2014.
A 69-year-old woman was referred to a gastroenterology clinic with a 1-year history of protracted nausea and postprandial vomiting. She had a background of gastro-oesophageal reflux disease, irritable bowel syndrome and chronic obstructive pulmonary disease with a significant smoking history. Her laboratory work-up including autoimmune screen, coeliac serology and synacthen test were unremarkable. Upper gastrointestinalendoscopy and CT imaging ruled out mucosal and obstructive causes. Gastric emptying studies demonstrated a delayed gastric emptying consistent with diagnosis of gastroparesis. Concurrently, she underwent a CT of the thorax for unresolved consolidation on her chest X-ray. This revealed a locally advanced primary lung carcinoma. In this context, with all other causes excluded, her gastroparesis was deemed to represent a paraneoplastic phenomenon. Gastroparesis is a frequent, under-recognised and important complication of cancer.