Effect of EM574 on Postprandial Pancreaticobiliary Secretion, Gastric Motor Activity, and Emptying in Conscious Dogs

EM574, an erythromycin derivative and a potentmotilin receptor agonist, is now under clinical trial asa gastroprokinetic drug. The aim of this study was toestimate the effect of EM574 on postprandial pancreaticobiliary secretion, gastric motoractivity, and emptying in conscious dogs. Five mongreldogs were prepared. Indwelling cannulas for bothinfusion of phenolsulfonphthalein and aspiration ofluminal samples were inserted into the proximal anddistal duodenum, respectively. EM574 (3-30 g/kg) wasgiven intraduodenally through the indwelling distalduodenal cannula at the start of feeding. Postprandial pancreatic and biliary secretions were assessedby measuring the outputs of amylase and bile acid intothe duodenum, respectively. Gastric motor and emptyingactivity were measured by means of a force transducer method and our own freeze-drying method,respectively. One hundred grams of a freeze-driedstandard meal was given as a solid marker after beingmixed with 100 ml of normal saline containing 15 g ofpolyethylene glycol as a liquid marker. EM574 at doses of 10and 30 g/kg significantly increased the meanintegrated postprandial amylase output into theduodenum, but the mean integrated postprandial bile acidoutput was not significantly increased. EM574increased postprandial gastric antral motor activitydosedependently. EM574 at doses of 10 and 30 g/kgsignificantly accelerated gastric emptying of liquidsand solids, respectively. EM574 enhances gastricantral motor activity and accelerates gastric emptyingof solids and liquids with a concomitant increase inpostprandial pancreatic amylase, but not bile acid, output in normal dogs.     

Gastric Emptying of Liquids and Postprandial Pancreatobiliary Secretion are Temporarily Impaired During Endotoxemia

The aims of our study were to determinemechanisms by which pancreatobiliary secretion isaltered during endotoxemia. Dogs underwent placement ofduodenal perfusion and aspiration catheters and antralmanometry catheters. Gastric emptying of liquids, antralmotility, output of bile acids and amylase, and serumlevels of enteric hormones were determined afteringestion of a 360-kcal mixed-nutrient liquid meal. Each dog was then given a single dose of E.coli lipopolysaccharide (200 g/kg, intravenously)and the studies repeated for the next three days.Endotoxin slowed gastric emptying of liquids anddecreased amylase output for two days. Bile acid outputwas decreased on postendotoxin day 1. Pancreaticpolypeptide alone was decreased on postendotoxin day 1.We conclude that the decrease in pancreatobiliary output is probably due to decreased nutrient flow intothe duodenum and not due to decreased production ofhormones that influence pancreatobiliary secretion. Thedelayed gastric emptying, decreased pancreatobiliary output, and decreased postprandial levels ofpancreatic polypeptide suggest diminished vagal outputas a possible explanation for the effects of endotoxinon upper gut function.     

Gallbladder Volume (Comparison of Diabetics and Controls)

Diabetics are known to have an increasedprevalence of gallstones. The aim of this study was toinvestigate whether diabetics have increased gallbladdervolumes that would predispose to stasis, nucleation of cholesterol crystals, and gallstoneformation. The gallbladder volume of 271 diabeticsubjects and 277 controls was determined by ultrasoundusing the ellipse formula. Gallbladder volume was alsodetermined by the sum of the cylinders method in 143 caseswith a strong correlation (r = 0.89) between the twomethods. Using analysis of variance, gallbladder volumewas influenced by both diabetic type (NIDDM 33.68 cm³, IDDM = 26.84 cm³,controls 29.05 cm³; P = 0.018) and thepresence of gallstones (gallstones 32.04 cm³,no gallstones 27.58 cm³; P = 0.018). Thevariation in gallbladder volume between NIDDM, IDDM, andcontrol subjects was influenced by the presence ofgallstones (P = 0.024, interaction term from ANOVA).Significant differences (P < 0.001) were only foundbetween NIDDM vs IDDM and NIDDM vs control in thenongallstone group (NIDDM 34.33 cm³, IDDM = 25.08cm³, control = 25.17 cm³). Maleshad significantly larger gallbladder volumes thanfemales: 31.98 cm³ vs 27.74 cm³ (P= 0.023). After the inclusion of BMI, HDL cholesterol, triglyceride, and age in a statistical modelwith gender and diabetic type in those withoutgallstones, significant differences were still foundbetween NIDDM and IDDM (P = 0.013) and NIDDM andcontrols (P = 0.005), demonstrating that NIDDM is anindependent predictor for increased gallbladdervolume.     

B超测定胆囊排空率餐后测定时间的探讨

背景:B超检查是测定胆囊排空率的常用方法之一,目前胆囊排空率餐后测定时间选择的差异较大并影响到该方法的应用,探讨较理想的餐后测定时间将有益于临床实践。目的:探讨B超测定胆囊排空率的餐后测定时间。方法:对13例健康志愿者于空腹以及流质脂餐后30、60、90和120 min时用B超测定胆囊容积,计算并比较各时点的胆囊排空率。结果:13例健康志愿者餐后30 min时的胆囊排空率为55.0％±13.2％,与60、90和120 min时的排空率相比无显著差异（P>0.05）,但餐后30 min时数据的个体间变异系数最小。结论:B超测定胆囊排空率,餐后30 min时的测定值波动范围相对较小,能较客观地反映胆囊动力状态。     

Distal Small Bowel Hormones (Correlation with Fasting Antroduodenal Motility and Gastric Emptying)

The aim of the present study was to study theinterdigestive motor complex (MMC), distal smallintestinal hormones, and gastric emptying innormal-weight and obese subjects before and afterjejunoileal bypass (JIB). Therefore, fasting antroduodenalmotility, gastric emptying, and RIA for motilin (MOT),neurotensin (NT), peptide YY (PYY), and glucagon-likepeptide-1 (GLP-1) was performed in nine obese subjects before (BMI 42 ± 4kg/m²) and nine months after (BMI 31 ±4) JIB, and in two groups of nine age- and sex-matchedcontrols (BMI 23 ± 1 and 21 ± 1). The rateof gastric emptying was faster in obese subjects and GLP-1 lower compared to normal-weightcontrols. After JIB, fewer phase III of the MMC wereobserved; fasting levels of PYY were elevated during theMMC; postprandial levels of NT, PYY, and GLP-1 were elevated; and gastric emptying was delayed. Ourresults suggest that there may be an association betweenan impaired GLP-1 response after food intake andobesity, and after JIB, PYY seems to regulateinterdigestive motility while GLP-1 may regulate early gastricemptying.     

Assessment of Gastric Emptying (Comparison of Solid Scintigraphic Emptying and Emptying of Radiopaque Markers in Patients and Healthy Subjects)

The gold standard for measuring gastric emptyingis scintigraphy, either with digestible solids orliquids. Unfortunately, this method is expensive and oflimited availability. An alternative could be to use radiopaque markers (ROMs). Our aim was tocompare these two tests in healthy volunteers and inpatients to see whether emptying of ROMs can substitutefor scintigraphic solid emptying. We also intended to see if patients with small intestinalbacterial overgrowth (SIBO) had delayed gastricemptying. Twenty healthy subjects and 21 patients, 11with SIBO and 10 with insulin-dependent diabetesmellitus (IDDM), were included. A standard meal with a[^99mTc]MAA-labeled omelet and 20 ROMs wasgiven. Scintigraphic emptying and ROM emptying werefollowed simultaneously. Reference values for gastricemptying of ROMs were determined in 50 healthy subjects. Thescintigraphic method and the radiologic methodcorrelated significantly in healthy subjects (P <0.05), and in patients (P < 0.001), when comparinghalf-emptying time for both methods. Scintigraphichalf-emptying time correlated significantly withemptying of ROMs after 6 hr. Six of 11 patients withSIBO (P < 0.02) and 7/10 patients with IDDM (P <0.02) had delayed scintigraphic emptying of solids usingthe 95th percentile in the controls as the upperreference value. Gastric emptying of ROMs was, similarto solid scintigraphic gastric emptying, slower in women than in men. In conclusion, scintigraphicemptying of solids and emptying of ROMs are closelycorrelated. The radiologic method can be used as asimpler and more readily available method. Women have slower gastric emptying of ROMs than men, whichnecessitates separate reference values. A highproportion of patients with symptomatic IDDM and withSIBO have delayed gastric emptying.     

Gastric Emptying of Indigestible versus Digestible Oils and Solid Fats in Normal Humans

Recent scintigraphic studies indicate thatlipolytic products in the small intestine do not inhibitgastric emptying of fat as potently as previouslysuggested by studies that compared a liquid indigestible oil with a solid digestible fat. The olderstudies left open the confounding possibility that solidfats emptied differently than liquid oil. We studiedeight normal subjects who ingested four meals in which fat was (1) liquid, digestible Criscooil, (2) liquid, indigestible sucrose polyester oil, (3)digestible, solid Crisco, and (4) indigestible, solidolestra. Fats were labeled with iodine-123, and their gastric emptying was followed with agamma camera. Indigestible fats (whether liquid orsolid) emptied consistently faster than digestible fats(P < 0.005), although differences were small. Solid fats emptied about as rapidly as oils in thefirst hour; but more slowly thereafter (P < 0.01). Acomparison of present scintigraphic with older studiessuggested that solid fats were not well tracked by duodenal, marker-perfusion techniques, whichmisled previous investigators.     

Common Pathogenetic Mechanisms in Symptomatic, Uncomplicated Gallstone Disease and Functional Dyspepsia (Volume Measurement of Gallbladder and Antrum Using Three-Dimensional Ultrasonography)

Following cholecystectomy for uncomplicatedgallstone disease (GS) some patients experiencepersistent symptoms suggesting an underlying functionaldisorder. To study this phenomenon, we have comparedsymptomatic GS with functional dyspepsia (FD) patients andhealthy individuals (C) with respect to putativepathogenetic mechanisms. Gallbladder and gastric antrumvolumes were estimated with three-dimensional (3D) ultrasonography before and 10 min afteringestion of 500 ml meat soup in 18 patients with GS.Volume estimation was performed digitally afterinteractive manual tracing and organ reconstruction inthree dimensions. Respiratory sinus arrhythmia (RSA)was calculated to index vagal tone. Abdominal symptomswere assessed by interview. The results were compared topreviously published data in patients with FD and C investigated with the exact samemethods. No significant differences were found betweengroups with respect to fasting gallbladder orgallbladder emptying. Antral volumes both fasting (P< 0.05) and postprandially (P < 0.01) were larger inGS and FD than in C. The soup meal induced dyspepticsymptoms in 2/18 (11% ) of C, 12/18 (67% ) of GS and15/17 (88%) of FD patients (P < 0.001). Compared with C, both GS and FD patients had significantlydecreased vagal tone (P < 0.001). There was nosignificant difference between GS and FD patients withrespect to antral volume, vagal tone, or symptoms. Weconcluded that both gallstone and functional dyspepsiapatients are characterized by dyspeptic symptoms inresponse to ingestion of 500 ml of meat soup, a widegastric antrum, low vagal tone, but normal gallbladder size and emptying. Thus, patients withsymptomatic, uncomplicated gallstone disease andfunctional dyspepsia seem to have common pathogeneticmechanisms.     

Gallbladder Emptying and Gastrointestinal Cyclic Motor Activity in Humans

The purpose of the present work was to answer two questions: does the human gallbladder empty in the fasting state, and. if so, is the emptying related to a specific phase of the activity in the gastrointestinal tract? The material consisted of nine healthy volunteers and the motility recordings were done with a perfused low-compliance system. Gallbladder emptying was recorded by the use of scintigraphy with ^99mTc-HIDA®. Eleven activity fronts were observed, and seven periods of gallbladder emptying were recorded. Reduction in counts over the gallbladder ranged from 8% to 32%. All emptyings took place in connection with phase-II activity in the intestine. Three were in close proximity to the following phase-III activity, and the other four occurred early in a phase II. Four activity fronts were not accompanied by output of bile. Conclusions: bile output from the gallbladder occurs in fasting humans, and gallbladder emptying takes place in connection with phase-II activity in the intestine but not always in close connection with the following phase-III activity.     

Fasting,Postprandial and Postprandial plus Glucagon-stimulated Plasma C-peptide Levels in Non-insulin-dependent Diabetics and in Control Subjects

ABSTRACT. Sarlund H, Laakso M, PyÖrÄlÄ K, PenttilÄ I (Departments of Internal Medicine and Clinical Chemistry, Kuopio University Central Hospital, Kuopio, Finland). Fasting, postprandial and postprandial plus glucagon-stimulated plasma C-peptide levels in non-insulin-dependent diabetics and in control subjects. We have studied fasting, postprandial and postprandial plus glucagon-stimulated plasma C-peptide levels in 149 non-insulin-dependent diabetics treated either with diet or oral drugs and in 101 non-diabetic control subjects. Diet-treated diabetics showed the highest fasting, postprandial and post-glucagon C-peptide levels in both sexes. In men, diabetics treated with oral drugs showed lower postprandial and glucagon-stimulated C-peptide levels than control subjects, while in women C-peptide levels in this group of diabetics were similar to those in control subjects. The distribution of individual plasma C-peptide levels was wide in non-insulin-dependent diabetics and control subjects and there was considerable overlapping in plasma C-peptide distribution for diabetics and control subjects. Fasting and post-glucagon plasma C-peptide levels in diabetics showed an inverse association to plasma glucose levels and a positive association to degree of obesity, but no association with the known duration of diabetes.     

Central Effects of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) on Gastric Motility and Emptying in Rats

Pituitary adenylate cyclase activatingpolypeptide (PACAP) is a new member of thesecretinglucagon-vasoactive intestinal peptide (VIP)peptide family. PACAP is widely distributed not only inthe mammalian brain but also in the gastrointestinal tract.Here, we investigated the effects of central andperipheral administrations of PACAP on gastric motilityand gastric emptying in rats. We found that theintracerebroventricular or intracisternal injection of PACAP increasedgastric motility in a dose-dependent manner. Theintracisternal injection of PACAP delayed gastricemptying. These central effects of PACAP on gastricmotility and emptying were blocked by bilateralvagotomy. In contrast, intravenous administration ofPACAP decreased gastric motility and delayed gastricemptying. The peripheral inhibitory effect wasunaffected by bilateral vagotomy, adrenalectomy,phentolamine, and propranolol. We investigated theeffect of PACAP38 on blood glucose levels (BGL) at thesame doses as those used in the gastric motility andemptying studies in urethane-anesthetized rats. Theintravenous but not intracerebroventricular injection ofPACAP38 (1-8 nmol/rat) produced a significant increasein the BGL. We conclude that PACAP has opposite central and peripheral effects on gastricmotility, ie, central PACAP activates the vagal pathwayin the central nervous system to increase gastricmotility, whereas peripheral PACAP inhibits gastricmotility via an unknown pathway. The delay in gastricemptying after the central administration of PACAP mightbe due to the lack of coordinated gastropyloroduodenalcontraction, whereas that after the peripheral administration might be due to the inhibitionof gastric contraction, and this effect may be relatedto the hyperglycemic action of PACAP.     

Self-monitoring of Triglycerides by Type 2 Diabetic Patients: Variability in Fasting and Postprandial Levels

Triglycerides are an important risk factor for coronary heart disease in Type 2 (non-insulin-dependent) diabetes mellitus. Although Type 2 diabetic patients have an exaggerated postprandial triglyceride response to a fat meal test, little is known about the variability of triglyceride concentrations in day-to-day life. We have studied the variability in triglyceride concentrations in 24 Type 2 diabetic patients over 6 months by having them record fasting and postprandial triglyceride concentrations at home using a Reflotron dry chemistry analyser. All patients were able to use the analyser effectively, with a correlation of 0.97 between patients' monthly Reflotron readings and those recorded by the laboratory. Over 1600 measurements were performed. The results demonstrate a large variation in both fasting (median 1.95 mmol l⁻¹, range 0.8–6.7 mmol l⁻¹) and postprandial triglyceride concentrations (median 2.68 mmol l⁻¹, range 0.8–6.7 mmol l⁻¹). This variation was accounted for by both a large intra- and inter-individual variation. Although there was a strong correlation overall between fasting and postprandial triglyceride concentrations r = 0.925 (p < 0.001), this did not apply on an individual basis. In conclusion, the large variability in triglyceride concentrations should be considered before introducing pharmacological therapy for hypertriglyceridaemia in Type 2 diabetes mellitus.     

Dissolution of Gallbladder Stones with Methyl tert-Butyl Ether and Stone Recurrence (A European Survey)

Since there are now several ways to treatsymptomatic gallstone disease, one is able to selecttreatment on the basis of the patient's comfort, thepracticability, effectiveness, and side effects of the technique, and the relative costs. In order toassess the present status of contact dissolution withmethyl tert-butyl ether with regard to these aspects,the present enquiry reports the data of 21 European hospitals. Eight hundred three patients wereselected for contact litholysis of cholesterolgallbladder stones using methyl tert-butyl ether.Percutaneous transhepatic puncture of the gallbladderwas performed under x-ray or ultrasound guidance. Dissolutionrate, side effects, and treatment times of 268 patientsfrom one single center were compared to those of 535patients from the other 20 centers. Two hundred sixty-four patients were followed for fiveyears to assess stone recurrence. Physicians were askedhow they assessed the expenditure of the method, thediscomfort to the patients, and the staffing situation. Patients were asked to indicate theiracceptance on an analog scale. Puncture was successfulin 761 (94.8%) patients. Prophylactic administration ofantibiotics was not necessary. Stones were dissolved in 724 (95.1%) patients. In 315 (43.5%) sludgeremained in the gallbladder. The most severecomplication was bile leakage, which led 12 (1.6%)patients to have elective cholecystectomy. Toxicinjuries due to the ether were not reported.Methodrelated lethality amounted to 0%, 30-day-lethalityto 0.4%. Stone recurrence rate was about 40% in solitarystones and about 70% in multiple stones over five years. Patients with multiple stones developedrecurrent stones almost twice as often as those withsolitary stones. The probability of stone recurrence inpatients with sludge in the gallbladder after catheter removal was not statistically significantlydifferent from those without sludge. Seventy to 90% ofthe centers found the puncture to be simple and notdistressing for patients and the relation betweenexpenditure and therapeutic success to be acceptable. Theacceptance of contact litholysis by the patients wasexcellent. Contact litholysis when applied by anexperienced team provides real advantages in thetreatment of gallstone disease. The method is technicallysimple, well accepted by the patients, and can be easilyapplied in community hospitals. Contact litholysis maybe of particular value in patients who are not suitable for anesthesia orsurgery.     

Proximal and Overall Gastric Emptying of Solids in Patients with Reduced Gastric Volume Accommodation Compared to Matched Controls

Background  

Interventions such as gastric surgery and erythromycin result in displacement of solids to the distal stomach and acceleration of overall and proximal gastric emptying. The effect of non-surgical impairment of gastric accommodation on gastric emptying is unclear. Non-surgical impairment of gastric accommodation is associated with accelerated gastric emptying.     

Emerging Phage Resistance in Pseudomonas aeruginosa PAO1 Is Accompanied by an Enhanced Heterogeneity and Reduced Virulence

Bacterial surface structures of a proteinic nature and glycoconjugates contribute to biofilm formation and provide shields to host defense mechanisms (e.g., the complement system and phagocytosis). A loss or alteration of these molecules, leading to phage resistance, could result in fewer virulent bacteria. In this study, we evaluate the biology and phenotype changes in Pseudomonas aeruginosa PAO1 phage-resistant clones, which emerge in phage-treated biofilms. We characterize these clones for phage-typing patterns, antibiotic resistance, biofilm formation, pathogenicity, and interactions with the innate immune system. Another important question that we address is whether phage-resistant mutants are also generated incidentally, despite the phage treatment-selective pressure, as the natural adaptation of the living biofilm population. It is found that the application of different phages targeting a particular receptor selects similar phage resistance patterns. Nevertheless, this results in a dramatic increase in the population heterogeneity, giving over a dozen phage-typing patterns, compared to one of the untreated PAO1 sessile forms. We also confirm the hypothesis that “phage-resistant bacteria are more susceptible to antibiotics and host-clearance mechanisms by the immune system”. These findings support phage application in therapy, although the overall statement that phage treatment selects the less virulent bacterial population should be further verified using a bigger collection of clinical strains.     

Is Biliary Lithogenesis Affected by Length and Implantation of Cystic Duct? (Study of 270 Patients with Endoscopic Retrograde Cholangiopancreatography)

The gallbladder seems to play an important rolein lithogenesis. Moreover, the morphology and theimplantation of the cystic duct may also influence thisprocess. Our purpose was to evaluate if the length and the implantation of the cystic duct mayaffect the formation of gallstones. Between April 1992and March 1994, 270 patients who underwent endoscopicretrograde cholangiopancreatography were included in the study, and the radiological length ofthe cystic duct was carefully recorded. Patients weredivided into two groups: I, absence of lithiasis: 113patients (65 men, 48 women); and II, gallbladder lithiasis or lithiasis in the common bile ductwith or without gallbladder lithiasis: 157 patients (73men, 84 women). A statistically significant differencewas observed among the two groups regarding the insertion of the cystic duct: implantationon the left side of the common bile duct represented arisk factor of lithiasis. The length of the cystic ductwas not directly implicated. Hypokinesis of the gallbladder is currently recognized asbeing a major factor in the initial steps oflithogenesis, but the implantation of the cystic ductcan play an important role by increasing cystic ductresistance and causing a reduced washout effect of thegallbladder contents, including cholesterolcrystals.     

Effects of Growth Hormone Deficiency and Recombinant Growth Hormone Therapy on Postprandial Gallbladder Motility and Cholecystokinin Release

In addition to cholecystokinin, other hormones have been suggested to be involved in regulation of postprandial gallbladder contraction. We aimed to evaluate effects of growth hormone (GH) on gallbladder contractility and cholecystokinin release. Gallbladder and gastric emptying (by ultrasound) and cholecystokinin release were determined before and after 6 months of recombinant human GH (rhGH) therapy in 12 patients with GH deficiency, after either a mixed (n = 5) or a liquid (n = 7) meal. Basal postprandial gallbladder contraction was severely impaired (19 +/- 2 and 26 +/- 3% of fasting volume after mixed and liquid meal, respectively). Histology and cholecystokinin sulfation patterns in duodenal biopsies from two patients were normal. After 6 months of rhGH therapy, fasting gallbladder volumes increased (from 20.8 +/- 0.9 to 25.9 +/- 1.1 mL, P < 0.05) and postprandial gallbladder emptying was restored (70 +/- 6 and 70 +/- 7% of fasting volume after mixed and liquid meal, respectively), without change of gastric emptying. Cholecystokinin secretion after a mixed meal and gallbladder sensitivity to cholecystokinin were significantly enhanced during rhGH replacement compared to the basal state. Postprandial cholecystokinin release, gallbladder responsiveness to cholecystokinin, and gallbladder emptying are severely impaired in the absence of GH. Reversibility during GH suppletion suggests its involvement in regulation of gallbladder contractility.     

IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test

Objective:

IDegLira is a novel, fixed-ratio combination of the long-acting basal insulin, insulin degludec, and the long-acting glucagon-like peptide-1 analog liraglutide. We studied the effect of IDegLira versus its components on postprandial glucose (PPG) in type 2 diabetes.

Methods:

In this substudy, 260 (15.6%) of the original 1663 patients with inadequate glycemic control participating in a 26-week, open-label trial (DUAL I) were randomized 2:1:1 to once-daily IDegLira, insulin degludec or liraglutide. Continuous glucose monitoring (CGM) for 72 hours and a meal test were performed.

Results:

At week 26, IDegLira produced a significantly greater decrease from baseline in mean PPG increment (normalized iAUC_0-4h) than insulin degludec (estimated treatment difference [ETD] −12.79 mg/dl [95% CI: −21.08; −4.68], P = .0023) and a similar magnitude of decrease as liraglutide (ETD −1.62 mg/dl [95% CI: −10.09; 6.67], P = .70). CGM indicated a greater reduction in change from baseline in PPG increment (iAUC_0-4h) for IDegLira versus insulin degludec over all 3 main meals (ETD −6.13 mg/dl [95% CI: −10.27, −1.98], P = .0047) and similar reductions versus liraglutide (ETD −1.80 mg/dl [95% CI: −2.52, 5.95], P = .4122). Insulin secretion ratio and static index were greater for IDegLira versus insulin degludec (P = .048 and P = .006, respectively) and similar to liraglutide (P = .45 and P = .895, respectively).

Conclusions:

Once-daily IDegLira provides significantly better PPG control following a mixed meal test than insulin degludec. The improvement is at least partially explained by higher endogenous insulin secretion and improved beta cell function with IDegLira. The benefits of liraglutide on PPG control are maintained across all main meals in the combination.     

Determinants of Occurrence and Volume of Transpyloric Flow During Gastric Emptying of Liquids in Dogs

The precise factors and their relative contributions that lead to individual flow pulses across the pylorus during liquid gastric emptying remain unclear. Our objective was to determine the factors leading to individual flow pulses, their relative contributions and the role of the vagus nerve in their modulation. Proximal gastric tone had a strong positive correlation with the volume of the corresponding transpyloric flow pulse whereas pyloric tone had an inverse correlation. Antral contractions were associated with the presence but not the volume of the pulse. Acute vagal blockade retarded emptying via loss of proximal gastric tone and increased outflow resistance and loss of propagating antral pressure waves. In conclusion, the major determinants of the volume of pulsatile transpyloric flow are proximal gastric and pyloric tone. The vagus nerve plays a key role in regulating both proximal gastric and pyloric tone as well as moderating propagating antral contractions.     

Limbic Encephalitis Brain Damage Induced by Cocal Virus in Adult Mice Is Reduced by Environmental Enrichment: Neuropathological and Behavioral Studies

We previously demonstrated, using the Piry virus model, that environmental enrichment promotes higher T-cell infiltration, fewer microglial changes, and faster central nervous system (CNS) virus clearance in adult mice. However, little is known about disease progression, behavioral changes, CNS cytokine concentration, and neuropathology in limbic encephalitis in experimental models. Using Cocal virus, we infected C57Bl6 adult mice and studied the neuroanatomical distribution of viral antigens in correlation with the microglial morphological response, measured the CNS cytokine concentration, and assessed behavioral changes. C57Bl6 adult mice were maintained in an impoverished environment (IE) or enriched environment (EE) for four months and then subjected to the open field test. Afterwards, an equal volume of normal or virus-infected brain homogenate was nasally instilled. The brains were processed to detect viral antigens and microglial morphological changes using selective immunolabeling. We demonstrated earlier significant weight loss and higher mortality in IE mice. Additionally, behavioral analysis revealed a significant influence of the environment on locomotor and exploratory activity that was associated with less neuroinvasion and a reduced microglial response. Thus, environmental enrichment was associated with a more effective immune response in a mouse model of limbic encephalitis, allowing faster viral clearance/decreased viral dissemination, reduced disease progression, and less CNS damage.