Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric artery

Background and Purpose

Previous studies have demonstrated that nicotine releases protons from adrenergic nerves via stimulation of nicotinic ACh receptors and activates transient receptor potential vanilloid-1 (TRPV1) receptors located on calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves, resulting in vasodilatation. The present study investigated whether perivascular nerves release protons, which modulate axon-axonal neurotransmission.

Experiment Approach

Perfusion pressure and pH levels of perfusate in rat-perfused mesenteric vascular beds without endothelium were measured with a pressure transducer and a pH meter respectively.

Key Results

Periarterial nerve stimulation (PNS) initially induced vasoconstriction, which was followed by long-lasting vasodilatation and decreased pH levels in the perfusate. Cold-storage denervation of the preparation abolished the decreased pH and vascular responses to PNS. The adrenergic neuron blocker guanethidine inhibited PNS-induced vasoconstriction and effects on pH, but not PNS-induced vasodilatation. Capsaicin (CGRP depletor), capsazepine and ruthenium red (TRPV1 inhibitors) attenuated the PNS-induced decrease in pH and vasodilatation. In denuded preparations, ACh caused long-lasting vasodilatation and lowered pH; these effects were inhibited by capsaicin pretreatment and atropine, but not by guanethidine or mecamylamine. Capsaicin injection induced vasodilatation and a reduction in pH, which were abolished by ruthenium red. The use of a fluorescent pH indicator demonstrated that application of nicotine, ACh and capsaicin outside small mesenteric arteries reduced perivascular pH levels and these effects were abolished in a Ca²⁺-free medium.

Conclusion and Implication

These results suggest that protons are released from perivascular adrenergic and CGRPergic nerves upon PNS and these protons modulate transmission in CGRPergic nerves.Tables of Links

The effect of casein phosphopeptide toothpaste versus fluoride toothpaste on remineralization of primary teeth enamel

This study evaluated the effect of a CPP-containing toothpaste and compared it with fluoride-containing toothpastes on remineralization of caries-like lesions in primary teeth enamel, using polarized light microscopy. Forty-eight sound primary incisors were coated with nail varnish, leaving two 1x1 mm windows before being placed in a demineralizing solution for 4 days. After demineralization, all the specimens were coated with nail varnish over one window and were randomly assigned to 4 groups (A to D; n = 12). Group A teeth were exposed to distilled water. Group B teeth were exposed to a CPP-containing toothpaste (Hi Herb). Group C teeth were exposed to a 260 ppm fluoride-containing toothpaste (Smile baby toothgel). Group D teeth were exposed to a 500 ppm fluoride-containing toothpaste (Oralmed Kid). Polarized light microscopy was used to evaluate lesion depth, before and after a 7-day pH cycle. Lesion depth was measured using a computerized method with the Image-Pro Plus program. Differences in mean lesion depth within groups and between groups were analysed using the paired t-test, Kruskal-Wallis test and Mann-Whitney U test at a 95% level of confidence. Mean lesion depths in Groups A, B, C and D significantly increased by 110.1, 36.1, 40.2 and 18.2%, respectively. The mean lesion depths for all the toothpaste groups (B, C and D) were significantly different from the control group (A). Comparisons made among treatment groups showed Group D was significantly different from Groups B and C. All toothpastes were effective for inhibiting progression of carious lesions. However, a 500 ppm fluoride-containing toothpaste inhibited lesion progression better than a CPP-containing toothpaste and a 260 ppm fluoride-containing toothpaste.     

State-art: diagnosis and management in pancreas divisum

Pancreas divisum (PD), the most common congenital variant of pancreatic duct anatomy, occurs when the ductal systems of the ventral and dorsal pancreatic ducts fail to fuse during the second month of gestation. With non-union of the ducts, the major portion of the pancreatic exocrine secretion enters the duodenum by way of the dorsal duct and minor papilla. It has been generally accepted that a relative obstruction to pancreatic exocrine secretory flow through the minor duct and minor papilla could result in pancreatitis in small numbers of patients with PD. The debate whether PD causes pancreatitis continues, although most authorities agree that PD is a definite cause in a subgroup of patients. Most patients with PD and well-documented acute recurrent pancreatitis have responded favorably to surgical sphincteroplasty of the minor papilla. Endoscopic retrograde cholangiopancreatography (ERCP) is the most common procedure for diagnosis PD in patients who have pancreatobiliary symptoms. MRCP is being increasingly used to establish the diagnosis and secretin stimulation can improve ductal images greatly. Endoscopic management of symptomatic patients with PD is evolving. Only a limited number of series are available, using endoscopic pancreatic stent placement, minor papilla endoscopic papillotomy, or both to decompress the dorsal duct in an effort to restore pancreatic exocrine secretory flow. Even with relatively small numbers of patients and a near absence of controlled, randomized trials, it appears that the patients most likely to benefit, as with surgery, are those with well-documented ARP rather than pain alone or chronic pancreatitis. Overall we recommend that pancreatic stenting and pancreatic sphincterotomy should be done only in large centers with experience in therapeutic ERCP. Further randomized trials would be of interest.     

Histamine H(3) receptor-mediated modulation of perivascular nerve transmission in rat mesenteric arteries

The rat mesenteric artery has been shown to be innervated by adrenergic vasoconstrictor nerves and calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves. The present study was designed to investigate the involvement of histamine H(3) receptors in the neurotransmission of perivascular adrenergic and CGRPergic nerves. The mesenteric vascular beds without an endothelium isolated from male Wistar rats were perfused with Krebs solution and perfusion pressure was measured. In preparations with resting tension, the selective H(3) receptor agonist (R)-α-methylhistamine (α-methylhistamine; 10-100nM) significantly reduced periarterial nerve stimulation (2-8Hz)-induced vasoconstriction and noradrenaline release in the perfusate without an effect on the vasoconstriction induced by exogenously injected noradrenaline (0.5, 1.0nmol). In preparations with active tone produced by methoxamine (2μM) and in the presence of guanethidine (5μM), the periarterial nerve stimulation (1, 2Hz)-induced vasodilator response was inhibited by α-methylhistamine (0.1-1μM) perfusion without affecting vasodilation induced by exogenously injected CGRP (5pmol). Clobenpropit (histamine H(3) receptor antagonist, 1μM) canceled the α-methylhistamine-induced decrease in the periarterial nerve stimulation-induced vasoconstriction and noradrenaline release and periarterial nerve stimulation-induced vasodilation. These results suggest that the stimulation of H(3) receptors located in rat perivascular nerves inhibits presynaptically the neurotransmission of not only adrenergic nerves, but also CGRP nerves, by decreasing neurotransmitters.     

A 6-month comparison of toothbrushing efficacy between the horizontal Scrub and modified Bass methods in visually impaired students

International Journal of Paediatric Dentistry 2011; 21: 278–283 Objective. The aim of this study was to compare the efficacy of the horizontal Scrub and modified Bass methods of toothbrushing in visually impaired students for 6 months. Methods. Sixty visually impaired students, aged 10–12 years, were recruited to a randomized controlled clinical trial. At baseline, plaque index (PI) and gingival index (GI) were assessed, and then subjects were randomly divided into the horizontal Scrub and modified Bass groups. Subjects received verbal and tactile toothbrushing instruction and used their assigned methods twice daily. They were recalled at 1 and 6 months for clinical measurement and reinforce of instruction. Significance of PI and GI over time was compared using the paired t‐test and between brushing group at each time point using the t‐test. Results. Over the 6‐month period, there were significant reduction from baseline for the mean PI and GI in both groups (P < 0.001). There were no significant differences between two methods at each time point (P > 0.05), however. Conclusions. Both the horizontal Scrub and modified Bass methods can be effectively reduced plaque index and gingival index in visually impaired students. The efficacy of both methods was not different, however.     

Involvement of perivascular nerves and transient receptor potential vanilloid 1 (TRPV1) in vascular responses to histamine in rat mesenteric resistance arteries

A previous report showed that histamine in denuded mesenteric vascular beds produced a triphasic response; an initial small histamine H(2) receptor-mediated vasodilation, a transient histamine H(1) receptor-mediated vasoconstriction, and finally a long-lasting vasodilation. We further investigated the vascular effect of histamine in mesenteric preparations without an endothelium to clarify the possible involvement of perivascular nerves. Male Wistar rat mesenteric vascular beds without an endothelium were perfused with Krebs solution containing methoxamine to produce active tone and lafutidine to block histamine H(2) receptor-mediated vasodilation. Histamine (1-100μM) was perfused for 1min and perfusion pressure was measured with a pressure transducer. Histamine caused a biphasic vascular response; initial vasoconstriction followed vasodilation. Tetrodotoxin (a neurotoxin, 1μM) and procaine (a local anesthetic, 100μM) significantly inhibited the vasoconstriction and vasodilation. Ruthenium red (a transient receptor potential vanilloid 1 (TRPV1) antagonist, 1μM) also significantly inhibited both phases of the response. Pretreatment with capsaicin (a depletor of calcitonin gene-related peptide (CGRP)-containing nerves, 5μM) significantly inhibited the vasodilation without affecting the initial vasoconstriction. Both indomethacin (a cyclooxygenase inhibitor, 0.5μM) and seratrodast (a thromboxane A(2) receptor antagonist, 0.1μM) abolished the histamine-induced vasoconstriction and subsequent vasodilation. These results suggest that histamine-induced vasoconstriction and long-lasting vasodilation are mediated by activation of TRPV1 on capsaicin-sensitive and capsaicin-insensitive nerves. They also suggest that perivascular nerves and prostanoids, probably thromboxane A(2), are responsible for the vascular response to histamine.     

Influence of pouch and stoma size on weight loss after gastric bypass

BackgroundEnlargement of the gastric pouch and/or gastrojejunostomy after Roux-en-Y gastric bypass (RYGB) is postulated to be the antecedent to suboptimal weight loss or weight regain. The present study evaluated the gastric pouch and stoma dimensions in RYGB patients and correlated them with the weight loss outcomes.MethodsPatients who underwent upper endoscopy for investigation of gastrointestinal symptoms or weight regain after RYGB were identified. The stoma was considered enlarged if >2 cm in diameter and the pouch was considered enlarged if >6 cm long or >5 cm wide. Successful weight loss was defined as excess weight loss >50% or a body mass index decrease to ≤30 kg/m².ResultsA total of 380 patients had nondiagnostic upper endoscopy findings at a mean post-RYGB interval of 5.9 ± 4.0 years. Among these were 175 patients (group A; 87% women) who had successful weight loss and 205 patients (group B; 86% women) who were referred for investigation of weight regain. The pouch and stoma size were normal in most of the patients in group A (63.4%) compared with 28.8% of the patients in group B (P <.001). The most common abnormality was an enlarged stoma. The pouch length, pouch volume, and stoma diameter correlated inversely with excess weight loss. Multivariate analysis identified that the stoma diameter was independently associated with weight regain after RYGB.ConclusionThe current definition of a “normal” size pouch/stoma is associated with optimal weight loss after RYGB, although this might need to be reviewed. Patients who regain weight are likely to have abnormal anatomy, in particular, stoma enlargement. The surgical RYGB technique and methods of evaluating the gastric anatomy in RYGB patients need to be standardized, intraoperatively and postoperatively.     

Endoscopic findings and outcomes of revisional procedures for patients with weight recidivism after gastric bypass

Background  

Significant weight regain occurs for 10% to 20% of patients after Roux-en-Y gastric bypass (RYGB). Potential causative factors include anatomic abnormalities such as enlargement of the gastric pouch and gastrojejunostomy (GJ). This report describes endoscopic findings for patients referred for investigation of weight regain and presents the outcomes of revisional therapy for patients with abnormal anatomy.     

Droperidol, when used for sedation during ERCP, may prolong the QT interval

BACKGROUND: Droperidol is a known effective adjunctive agent for sedation/analgesia during endoscopic procedures, particularly in patients who are difficult to sedate with narcotics and benzodiazepines alone. However, the Food and Drug Administration (FDA) warning about potential droperidol-related fatal cardiac arrhythmias, issued in December 2001, led to concern about its safety in current clinical practice. OBJECTIVE: In this study, we evaluated the effects of droperidol on the Bazett's corrected QT interval (QTcB) administered to patients undergoing ERCP and frequency of cardiac arrhythmias. DESIGN: We retrospectively reviewed the medical records of patients who, at our institute, underwent ERCP while under sedation/analgesia and who received droperidol. Our protocol for patients who are considered to be candidates for droperidol use includes obtaining an ECG before and 1 to 3 hours after the procedure. RESULTS: From April 2002 to October 2004, 6292 ERCPs were performed, of which 3113 patients with normal baseline QTcB (2001 women, 1112 men) received droperidol. Mean dosages were 4.3 mg (range, 1.25-10 mg) in women and 4.5 mg (range, 1.25-13.75 mg) in men. A total of 233 patients (7.48%; 133 women, 100 men) developed QTcB prolongation. Mean increases of the QTcB above the upper limit of normal were 16 milliseconds in women (range, 1-194 milliseconds) and 22 milliseconds in men (range, 1-310 milliseconds). Of these, 15 patients (0.48%; 8 women, 7 men) had marked prolongation of the QTcB (defined QTcB, >500 milliseconds). No serious dysrhythmias occurred. CONCLUSIONS: Droperidol at usual doses during sedation/analgesia may precipitate QTcB prolongation above the normal range. However, no QT-related arrhythmias were noted in this study. Clinically significant cardiac events are probably rare with droperidol, despite documented QTcB effects. Baseline electrocardiogram for excluding patients with prolonged baseline QTcB and 1 to 3 hours afterward monitoring appears adequate when using droperidol. The study is still too small to detect very infrequent arrhythmia events.     

Successful management of gastrojejunal strictures after gastric bypass: is timing important?

BackgroundEndoscopic balloon dilation is an effective treatment of gastrojejunal (GJ) strictures after Roux-en-Y gastric bypass (RYGB), although its success might depend on the point at which they occur postoperatively. We hypothesized that “late” strictures (≥90 d after RYGB) might be less amenable to balloon dilations than “early” strictures occurring within 90 days postoperatively.MethodsA review of a prospectively maintained database at a bariatric center was conducted to identify all patients who underwent upper endoscopy (UE) for investigation of gastrointestinal symptoms after RYGB. Those who were diagnosed with a GJ anastomotic stricture at endoscopy were selected for additional evaluation. The patients were classified into 1 of 3 groups, according to the point at which they presented with stricture symptoms (group 1, 0–90 d after RYGB; group 2, 91–365 d after RYGB; and group 3, >1 yr after RYGB). All strictures were dilated using through-the-scope controlled radial expansion balloons.ResultsFrom July 2006 to July 2009, 929 RYGB procedures were performed in our bariatric unit. Our surgical endoscopy team performs approximately 1500 UE investigations annually. Most investigations were for preoperative assessment of bariatric patients; however, a proportion is indicated for the investigation of postoperative weight regain and complications of foregut surgery, as well as endoluminal surgery. In the present study period, 591 gastric bypass patients underwent UE for investigation of gastrointestinal symptoms postoperatively. In total, 72 patients were diagnosed with a symptomatic GJ anastomotic stricture and underwent balloon dilation. Almost two thirds (63.9%) of the dilations were performed within 90 days after RYGB; 98% of these “early” strictures resolved with dilation. In comparison, of the “late” strictures, only 61% (16 of 26 patients) resolved and 38.5% (n = 10) required revisional surgery for additional management.ConclusionEndoscopic balloon dilation is effective in treating early GJ strictures after RYGB. Late strictures are less amenable to endoscopic dilation and often require revisional surgery. Patients presenting with upper gastrointestinal symptoms after RYGB warrant early investigation with UE to investigate for a GJ stricture, which if present, should be promptly dilated.