Neuroprotective effect of liraglutide and memantine in a rat model of Alzheimer’s disease

Objective:To assess the effect of memantine combined with liraglutide on aluminum chloride(AlCl_(3))and D-galactose(D-GAL)-induced neurotoxicity in rats.Methods:Male Wistar rats were divided into 5 groups of 5 animals each:the positive control,the negative control,the memantine-treated group,the liraglutide-treated group,and the combination group treated with memantine and liraglutide.AlCl_(3)and D-GAL were used to induce neurotoxicity.Behavioral tests,brain beta-amyloid protein,and oxidative stress biomarkers were evaluated.Results:The Morris water maze test indicated an enhanced memory in the combination group.Moreover,the combination treatment of liraglutide and memantine resulted in a remarkable reduction in the beta-amyloid protein level in the brain tissue.Neuronal inflammation and oxidative stress biomarkers were significantly reduced,and the levels of antioxidant parameters were enhanced.Conclusions:The combination of liraglutide and memantine exerts neuroprotective effects and enhances memory and cognitive functions in rats with Alzheimer’s disease.

Surgical strategies for challenging common bile duct stones in the endoscopic era: A comprehensive review of current evidence

While endoscopic retrograde cholangiopancreatography(ERCP)remains the primary treatment modality for common bile duct stones(CBDS)or choledocho-lithiasis due to advancements in instruments,surgical intervention,known as common bile duct exploration(CBDE),is still necessary in cases of difficult CBDS,failed endoscopic treatment,or altered anatomy.Recent evidence also supports CBDE in patients requesting single-step cholecystectomy and bile duct stone removal with comparable outcomes.This review elucidates relevant clinical anatomy,selection indications,and outcomes to enhance surgical understanding.The selection between trans-cystic(TC)vs trans-choledochal(TD)approaches is described,along with stone removal techniques and ductal closure.Detailed surgical techniques and strategies for both the TC and TD approaches,including instrument selection,is also provided.Additionally,this review comprehensively addresses operation-specific complications such as bile leakage,stricture,and entrapment,and focuses on preventive measures and treatment strategies.This review aims to optimize the management of CBDS through laparoscopic CBDE,with the goal of improving patient outcomes and minimizing risks.

Histological study of the structural layers around the esophagus in the lower mediastinum

BACKGROUND In Japan,the transhiatal approach,including lower mediastinal lymph node dissection,is widely performed for Siewert type II esophagogastric junction adenocarcinoma.This procedure is generally performed in a magnified view using laparoscopy or a robotic system,therefore,the microanatomy of the lower mediastinum is important.However,mediastinal microanatomy is still unclear and classification of lower mediastinal lymph nodes is not currently based on fascia or other microanatomical structures.AIM To clarify the fascia and layer structures of the lower mediastinum and classify the lower mediastinal tissue.METHODS We dissected the esophagus and surrounding organs en-bloc from seven cadavers fixed in 10%formalin.Organs and tissues were then cut at the level of the lower thoracic esophagus,embedded in paraffin,and serially sectioned.Tissue sections were stained with Hematoxylin-Eosin(all cadavers)and immunostained for the lymphatic endothelial marker D2-40(three cadavers).We observed the periesophageal fasciae and layers,and defined lymph node boundaries based on the fasciae.Lymphatic vessels around the esophagus were observed on immunostained tissue sections.RESULTS We identified two fasciae,A and B.We then classified lower mediastinal tissue into three areas,paraesophageal,paraaortic,and intermediate,using these fasciae as boundaries.Lymph nodes were found to be present and were counted in each area.The dorsal part of the intermediate area was thicker on the caudal side than on the cranial side in all cadavers.On the dorsal side,no blood vessels penetrated the fasciae in six of the seven cadavers,whereas the proper esophageal artery penetrated fascia B in one cadaver.D2-40 immunostaining showed lymphatic vessel connections between the paraesophageal and intermediate areas on the lateral and ventral sides of the esophagus,but no lymphatic connection between areas on the dorsal side of the esophagus.CONCLUSION Histological studies identified two fasciae surrounding the esophagus in the lower mediastinum and the layers separated by these fasciae were used to classify the lower mediastinal tissues.

Distribution of splenic artery lymph nodes and splenic hilar lymph nodes

BACKGROUND Total gastrectomy with splenectomy is the standard treatment for advanced proximal gastric cancer with greater-curvature invasion.As an alternative to splenectomy,laparoscopic spleen-preserving splenic hilar lymph node(LN)dissection(SPSHLD)has been developed.With SPSHLD,the posterior splenic hilar LNs are left behind.AIM To clarify the distribution of splenic hilar(No.10)and splenic artery(No.11p and 11d)LNs and to verify the possibility of omitting posterior LN dissection in laparoscopic SPSHLD from an anatomical standpoint.METHODS Hematoxylin&eosin-stained specimens were prepared from six cadavers,and the distribution of LN No.10,11p,and 11d was evaluated.In addition,heatmaps were constructed and three-dimensional reconstructions were created to visualize the LN distribution for qualitative evaluation.RESULTS There was little difference in the number of No.10 LNs between the anterior and posterior sides.For LN No.11p and 11d,the anterior LNs were more numerous than the posterior LNs in all cases.The number of posterior LNs increased toward the hilar side.Heatmaps and three-dimensional reconstructions showed that LN No.11p was more abundant in the superficial area,while LN No.11d and 10 were more abundant in the deep intervascular area.CONCLUSION The number of posterior LNs increased toward the hilum and was not neglectable.Thus,surgeons should consider that some posterior No.10 and No.11d LNs may remain after SPSHLD.

Biliary microlithiasis,sludge,crystals, microcrystallization,and usefulness of assessment of nucleation time

BACKGROUND:The process of microcrystallization,its sequel and the assessment of nucleation time is ignored.This systematic review aimed to highlight the importance of biliary microlithiasis,sludge,and crystals,and their association with gallstones,unexplained biliary pain,idiopathic pancreatitis, and sphincter of Oddi dysfunction.DATA SOURCES:Three reviewers performed a literature search of the PubMed database.Key words used were'biliary microlithiasis','biliary sludge','bile crystals','cholesterol crystallisation','bile microscopy','microcrystal formation of bile','cholesterol monohydrate crystals','nucleation time of cholesterol','gallstone formation','sphincter of Oddi dysfunction'and'idiopathic pancreatitis'.Additional articles were sourced from references within the studies from the PubMed search.RESULTS:We found that biliary microcrystals account for almost all patients with gallstone disease,7%to 79%with idiopathic pancreatitis,83%with unexplained biliary pain, and 25%to 60%with altered biliary and pancreatic sphincter function.Overall,the detection of biliary microcrystals in gallstone disease has a sensitivity ranging from 55%to 87%and a specificity of 100%.In idiopathic pancreatitis,the presence of microcrystals ranges from 47%to 90%.A nucleation time less than 10 days in hepatic bile or ultra-filtered gallbladder bile has a specificity of 100%for cholesterol gallstone disease.CONCLUSIONS:Biliary crystals are associated with gallstone disease,idiopathic pancreatitis,sphincter of Oddi dysfunction, unexplained biliary pain,and post-cholecystectomy biliary pain.Pathways of cholesterol super-saturation,crystallisation, and gallstone formation have been described with scientificsupport.Bile microscopy is a useful method to detect microcrystals and the assessment of nucleation time is a good method of predicting the risk of cholesterol crystallisation.

Microbiology of gallbladder bile in uncomplicated symptomatic cholelithiasis

BACKGROUND:Few studies have assessed microflora and their antibiotic sensitivity in normal bile and lithogenic bile with different types of gallstones. METHODS:We performed a case control study of 70 bile samples(35 cholesterol and 35 pigment stones from 51 females and 19 males,aged 21-72 years with a median age of 37 years)from patients who underwent laparoscopic cholecystectomy for uncomplicated cholelithiasis,and 20 controls(14 females and 6 males,aged 33-70 years with a median age of 38 years)who underwent laparotomy and had no gallbladder stone shown by ultrasound scan.The bile samples were aerobically cultured to assess microflora and their antibiotic susceptibility.The procedures were undertaken under sterile conditions. RESULTS:Thirty-eight(54%)of the 70 patients with gallstones had bacterial isolates.Nine isolates(26%)were from cholesterol stone-containing bile and 29 isolates (82%)from pigment stone-containing bile(P=0.01,t test). Twenty-eight of these 38(74%)bile samples were shown positive only after enrichment in brain heart infusion medium(BHI)(P=0.02,t test).The overall bacterial isolates from bile samples revealed E.coli predominantly,followed by P.aeruginosa,Enterococcus spp.,Klebsiella spp.and S. epidermidis.There were no bacterial isolates in the bile of controls after either direct inoculation or enrichment in BHI.CONCLUSIONS:Bacterial isolates were found in pigment stone-containing bile.Non-lithogenic bile revealed no bacteria,showing an association between gallstone formation and the presence of bacteria in bile.Antibiotic sensitivity patterns of isolated organisms were similar irrespective of the type of stone.

Porta-caval fibrous connections-the lesser-known structure of intrahepatic connective-tissue framework:A unified view of liver extracellular matrix

Knowledge about the connective-tissue framework of the liver is not systematized,the terminology is inconsistent and some perspectives on the construction of the hepatic matrix components are contradictory.In addition,until the last two decades of the 20th century,the connective-tissue sheaths of the portal tracts and the hepatic veins were considered to be independent from each other in the liver and that they do not make contact with each other.The results of the research carried out by Professor Shalva Toidze and his colleagues started in the 1970s in the Department of Operative Surgery and Topographic Anatomy at the Tbilisi State Medical Institute have changed this perception.In particular,Chanukvadze I showed that in some regions where they intersect with each other,the connective tissue sheaths of the large portal complexes and hepatic veins fuse.The areas of such fusion are called porta-caval fibrous connections(PCFCs).This opinion review aims to promote a systematic understanding of the hepatic connective-tissue skeleton and to demonstrate the hitherto underappreciated PCFC as a genuine structure with high biological and clinical significance.The components of the liver connective-tissue framework—the capsules,plates,sheaths,covers—are described,and their intercommunication is discussed.The analysis of the essence of the PCFC and a description of its various forms are provided.It is also mentioned that analogs of different forms of PCFC are found in different mammals.