GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans.

GLP-1 receptor agonists (GLP-1RAs) are effective anti-obesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to obese patients and observed heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1R neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMHGLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMHGLP-1R neurons selectively during eating behavior. We further identified an intricate interplay between DMHGLP-1R neurons and arcuate NPY/AgRP neurons (ARCNPY/AgRP), to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering novel neural targets for obesity and metabolic diseases.

Lateral hypothalamic leptin receptor neurons drive hunger-gated food-seeking and consummatory behaviours in male mice.

For survival, it is crucial for eating behaviours to be sequenced through two distinct seeking and consummatory phases. Heterogeneous lateral hypothalamus (LH) neurons are known to regulate motivated behaviours, yet which subpopulation drives food seeking and consummatory behaviours have not been fully addressed. Here, in male mice, fibre photometry recordings demonstrated that LH leptin receptor (LepR) neurons are correlated explicitly in both voluntary seeking and consummatory behaviours. Further, micro-endoscope recording of the LHLepR neurons demonstrated that one subpopulation is time-locked to seeking behaviours and the other subpopulation time-locked to consummatory behaviours. Seeking or consummatory phase specific paradigm revealed that activation of LHLepR neurons promotes seeking or consummatory behaviours and inhibition of LHLepR neurons reduces consummatory behaviours. The activity of LHLepR neurons was increased via Neuropeptide Y (NPY) which acted as a tonic permissive gate signal. Our results identify neural populations that mediate seeking and consummatory behaviours and may lead to therapeutic targets for maladaptive food seeking and consummatory behaviours.

Surgical strategy for colonic intussusception caused by a giant colonic lipoma: a report of two cases and a review of the literature.

A colon lipoma is a remarkably rare tumor. In most cases, the tumors are asymptomatic and small in size, need to be differentiated from malignant tumors, and do not need any special treatment. Selection of the right surgical strategy depends on the status of bowel, as well as the size and the location of tumor. We encountered two patients with giant submucosal lipomas that had induced intussusceptions: one with a lipoma in the transverse colon and the other with a lipoma in the ascending colon. The diagnoses were made by using histological examinations. We report the clinical features, diagnoses, and treatments of, as well as our experience with, these two uncommon cases, and we present a review of the literature on this subject.

A stercoral perforation of the rectum.

A stercoral perforation of the rectum due to a fecaloma is a rare disease with a high mortality rate. Although multiple case reports of colonic perforations have been published, the data regarding rectal perforations are limited. This case report will highlight one such case of a stercoral rectal perforation that was successfully treated with a laparoscopic operation.

The efficiency of IV PCA with remifentanil and ketorolac after laparoscopic-assisted vaginal hysterectomy.

BACKGROUND: This randomized, double-blinded clinical study was designed to evaluate the efficiency and safety of remifentanil with ketorolac for IV PCA after laparoscopic-assisted vaginal hysterectomy. METHODS: Eighty patients were randomly allocated into four groups. Group R received IV PCA using only remifentanil at a basal rate of 0.025 µg/kg/min and a bolus of 0.375 µg/kg. Group RK1 received IV PCA using remifentanil at a basal rate of 0.015 µg/kg/min and a bolus of 0.225 µg/kg. Group RK2 received IV PCA using remifentanil at a basal rate of 0.0075 µg/kg/min and a bolus of 0.1125 µg/kg. Group F received IV PCA using fentanyl at a basal rate of 0.3 µg/kg/h and a bolus of 0.075 µg/kg. In addition, ketorolac at a basal rate of 0.04 mg/kg/h and a bolus of 0.01 mg/kg was added to Group RK1, RK2, and F. All PCA conditions had a lock out period of 15 minutes. Pulse rate, systolic and diastolic BP, sedation score, visual analogue scale (VAS), and PONV score were recorded at 1, 3, 6, 12, and 24 hours after the operation. Total opioid use and the patients' number for rescue analgesic drug were also collected. RESULTS: The groups did not differ in PONV score and hemodynamic changes. The VAS in Group RK2 was high compared with the other groups. In addition, the sedation score was high in Group R. CONCLUSIONS: The additional ketorolac administration in remifentanil IV PCA had remifentanil sparing effects and reduced sedation among the side effects. Further studies will be needed to evaluate the precise and adequate dosage of ketorolac.

Preparation and characterization of biodegradable nanoparticles entrapping immunodominant peptide conjugated with PEG for oral tolerance induction.

PEG-conjugated immunodominant peptides for collagen-induced arthritis (CIA) were prepared for oral tolerance induction instead of whole Type II collagen (CII), because a small peptide can be converted to a macromolecule soluble in methylene chloride by the coupling of poly-ethylene glycol (PEG). PEG-pep1 was synthesized from a peptide and mPEG-NH2 (Mw approximately 5000) using SPDP as a linker, whereas PEG-pep2 was prepared by the direct disulfide coupling between PEG-OD (Mw approximately 10,000) and the peptide. PEG-pep1 and PEG-pep2 were purified by gel permeation chromatography (GPC), and the peak fractions of GPC were identified by GPC and MALDI-TOF mass spectroscopy. The peptide coupling gave much earlier retention times for PEG-pep1 (11.26 min) and PEG-pep2 (10.61 min) than for mPEG-SPDP (15.63 min) and mPEG-OD (14.58 min). The Mw's of mPEG-NH2, mPEG-SPDP, PEG-pep1, mPEG-OD and PEG-pep2 were 5451, 5588, 7035, 10,360 and 11,826, respectively, suggesting that PEG-pep1 and PEG-pep2 of high purity could be obtained. The nanoparticles entrapping PEG-pep1 and PEG-pep2 (NP/PEG-pep1 and NP/PEG-pep2) were prepared by the o/w solvent evaporation method, whereas the peptide-loaded nanoparticles (NP/pep) were prepared by the w/o/w double emulsion method. Although all the nanoparticles had a similar spherical morphology under scanning electron microscopy, NP/pep showed up as having a larger mean size than the others, which was confirmed by dynamic light scattering analysis (NP/pep, 499.7+/-27.2 nm; NP/PEG-pep1, 333.0+/-16.8 nm; NP/PEG-pep2, 342.4+/-15.1 nm). The lower encapsulation efficiency of NP/pep (21.0+/-1.6%) than NP/PEG-pep1 (66.5+/-5.0%) and NP/PEG-pep2 (73.8+/-5.5%) can also be attributed to the preparation method. In in vitro release studies, NP/PEG-pep1 and NP/PEG-pep2 displayed a similar release profile, close to a linear release pattern, whereas NP/pep displayed a tri-phasic release profile. From these results, it was demonstrated that nanoparticles entrapping a PEG-conjugated peptide could be an alternative delivery method for the induction of oral tolerance rather than CII and peptide.