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Nizatidine accelerates gastric emptying of a solid meal in rats.

Nizatidine, a new histamine-2-receptor antagonist, stimulates gastrointestinal motility in dogs and gastric emptying of liquids in rats. Effect of nizatidine on gastric emptying of a solid meal was investigated using a novel gastric emptying model in rats. Male Wistar rats (weighing 200-300 g) were supplied with powdered food containing 30 w/w% barium 14 hr before the beginning of the experiment and x-ray photography of rat stomach was taken under light ether anesthesia. Gastric emptying was assessed by percentage of a decrease in area 30 min after drug was injected intraperitoneally. There was a positive correlation between the area of the gastric outline and the weight of the gastric contents (r = 0.94, P < 0.01). Ether anesthesia itself did not affect gastric emptying. Nizatidine increased gastric emptying dose-dependently (emptied percentage; vehicle: 4.9 +/- 1.5%, 1 mg/kg: 7.2 +/- 0.4%, 3 mg/kg: 10.4 +/- 2.0%, 10 mg/kg: 16.7 +/- 4.9%, 30 mg/kg: 25.7 +/- 7.4%). N-Desmethyl nizatidine (NDM) also stimulated gastric emptying, but nizatidine S-oxide, cimetidine, an famotidine had no significant effects on gastric emptying. Nizatidine and neostigmine, but not NDM, at a subthreshold dose accelerated gastric emptying treated with a low dose of acetylcholine (0.1 mg/kg). Atropine (2 mg/kg, -30 min) did not modulate the gastroprokinetic action of nizatidine, but blocked that of NDM. These findings suggest that this noninvasive method may allow measurement of gastric emptying of solids accurately and that nizatidine and NDM facilitate gastric emptying probably mediated by a direct and/or an indirect (acetylcholinesterase inhibition) cholinergic mechanism.

Acetylcholine↗

Inhibitory effects of cholecystokinin on postprandial gastric myoelectrical activity.

While a number of studies have investigated the effects of cholecystokinin (CCK) on gastrointestinal motility, little is known on the effects of CCK on gastric myoelectrical activity, which regulates gastric motility. The aim of this study was to investigate the effects of intravenous infusion of CCK-8 on gastric myoelectrical activity in normal humans. Gastric myoelectrical activity was measured in 10 healthy subjects with a noninvasive electrogastrographic technique by placing abdominal electrodes on the epigastric area. Two study sessions were performed in each subject on two separate days with double-blinded infusion of either saline or CCK (24 pmol/kg/hr). The procedure for each session was as follows: (A) 30-min baseline fasting electrogastrogram (EGG); (B) start infusion, another 30-min EGG; (C) give meal, 60-min EGG; and (D) stop infusion, another 60-min EGG. The dominant frequency and peak power (amplitude) of the EGG, and the percentage of normal 2-4 cycles/min slow waves during each recording session were computed and compared between placebo and CCK. It was found that normal 3 cpm slow waves were recorded in all EGGs. Infusion of CCK had no effect on the frequency of the gastric slow wave and did not induce gastric dysrhythmias. It was also found that intravenous infusion of CCK significantly decreased the EGG peak power (amplitude) during the first hour after the meal (the infusion was given during this period) in comparison with placebo (P < 0.05). This inhibitory effect on EGG peak power was sustained but not significant during the second postprandial hour (the infusion was not given during this period). It was concluded that intravenous infusion of CCK at a physiological concentration significantly decreased the postprandial EGG amplitude in normal humans, suggesting an inhibitory effect on postprandial gastric motility, but did not change the frequency and regularity of the gastric slow wave.

Adult↗

Autonomic dysfunction and the gastrointestinal tract.

Autonomic neuropathy of the gastrointestinal tract may represent a primary disorder, but much more often it is secondary due to systemic disorders like diabetes mellitus. This review gives an overview about the common clinical manifestations and the principles and limitations in diagnostic work-up of autonomic dysfunction of the gastrointestinal tract. Diagnostic evaluation usually includes a combination of screening tests for autonomic neuropathy and specialized diagnostic procedures for the detection of sequela of autonomic neuropathy in gastrointestinal motility.

Autonomic Nervous System Diseases↗

Effects of cisapride on the pancreatic exocrine secretion in rats.

Exocrine pancreatic secretion to intravenous injections of a new stimulant of gastrointestinal motility, R51,619 (cisapride) was studied in conscious rats, and in the isolated pancreatic acini in vitro. The injection of cisapride (2 mg/kg) significantly increased fluid, bicarbonate and protein output in vivo. Atropine completely abolished the pancreatic responses to cisapride, and CR 1409, a new glutaramic acid derivative and a competitive cholecystokinin (CCK) inhibitor, tended to decrease the cisapride-induced pancreatic exocrine secretion. However, amylase release and Ca2+ efflux from the isolated pancreatic acini were not stimulated. These results suggest that cisapride indirectly affects the pancreatic exocrine secretion primarily by releasing acethycholine from the intrapancreatic nerve endings and in part by releasing CCK from the duodenum, but has no direct action on the pancreas.

Acetylcholine↗

Assessing thrombosis risk in patients with idiopathic, diabetic, and postsurgical gastroparesis.

Patients with severe gastrointestinal motility disorders are often found to have intravenous access clots or deep venous thrombosis. It has previously been reported that many patients who have intravenous access thrombosis have concomitant thrombotic risk factors. In this study, the goal was to determine the underlying prevalence of hypercoagulable risk in a series of patients with documented gastroparesis. Investigators studied 62 consecutive patients (52 female; mean age, 42 y) who had symptoms of gastroparesis. All patients were evaluated for placement of a gastric neural stimulation device, or they had had one placed previously. Patients underwent a hematologic interview and standardized coagulation measures of thrombotic risk. Laboratory studies measured acquired elevations of Factor VII, Factor VIII, fibrinogen, lupus anticoagulant panel, antiphospholipid antibody panel, homocysteine (in the setting of kidney disease), and activated protein resistance. Investigators also measured congenital factors: Factor VIII (with C-reactive protein levels), antithrombin III, protein C, protein S (total and free), Factor II mutation, Factor V Leiden, methylenetetrahydrofolate reductase, and homocysteine. Fifty-five patients (89%) were found to have detectable hypercoagulable risk factors. Twenty-five of the 62 patients (40%) had a documented history of abnormal clotting, including deep venous thrombosis, intravenous access thrombosis, and pulmonary embolism. All patients with a previous history of thrombosis had detectable clotting abnormalities. Of 56 patients, 40 (71%) had hypercoagulability and did not have diabetes (P=.036), and 20 (36%) had hypercoagulability and no known history of infection. However, this value was not statistically significant when infection and hypercoagulability were compared (P=.408). A high prevalence of acquired and congenital hypercoagulable defects has been observed in patients with gastroparesis, which may predispose them to arterial and venous clots. This unique finding warrants consideration of coagulation evaluation in patients with severe gastroparesis, especially when these patients are placed in high-risk thrombophilic situations, such as hospitalization, prolonged intravenous access, and surgery.

Adult↗

Effects of salbutamol on the absorption and disposition of sulphamethoxazole in adult volunteers.

On the basis of the reports that beta-adrenergic stimulation affects gastrointestinal motility in man as well as induces N-acetyltransferase in rat pineal gland, we decided to assess the effects of salbutamol pretreatment on the absorption as well as disposition of sulphamethoxazole (SMZ). After a control pharmacokinetic study of SMZ, each of six healthy volunteers took salbutamol at a dose of 4 mg four times daily for two weeks, and the kinetic study of SMZ was repeated after the morning dose on the fifteenth day. None of SMZ half-life, volume of distribution, renal and hepatic clearance rates was significantly altered. However, salbutamol pretreatment resulted in significant reduction in the absorption rate constant of SMZ from 1.168 +/- 0.509 h-1 (mean +/- S.D.) to 0.688 +/- 0.348 h-1 (P less than 0.025), and this was associated with prolongation of tmax from 3.00 +/- 1.69 h to 4.33 +/- 1.51 h (P less than 0.025). Cmax, however, was not correspondingly reduced probably as a result of significant increase in the extent of SMZ absorption from 611 +/- 108 mg to 749 +/- 78 mg (P less than 0.025). Our findings suggest that beta-adrenergic stimulation does not significantly induce human hepatic N-acetyltransferase enzyme. However, it does reduce the absorption rate as well as increase the extent of absorption of SMZ.

Adult↗

Circulating somatostatin after oral glucose in hypothyroidism.

The response of circulating somatostatin-like immunoactivity (SLI) to oral glucose and its relation to other pancreatic islet cell hormones were studied in 10 hypothyroid subjects before and after treatment. None of the patients suffered from diabetes mellitus or obesity. Compared with normal controls, the hypothyroid subjects had higher fasting and stimulated SLI levels but lower fasting pancreatic glucagon levels. Integrated glucose and insulin responses following glucose ingestion were normal, but the peak insulin response was delayed to 120 min suggesting impaired pancreatic beta-cell response to oral glucose. On the other hand, the peak response of plasma C-peptide was higher probably because of a reduction in metabolic clearance. In both hypothyroid subjects and controls, a significant correlation was found between the maximal increment of SLI and the maximal decrement of glucagon following oral glucose. In conclusion, plasma SLI is increased in hypothyroidism. The changes in SLI may be due to either an increased hormonal secretion or a reduced metabolic clearance in hypothyroidism. This elevated SLI might contribute to the slower gastrointestinal motility observed in hypothyroidism. Our data also suggest that the reduction in glucagon secretion may be secondary to the increase in circulating SLI.

Adult↗

[Epidural analgesia in postoperative pain therapy. A review].

This review highlights the advantages of regional anaesthesia techniques, especially of epidural analgesia, for the management of postoperative and posttraumatic pain: excellent pain relief and a high degree of patient satisfaction, even compared to the gold standard of acute pain therapy, i.v. PCA with opioids. Further advantages of epidural analgesia (EA) are discussed, such as early recovery of gastrointestinal function, reduction of postoperative respiratory complications, lower incidence of myocardial ischema, better mobilisation, reduced risk of thromboembolism, lower incidence of chronic pain problems (such as phantom limb pain) etc. Nevertheless, many studies failed to show significant effects on outcome (e.g. mortality). Weighing the risks, costs and benefits of EA, this technique is indicated in case of significant postoperative pain, especially in case of painful mobilisation, in patients with significant pulmonary risk factors (ASA 3 or IV), in patients where an improved perfusion or gastrointestinal motility is deemed essential, and if chronic pain syndromes are common problems that should be prevented (e.g., amputation). For the praxis of epidural analgesia it is emphasised to place the catheter in an appropriate segment to obtain sufficient analgesia without side effects. Organisational structures (such as an acute pain service) and appropriate monitoring allow to continue EA with local anaesthetics and/or opioids on surgical wards. Recommendations are given for the monitoring of EA on surgical wards. Clear cut agreements should define the role of anaesthesiologists, surgeons and nurses in the management of patients treated with postoperative EA on surgical wards.

Analgesia, Epidural↗

[Combined anesthesia with epidural catheter. A retrospective analysis of the perioperative course in patients ungoing radical prostatectomy] .

Patients requiring radical prostatectomy (rPE), including retroperitoneal lymphadenectomy are often aged and have coexisting cardiopulmonary diseases, increasing the risk of perioperative complications. The aim of the present study was to evaluate our perioperative anaesthesiologic regimen over the last five years, in terms of safety and patients comfort. Records of 433 patients who underwent rPE between 1994 and 1999 in our hospital were retrospectively reviewed. Patients were divided in those who received: 1. general anaesthesia (GA) alone, 2. a combination of lumbar epidural anaesthesia (LEA) + GA or, 3. thoracic epidural anaesthesia (TEA) + GA. General anaesthesia was performed as balanced anaesthesia, and epidural administered local anaesthetics were bupivacaine 0.25% or ropivacaine 0.2%, 8-12 ml/h. In terms of intra- and postoperative numbers of tachycardiac and hypertensive episodes, a reduced stress response was observed under epidural anaesthesia (EA). Moreover, the weaning duration was shorter under EA and onset of gastrointestinal motility was found earlier ([h] GA: 50.6 +/- 11.1/LEA: 39.3 +/- 13.6/TEA: 33.8 +/- 13.0). Furthermore, a trend to rarer phases of postoperative vomiting and a significant decrease of in hospital stay of about one day ([d] GA: 12.4 +/- 5.8/LEA: 11.1 +/- 3.1/TEA: 11.5 +/- 3.8) was observed. The duration of personnel binding in the OR did not differ significantly between GA and TEA ([min] GA: 222.9 +/- 43.5/LEA: 238.2 +/- 41.8/TEA: 227.0 +/- 46.2), but ICU stay was shortened under TEA. Besides this, TEA reduced the number of pathologic postoperative thorax-x-rays. Senso-motor blockades, decreases of SaO2 and cardiac complications were experienced more frequent under LEA as compared with TEA. Combination of GA and EA, especially TEA, appears to improve perioperative care of patients undergoing rPE, in terms of patients safety and comfort.

Anesthesia, Epidural↗

[Aorto-mesenteric artery compression syndrome].

INTRODUCTION: The aim of this paper was to describe a rare gastrointestinal motility disorder caused by vascular compression of the duodenum. PATIENTS: The authors present two patients with vomiting and severe weight loss. Diagnostic evaluation revealed superior mesenteric artery syndrome. METHODS: After frustrane treatment with i.v. infusions, surgical intervention with laterolateral duodenojejunostomy or Roux-en-y reconstruction for restoration of the intestinal passage was performed. RESULTS: Following initial recovery, the first patient showed permanent anorexia. Psychosocial evaluation revealed a severe pathological mother-child relationship. Intensive psychological treatment finally achieved definite weight gain and complete recovery in this patient. The second case subsequently gained weight without psychological evaluation. CONCLUSION: The authors review the literature, pointing out the anatomy of the duodenojejunal angle, the etiology, and the predisposing factors, as well as diagnostic and therapeutic strategies.

Adolescent↗

The alpha-glucosidase inhibitor voglibose (AO-128) does not change pharmacodynamics or pharmacokinetics of warfarin.

OBJECTIVE: Voglibose is a new and potent inhibitor of alpha-glucosidases and is used for the treatment of diabetes mellitus. Since voglibose increases gastrointestinal motility and could thus affect absorption of concomitantly administered drugs, it was investigated whether or not voglibose modifies the pharmacodynamics and pharmacokinetics of warfarin, an oral anticoagulant frequently used in cardiovascular disorders likely to arise in diabetic patients. METHODS: Twelve healthy male subjects were given individually adjusted doses of warfarin to reduce prothrombin time (Quick's method) to a value of about 30-40% of the normal range within the first 8 days. Then, the individuals maintenance dose, given in the morning, was maintained until day 15. On study days 11-15, voglibose was co-administered per os in a dose of 5 mg t.i.d. The prothrombin time was determined on days 10 and 11 (reference) and on days 15 and 16 (test), and the steady-state pharmacokinetic characteristics of the warfarin enantiomers were determined on days 10 (reference) and 15 (test). The ratios test/reference were evaluated according to bioequivalence criteria. RESULTS: The equivalence ratio (test reference) for the pharmacodynamic parameter prothrombin time was 0.97 and for the pharmacokinetic characteristics AUC0-24 h.t.ss: S-(-)-warfarin, 1.05; R-(+)-warfarin, 1.01; and Cmax.ss: S-(-)-warfarin, 1.08; R-(+)-warfarin, 1.04. All parameters were within the predetermined accepted range of 0.7-1.43 (pharmacodynamics) or 0.8-1.25 (pharmacokinetics), thus fulfilling equivalence criteria. CONCLUSIONS: Voglibose modified neither the pharmacodynamics nor the pharmacokinetics of warfarin under steady-state conditions. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.

Adult↗

Researching on new species of "Mate": Ilex brevicuspis: phytochemical and pharmacology study.

BACKGROUND: Ilex paraguariensis St. Hilaire (Aquifoliaceae) ("Mate" or "Yerba mate") is one of the most commercialized plants of South America which grows naturally in NE Argentina, Uruguay, SE Brazil and E Paraguay, where it is also cultivated. It is used to prepare a tea-like beverage (infusions or decoctions) appreciated for its peculiar flavor, stimulation and nutritional properties. Ilex brevicuspis Reisseck grows in the same habitat and is widely used as a substitute or adulterant of Ilex paraguariensis. In a previous work, methylxanthines (caffeine, theobromine and theophylline) were not detected in it by HPLC. AIM OF THE STUDY: This study was undertaken in order to isolate, identify and quantify the polyphenolic compounds (caffeoyl derivatives and flavonoids) and to investigate some of the pharmacological activities of I. brevicuspis, related with the traditional use of the "Mate" (choleretic, intestinal propulsion and antioxidant activities). Acute toxicity was also investigated. METHODS: Decoctions, like extracts, were prepared in order to compare the results with preparations commonly used by the local people. For the phytochemical analysis, the extracts were analyzed by HPLC with a diode array detector. Choleretic and intestinal propulsion activities were assayed in rats. Sodium dehydrocholate (DHC) was used as a choleretic reference standard. Antioxidant activity was tested in liposomes that were oxidized by the free radical generator 2,2'-azobis [amidinopropane] chloride (AAPH). RESULTS: For the first time in I. brevicuspis the following compounds were isolated and quantified: A) caffeoyl derivative compounds (chlorogenic acid; caffeic acid; 3,4-dicaffeoylquinic acid; 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid. B) flavonoids (rutin, quercetin and kaempferol). Biological activity assays demonstrated that I. brevicuspis extracts produced a significant increase of bile flow (BF) in rats in the first 30 min period and in the percentage of BF increase accumulated at 120 min. It also produced an increase in the intestinal propulsion activity. Moreover, this species showed a high antioxidant activity. The acute toxicity test showed that Ilex brevicuspis did not produce any sign of toxicity at the analyzed doses. CONCLUSIONS: An Argentinean Ilex specie ( I. brevicuspis) has choleretic, intestinal propulsion, antioxidant activities and these results may lead to the potential development of a new "Yerba Mate" and/or phytopharmaceutical products, without central nervous system (CNS) stimulant activity.

Animals↗

Distribution of heme oxygenase 2 in nerves and c-kit(+) interstitial cells in human stomach.

Different populations of interstitial cells (ICs) may serve as gut pacemakers or as intermediaries between enteric nerves and smooth muscle cells. However, very little is known about the substances that ICs might use to communicate with other cells and no data are available in humans. Because carbon monoxide (CO) is emerging as a putative mediator in the regulation of gastrointestinal motility, this study examined the presence of heme oxygenase (HO2), the constitutive form of the enzyme for CO production, in human stomach with particular attention to ICs. The distribution of HO2 in nerves and ICs in human antrum was studied using specific antibodies. The immunostaining was observed using confocal laser scanning microscopy. HO2 immunoreactivity was found in myenteric neurons and nerve fibers supplying the circular muscle layer and in intramuscular c-kit(+) ICs, but not in c-kit(+) ICs surrounding the myenteric ganglia. The presence of HO2 in different cell types suggests that CO may serve as an intercellular messenger between myenteric neurons and ICs and between ICs and smooth muscle cells in human stomach.

Adult↗

Involvement of cholecystokinin receptor in the inhibition of gastric emptying by oxytocin in male rats.

The effects of oxytocin (OT) on gastric emptying and plasma levels of cholecystokinin (CCK) were studied in male rats. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na2(51)CrO4. Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Blood samples were collected for OT and CCK radioimmunoassay. After administration of OT (0.2-0.8 mg x kg(-1)), gastric emptying was inhibited, whereas plasma concentrations of OT and CCK were increased in a dose-dependent manner. Atosiban, an oxytocin receptor antagonist, effectively attenuated the OT-induced inhibition of gastric emptying. However, administration of atosiban alone had no effect on gastric emptying. Devazepide (3 mg x kg(-1)), a selective CCKA receptor antagonist, effectively attenuated the OT-induced inhibition of gastric emptying. L-365, 260, a selective CCKB receptor antagonist, did not alter the OT-induced inhibition of gastric emptying. These results suggest that OT inhibits gastric emptying in male rats via a mechanism involving CCK stimulation and CCKA receptor activation.

Animals↗

Nitric oxide synthase in the gastrointestinal tract of the estuarine crocodile, Crocodylus porosus.

The aim of this study was to investigate the distribution of nitric oxide synthase (NOS)-containing nerve cells in the gastrointestinal tract of a reptile and to compare it with the pattern in other vertebrate classes. In the estuarine crocodile, Crocodylus porosus, NOS-positive nerve cell bodies and fibres were found in all regions of the gut examined. Most myenteric microganglia contained one or several NOS-immunoreactive neurons together with unlabelled neurons. The majority of the neurons were multipolar, ranging from 10 to 25 microns in diameter. Both the circular and the longitudinal muscle layers were innervated by NOS-immunoreactive nerve fibres, which mostly ran parallel to the muscle fibres. In addition, small blood vessels in the submucosa and on the serosal surface of the gut were innervated by NOS-immunoreactive fibres. Double labelling with antisera to NOS and vasoactive intestinal peptide (VIP) revealed three neuronal subpopulations. A small proportion of the NOS-immunoreactive cells also contained immunoreactivity to VIP while a majority of the VIP-immunoreactive cells were NOS immunoreactive. There were more nerve fibres showing VIP immunoreactivity than fibres with NOS immunoreactivity, although most of the latter also contained immunoreactivity to VIP. VIP-immunoreactive fibres often surrounded the NOS-immunoreactive nerve cells. These results suggest that neuronally released nitric oxide is likely to be involved in the control of gastrointestinal motility in the crocodile as in most other vertebrate species.

Alligators and Crocodiles↗

Gastrointestinal function and quality of life after pylorus-preserving pancreatoduodenectomy.

The pylorus-preserving pancreatoduodenectomy (PPPD) has taken the place of the conventional Whipple pancreatoduodenectomy as the standard procedure for various periampullary disease. With recent advances in surgical techniques and improvements in perioperative management, the number of long-term survivors after PPPD is increasing. As a result, surgeons should pay more attention to the patients' postoperative gastrointestinal function, nutrition, and quality of life (QOL). Gastric stasis, which is a frequent complication during the early postoperative period after PPPD, prolongs the hospital stay and impairs the QOL in the intermediate term. Several possible pathogeneses for this gastric stasis have been postulated; however, the precise mechanism remains unclear. The gastric emptying function gradually recovers to the preoperative level by 6 months after PPPD. Pancreatic functions are likely to be maintained for at least 1 year after PPPD; however, in some cases, they tend to gradually deteriorate over time after the operation, depending on the type of pancreatic reconstruction or the preoperative condition of the pancreas. It is important to note that preoperative and postoperative pancreatic exocrine function strongly influence the postoperative outcome regarding such factors as pancreatic fistula, body weight maintenance, nutrition, and the QOL. The QOL, as assessed by questionnaire, normally returns to the preoperative level within 6 months after PPPD, and this correlates with the changes in gastrointestinal function and nutritional status. It still remains an unresolved question, however, whether the Billroth-I PPPD really leads to better long-term nutritional status, but worse early gastric emptying function, than the Billroth-II type of reconstruction.

Gastric Emptying↗

Central regulation of hepatic function by neuropeptides.

In addition to classical neurotransmitters, such as acetylcholine and noradrenaline, neuropeptides have been recognized as new neurotransmitters and neuromodulators. Neuropeptides are widely distributed in the central nervous system as well as in peripheral nerves, and act as neurotransmitters to regulate various physiological functions. The digestive organs are no exception, and several neuropeptides in the central nervous system are shown to act in specific brain sites and control gastrointestinal functions, such as gastric acid secretion, and gastrointestinal motility, through the autonomic nervous system. Recently, a relationship between central neuropeptides and hepatic function through the autonomic nervous system has been revealed in animal models. Thyrotropin-releasing hormone acts in the medulla, in particular in the left dorsal vagal complex, to induce stimulation of hepatic blood flow and hepatic proliferation, and protect against experimental liver injury through vagal and cholinergic pathways. Corticotropin-releasing factor injected intracisternally elicits inhibition of the hepatic blood flow and exacerbates experimental liver injury through sympathetic and noradrenergic pathways. Neuropeptide Y acts in the left dorsal vagal complex, in particular in regard to the Y1 receptor subtype, to stimulate bile secretion. Other neuropeptides such as beta-endorphin and bombesin in the brain modulate hepatic proliferation and bile secretion. Through the use of neuropeptides, new knowledge of the central and peripheral mechanisms underlying brain regulation of hepatic function will be revealed. Further studies in regard to the physiological relevance of the central action of neuropeptides on specific brain sites should be performed to unravel the underlying pathways that mediate brain-liver interaction.

Central Nervous System↗