Hepatic Portal Area Research Articles

Diagnostic value of identifying location and amount of free gas in the abdominal cavity by multidetector computed tomography in patients with acute gastrointestinal perforation

Objective: To evaluate the relationships between the location and extent of diffusion of free intraperitoneal air by multi-slice spiral CT (MSCT) and between the location and size of acute gastrointestinal perforation. Methods: This was a descriptive case series. We examined abdominal CT images of 33 patients who were treated for intraoperatively confirmed gastrointestinal perforation (excluding appendiceal perforation) in the Department of General Surgery, Nanfang Hospital between January and September 2022. We identified five locations of intraperitoneal air: the subphrenic space, hepatic portal space, mid-abdominal wall, mesenteric space, and pelvic cavity. We allocated the 33 patients to an upper gastrointestinal perforation (n=23) and lower gastrointestinal perforation group (n=10) base on intraoperative findings and analyzed the relationships between the locations of free gas and of gastrointestinal perforation. Additionally, we established two models for analyzing the extent of diffusion of free gas in the abdominal cavity and constructed receiver operating characteristic (ROC) curves to analyze the relationships between the two models and the size of the gastrointestinal perforation. Results: In the upper gastrointestinal perforation group, free gas was located around the hepatic portal area in 91.3% (21/23) of patients: this is a significantly greater proportion than that found in the lower gastrointestinal perforation group (5/10) (P=0.016). In contrast, free gas was located in the mesenteric interspace in 8/10 patients in the lower gastrointestinal perforation group; this is a significantly greater proportion than was found in the upper gastrointestinal perforation group (8.7%, 2/23) (P<0.010). The sensitivity of diagnosis of upper gastrointestinal perforation base on the presence of hepatic portal free gas was 84.8% and the specificity 71.4%. Further, the sensitivity of diagnosis of lower gastrointestinal perforation base on the presence of mesenteric interspace free gas was 80.0% and the specificity 91.3%. The rates of presence of free gas in the subdiaphragmatic area, mid-abdominal wall, and pelvic cavity did not differ significantly between the two groups (all P>0.05). Receiver operating characteristic curves showed that when free gas was present in four or more of the studied locations in the abdominal cavity, the optimal cutoff for perforation diameter was 2 cm, the corresponding sensitivity 66.7%, and the specificity 100%, suggesting that abdominal free gas diffuses extensively when the diameter of the perforation is >2 cm. Another model revealed that when free gas is present in three or more of the studied locations, the optimal cutoff for perforation diameter is 1 cm, corresponding to a sensitivity of 91.7% and specificity of 76.2%; suggesting that free gas is relatively confined in the abdominal cavity when the diameter of the perforation is <1 cm. Conclusion: Identifying which of five locations in the abdominal cavity contains free intraperitoneal air by examining MSCT images can be used to assist in the diagnosis of the location and size of acute gastrointestinal perforations.

Dietary 1,3-β-Glucans Affect Growth, Breast Muscle Composition, Antioxidant Activity, Inflammatory Response, and Economic Efficiency in Broiler Chickens.

Recently, researchers have been intensively looking for novel, safe antibiotic alternatives because of the prevalence of many clinical and subclinical diseases affecting bird flocks and the risks of using antibiotics in subtherapeutic doses as feed additives. The present study intended to evaluate the potential use of 1,3-β-glucans (GLC) as antibiotic alternative growth promotors and assessed the effect of their dietary inclusion on the growth performance, carcass traits, chemical composition of breast muscles, economic efficiency, blood biochemical parameters, liver histopathology, antioxidant activity, and the proinflammatory response of broiler chickens. This study used 200 three-day-old ROSS broiler chickens (50 chicks/group, 10 chicks/replicate, with an average body weight of 98.71 ± 0.17 g/chick). They were assigned to four experimental groups with four dietary levels of GLC, namely 0, 50, 100, and 150 mg kg-1, for a 35-day feeding period. Birds fed diets containing GLC showed an identical different growth rate to the control group. However, the total feed intake (TFI) increased quadratically in the GLC50 and GLC100 groups as compared to that in the control group. GLC addition had no significant effect on the weights of internal and immune organs, except for a decrease in bursal weight in the GLC150 group (p = 0.01). Dietary GLC addition increased the feed cost and total cost at 50 and 100 mg kg-1 doses. The percentages of n-3 and n-6 PUFA in the breast muscle of broiler chickens fed GLC-supplemented diets increased linearly in a dose-dependent manner (p < 0.01). The serum alanine aminotransferase (ALT) level and the uric acid level were quadratically increased in the GLC150 group. The serum levels of total antioxidant capacity, catalase, superoxide dismutase, interleukin-1β, and interferon-gamma linearly increased, while the MDA level decreased in the GLC-fed groups in a dose-dependent manner. Normal histological characterization of different liver structures in the different groups with moderate round cells was noted as a natural immune response around the hepatic portal area. The different experimental groups showed an average percentage of positive immunostaining to the proinflammatory marker transforming growth factor-beta with an increase in the dose of GLC addition. The results suggest that GLC up to 100 mg kg-1 concentration can be used as a feed additive in the diets of broiler chickens and shows no adverse effects on their growth, dressing percentage, and internal organs. GLC addition in diets improves the antioxidant activity and immune response in birds. GLC help enrich the breast muscle with n-3 and n-6 polyunsaturated fatty acids.

Sensory representation and detection mechanisms of gut osmolality change.

Ingested food and water stimulate sensory systems in the oropharyngeal and gastrointestinal areas before absorption1,2. These sensory signals modulate brain appetite circuits in a feed-forward manner3-5. Emerging evidence suggests that osmolality sensing in the gut rapidly inhibits thirst neurons upon water intake. Nevertheless, it remains unclear how peripheral sensory neurons detect visceral osmolality changes, and how they modulate thirst. Here we use optical and electrical recording combined with genetic approaches to visualize osmolality responses from sensory ganglion neurons. Gut hypotonic stimuli activate a dedicated vagal population distinct from mechanical-, hypertonic- or nutrient-sensitive neurons. We demonstrate that hypotonic responses are mediated by vagal afferents innervating the hepatic portal area (HPA), through which most water and nutrients are absorbed. Eliminating sensory inputs from this area selectively abolished hypotonic but not mechanical responses in vagal neurons. Recording from forebrain thirst neurons and behavioural analyses show that HPA-derived osmolality signals are required for feed-forward thirst satiation and drinking termination. Notably, HPA-innervating vagal afferents do not sense osmolality itself. Instead, these responses are mediated partly by vasoactive intestinal peptide secreted after water ingestion. Together, our results reveal visceral hypoosmolality as an important vagal sensory modality, and that intestinal osmolality change is translated into hormonal signals to regulate thirst circuit activity through the HPA pathway.

To Evaluate the Inhibition Leukemia Cell Effect of Haploidentical Spleen in Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation

[Objective] To evaluate the inhibition leukemia cell effect of haploidentical spleen in nonmyeloablative allogeneic hematopoietic stem cell transplantation.[Method] Take C57/BL/6 inbred mice (B6 mice) of 8-12 weeks as donor rats. Extract their bone marrow and spleen cells. P815 cells were as mast cell tumor cells (leukemia cells) of DBA/2 mice. The first generation 6D2F1 rats (F1 rats) were as recipients who were hybridized by C57/BL/6 mice and DBA/2 mice. F1 rats were made with the nonmyeloablative conditioning regimen CTX 300mg/m2 /d intraperitoneal injection on the hematopoietic stem cell transplantation -5d, -4d, -3d. In day 0, Group A-D were infused spleen + bone marrow cells +P815 cells; bone marrow cells + P815 cells; P815 cells and RPMI1640 culture medium respectively to compare the status of the mice blood, aGVHD and the pathological tumor infiltration of skin, liver and colon.[Results] 1. aGVHD score: the aGVHD score of group A was 2-4 who were alive on the 14th day after transplantation. The death occured on the fifteenth day. The clinical score was 6 on the twenty-sixth day for the 2 alive mice, and the rest of the mice were scored at 0-3. In group B, the mice began to die on the sixth day, and only 1 survived at the end of the thirtieth day. Group C died all in eighteenth days. 2. Pathological observation: the liver inflammatory cell infiltration in Group A, portal area of liver cell atrophy and necrosis of hepatic portal area and central veins focal infiltration of tumor cells or a small amount of infiltration could be observed. In Group B, the number of hepatocytes in the liver of the mice was decreased, and the infiltration of the tumor in the liver sinus was diffuse.[Conclusion] In nonmyeloablative allogeneic hematopoietic stem cell transplantation, the MHC haploidentical spleen may inhibit leukemia cell effect.[Discussion] Group A, compared with Group B and C, showed the aGVHD effect, as well as GVL effect. The spleen of haploidentical nonmyeloablative hematopoietic stem cell transplantation may make chimerism of immune cells of B6 mice and hematopoietic immune cells of F1 mice. The activated lymphocyte of the spleen of B6 mice and F1 mice could identify, monitor, inhibit and kill P815 cells. In nonmyeloablative allogeneic hematopoietic stem cell transplantation, the MHC haploidentical spleen may inhibit leukemia cell effect. DisclosuresNo relevant conflicts of interest to declare.

Glisson pedicle ligation for unresectable hepatocellular carcinoma

Abstract Introduction: Hepatocellular carcinoma (HCC) is 1 of the most common malignant neoplasms worldwide. Surgical resection is the first choice of treatment. However, surgical resection is unsuitable for certain types of HCC. Patient concerns: A 47-years-old male patient presented with Child-Pugh class A liver function and the indocyanine green retention rate at 15 min effectively was 3.5%. Computed tomography and magnetic resonance imaging indicated that the tumors were distributed in the anterior segment of right lobe, and near the hepatic portal area. The maximum size of the tumor was approximately 86mm×82 mm. Diagnosis: The patient was diagnosed with hepatocellular carcinoma Stage IIIB. After pre-operative evaluation, hepatic segmentectomy by Glisson pedicle approach was recommended. Interventions: Hepatic segmentectomy by Glisson pedicle approach was recommended. But there was heavy bleeding during hepatic resection after the ligation of the Glisson pedicle on the right anterior branches. Hence only Glisson pedicle ligation was performed without hepatic segmentectomy. Outcomes: During 1 year of postoperative follow-up, the patient had no obvious complications. The computed tomography and magnetic resonance imaging indicated significant reduction in the size of tumor. The tumor was observed to have undergone liquefaction necrosis after 6 months. The serum a-fetoprotein also decreased significantly. Conclusion: The Glisson pedicle ligation may be an optional treatment in selected cases of unresectable HCC. However, further research is needed to understand the effectiveness of this treatment.

Chemerin enhances the adhesion and migration of human endothelial progenitor cells and increases lipid accumulation in mice with atherosclerosis

BackgroundThe role of adipokines in the development of atherosclerosis (AS) has received increasing attention in recent years. This study aimed to explore the effects of chemerin on the functions of human endothelial progenitor cells (EPCs) and to investigate its role in lipid accumulation in ApoE-knockout (ApoE−/−) mice.MethodsEPCs were cultured and treated with chemerin together with the specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 in a time- and dose-dependent manner. Changes in migration, adhesion, proliferation and the apoptosis rate of EPCs were detected. ApoE−/− mice with high-fat diet-induced AS were treated with chemerin with or without SB 203580. Weights were recorded, lipid indicators were detected, and tissues sections were stained.ResultsThe data showed that chemerin enhanced the adhesion and migration abilities of EPCs, and reduced the apoptosis ratio and that this effect might be mediated through the p38 MAPK pathway. Additionally, chemerin increased the instability of plaques. Compared with the control group and the inhibitor group, ApoE−/− mice treated with chemerin protein had more serious arterial stenosis, higher lipid contents in plaques and decreased collagen. Lipid accumulation in the liver and kidney and inflammation in the hepatic portal area were enhanced by treatment with chemerin, and the size of adipocytes also increased after chemerin treatment. In conclusion, chemerin can enhance the adhesion and migration abilities of human EPCs and reduce the apoptosis ratio. In animals, chemerin can increase lipid accumulation in atherosclerotic plaques and exacerbate plaques instability. At the same time, chemerin can cause abnormal lipid accumulation in the livers and kidneys of model animals. After specifically blocking the p38 MAPK pathway, the effect of chemerin was reduced.ConclusionsIn conclusion, this study showed that chemerin enhances the adhesion and migration abilities of EPCs and increases the instability of plaques and abnormal lipid accumulation in ApoE−/− mice. Furthermore, these effects might be mediated through the p38 MAPK pathway.

Neuroglobin in Neurons of the Frontal and Parietal Cortex of White Rats in Cholestasis

The aim of the study was to investigate the distribution and content of neuroglobin in the pyramidal neurons of the frontal and parietal cortex of white rats during simulated cholestasis.Material and methods. The study included 60 outbred white male rats weighed 200–250 g. Cholestasis was simulated by ligation of the common bile duct in the porta hepatis area (main group, n=30). Animals of the control group (n=30) were performed a false operation preserving physiological bile outflow. Sections of the frontal and parietal cortex of white rats were selected for investigation. The content and distribution of neuroglobin was detected immunohistochemically on paraffin sections using mouse monoclonal primary antibodies Anti- Neuroglobin antibody (Abcam). Cytophotometric analysis was used to perform quantitative assessment of the content of the studied molecular marker; after that statistical analysis was performed.Results. It was found that the content of neuroglobin in the pericarions of neurons of the frontal and parietal cortex modified in a wave-like mode. After ligation of the common bile duct, the content of neuroglobin significantly decreased in 2, 10 and 45 days (minimum on the 10th day) in the frontal cortex and in 90 days in the parietal cortex, and increased in 5 and 20 days of the experiment (maximum on the 20th day).Conclusion. In cholestasis, the content of neuroglobin in the pericarions of neurons of the frontal and parietal cortex modifies in waves: a decrease is observed on the 2nd, 10th, 45th day; an increase is observed on the 5th and 20th day; a recovery is observed on the 90th day.

Effect of Manihot esculenta and Manihot utilissima Cyanide Extract on Some Biochemical Parameters of Albino Rats

Cassava roots (Manihot esculenta and Manihot utilissima) are largely consumed as staple food in African but contain a toxic compound, cyanogenic glycosides. This study evaluated the effect of Manihot esculenta and Manihot utilissima cyanide content on biochemical parameters and histological examination of male albino rats. A total of thirty rats were used for the acute toxicity study while thirty-five rats were used to determine the effect of Manihot esculenta and Manihot utilissima cyanide on biochemical and histological parameters. The results revealed that Manihot esculenta and Manihot utilissima cyanide were toxic to rats even at a lower dose (10 mg/kg body weight) and cause death. Studies on the cyanide concentration determined using the standard curve revealed a high amount of cyanide in Manihot esculenta compared to Manihot utilissima. Biochemical parameters determined include Aspartate transaminases (AST), Alanine transaminases (ALT), Alanine Phosphatase (ALP), Urea, Creatinine, Acid Phosphates, and Lactate Dehydrogenase (LDH). The results revealed a significant (p&lt; 0.05) increase of AST, ALP, Creatinine, Acid Phosphates, and LDH on rats administered with Manihot esculenta cyanide compared to normal rats and Manihot utilissima cyanide while Manihot utilissima cyanide showed significant (p&lt; 0.05) increase on the activity of AST, ALT, ALP, Urea, and Creatinine compared with normal rats. Histological examination of livers and kidneys of the rats revealed that rats administered with Manihot esculenta cyanide showed disruption of the liver and kidney cells with distorted hepatic portal areas and necrosis compared to rats fed with Manihot utilissima cyanide and normal rats. The deleterious effect of the hydrogen cyanide is more pronounced on the tissues of the rats treated with Manihot esculenta as compared to those treated with Manihot utilissima as depicted by the photomicrographs. This study, therefore, concluded that Manihot esculenta is toxic causing alteration on some biochemical and histological parameters, this toxicity was correlated to dysfunction of vital organs which are a reconfirmation of the need for adequate processing of certain food crops prior to consumption. Cassava is a rich source of cyanide, highly documented for its adverse effects on the living system.

Expression of blood hepatocyte-derived microRNA-122 in canine multicentric lymphoma with hepatic involvement.

This study was performed to evaluate the hepatocyte-derived microRNA (miR)-122 as novel diagnostic biomarker in canine lymphoma. Fifteen dogs were enrolled in this study. Dogs presented at Small Animal Teaching Hospital, Faculty of Veterinary Medicine, Cairo University. Dogs were divided into 8 clinically healthy dogs act as control and 7 clinically ill dogs. All dogs were subjected to clinical, ultrasonographic, hemato-biochemical and ultrasound-guided fine-needle biopsy for cytological and histopathological investigations. On the basis of these results, 7 dogs were found to be suffering from multicentric lymphoma involving liver. Serum hepatocyte-derived miRA-122 was determined by real-time quantitative polymerase chain reaction in all dogs. Multicentric lymphoma involving liver manifested by inappetance for several days, depression and peripheral lymphadenopathy. Hematological examination showed significant lymphocytosis. Serum biochemical analysis revealed significant increase in ALT, AST, ALP compared to control dogs. Ultrasonography revealed hypoechoic lymphoid aggregation at area of "porta hepatis" and circumscribed hypoechoic nodule interrupt liver parenchyma. Cytology revealed infiltration of liver tissue by lymphoblast cells and histopathology revealed diffuse infiltration of hepatic sinusoids and portal area by uniform population of small lymphocytes. Serum miRNA-122 analysis showed a significant increase represented as 9.00 fold in canine multicentric lymphoma involving liver. Serum hepatocyte-derived miRNA-122 is of diagnostic value, non invasive, stable and easily measurable blood biomarker for the detection of hepatocellular injury in dogs with multicentric lymphoma involving liver.

Ultrasound differential diagnosis of hepatic hilar cystic lesions in neonates and infants

Objective To explore the value of ultrasound in differential diagnosis of hepatic hilar cyst in neonates and infants. Methods The ultrasonographic characteristics of 93 children with hilar cysts under 6 months of age admitted to the General Surgery Department of Beijing Children′s Hospital.Affiliated to Capital Medical University from January 2014 to December 2018 were retrospectively analyzed.According to the surgical results, they were divided into two groups: cystic biliary atresia (CBA) group and congenital choledochal cyst (CC) group, 21 cases in the CBA group and 72 cases in the CC group.The size of cyst in hepatic portal area, the shape of gallbladder in empty stomach, the expansion of intrahepatic and extrahepatic bile ducts, the deposition of biliary sludge and the communication between cyst and intrahepatic bile duct were observed by ultrasound. Results The cyst volume of CBA group was 0.4(0.1, 1.3)cm3, and that of CC group was 18.3(5.4, 50.3)cm3.The cyst volume of CBA group was significantly smaller than that of CC group (P<0.01); 19 cases had abnormal gallbladder morphology in CBA group and 4 cases in CC group (P<0.01); 1 case had biliary sludge in hilar cyst in CBA group and 51 cases had biliary sludge in cyst in CC group (P<0.01); no intrahepatic bile duct dilatation was observed in CBA group, and 54 cases had intrahepatic bile duct dilatation in CC group (P<0.01); no cyst communicated with intrahepatic bile duct in CBA group, and all cysts communicated with intrahepatic bile duct in CC group (P<0.01). Conclusion Gallbladder shape, cyst size, biliary sludge deposition, intrahepatic bile duct dilatation and the communication between cyst and intrahepatic bile duct can be used as sonographic features to differentiate CBA from CC. Key words: Ultrasound; Cystic biliary atresia; Choledochal cyst

Establishment and Evaluation of Gvhd Mouse Model for Allogeneic Hematopoietic Stem Cell Transplantation

Objective:To study the feasibility of using cyclophosphamide alone without total body irradiation (TBI) as conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and establish a graft-versus-host disease (GVHD) mouse model.Methods:Single cell suspension of spleen and bone marrow were prepared from donor C57/BL/6 mice (B6 mice) . The recipient B6D2F1 mice (F1 mice) were signed into 4 groups with 12 mice per each group. Groups I~III mice were conditioned with peritoneal injection of cyclophosphamide (300 mg/m2/d) on day -5, -4 and -3 of allo-HSCT, and group IV mice were used as control with saline injection. On day 0, group I mice were injected through tail vein with a mixture of 2×107 spleen cells, 5×106 bone marrow cells and 1×104 P815 cells; group II with 5×106 bone marrow cells and 1×104 P815 cells; group III with 1×104 P815 cells and group IV with RPMI1640 culture medium. The blood leukocyte counts were analyzed, GVHD score and the pathological leukemia infiltration of skin, liver and colon were evaluated and compared on day 30 after allo-HSCT.Results:(1) The GVHD scores of group I mice were 2 to 4 on day 14 post allo-HSCT, and mice started to die on day 15, eight (8) mice survived and the GVHD scores of them were 1 to 6 with a survival rate of 66.7% on day 30. Group II mice began to die on day 6 and only one survived on day 30 with a survival rate of 8.3%. All of group III mice died on day 18. Group IV mice survived (Figure 1).(2) The leukocyte counts in group I and group II were significantly increased on day 7 post allo-HSCT(p<0.05). There was also a significant difference in total leukocyte counts between groups I/II and group IV (p<0.05). The leukocyte counts in mice of groups I~III were significantly decreased, and there were a significant difference between group I and groups II/III/IV respectively (p<0.05) on day 14 post allo-HSCT. On day 21 after allo-HSCT, the leukocyte count of Group I and II mice were ≥1×109/L, which means that allo-HSCT were successful. The leukocyte counts in group I mice were again increased on day 28 post allo-HSCT. There was no significant difference between Group I and Group IV (p>0.05).(3) Pathological observation: The cell atrophy and necrosis in the hepatic portal area and slight infiltration of the leukemia cells in central vein were observed in group I recipient mice. The number of hepatocytes of the mice decreased, and the infiltration of the leukemia cells in the liver sinus were observed in group II. The liver was heavily infiltrated by leukemic cells in group III mice. The mouse livers were normal in group IV mice.Conclusion:It is feasible to establish GVHD model of the leukemia mice with cyclophosphamide conditioning regimen of allo-HSCT, and simple to operate. This is less harmful to people, animals and the environment.Discussion:The traditional animal model of GVHD is based on TBI conditioning regimen prior to allo-HSCT. However, the process can lead to systemic adverse reactions such as myelosuppression, radiation gastroenteritis, endocrine disorders and systemic function disorders, etc. in both the operators and animals. Therefore, the radiotherapy doses have to be low. At the same time, it is difficult to establish animal models of GVHD due to the uneven distribution of the doses. Cyclophosphamide was selected for the conditioning regimen of allo-HSCT in the study. Cyclophosphamide had the effect direct on killing tumor cells, induced recipients to tolerate the immune of donors, enabled to implant donor cells into recipients smoothly. The stable chimeras were obtained. There are a large number of T and B lymphocytes in donor's spleen cells. By injecting donor spleen cells and active immune cells derived from proliferation and differentiation of hematopoietic stem cells, the effects of graft-anti-leukemia are availably activated in recipients.AcknowledgmentsWe thank Dr Zhifu Xiang very much for his great helpful revisions. DisclosuresNo relevant conflicts of interest to declare.

Preliminary test on the distribution, hydrolyzation and excretion of aluminum dialkyl phosphinate flame retardants in rats

Aluminum dialkyl phosphinates (ADPs) are a promising class of chemicals offering superior flame retardance. However, knowledge on their behavior in vivo is scarce. Hydrolysis has been suggested as one of the major routes of environmental degradation of ADPs. Herein, aluminum methylcyclohexyl phosphinic (AMHP), a kind of ADPs with industrial production in China, and its hydrolysate methyl cyclohexyl phosphinic acid (MHPA) were continuously exposed to Sprague Dawley (SD) rats for 28 days in this study. The same ratio of MHPA in organs to serum and the same daily excretion of MHPA were observed for AMHP exposure group and MHPA exposure group, suggesting the hydrolysis of AMHP in vivo. The hydrolysis of AMHP to MHPA was further confirmed by in vitro simulated human gastric intestinal juice. Therefore, both AMHP and MHPA distributed in liver, kidney and even brain in the form of MHPA. More than 80% of AMHP and MHPA could be excreted by feces and urine. Feces are the main route of excretion of AMHP and MHPA. The denseness of the inflammatory cell in the hepatic portal area and biochemical indexes showed the obvious dose-effect relationship. However, the toxicity of AMHP and MHPA was quite low even with exposure level up to 100 mg/kg dw/day. The low cumulative ability and mild toxicity indicated AMHP as a promising substitute for brominated flame retardant.

DUNALIELLA SALINA IMPROVED OBESITY-ASSOCIATED INFLAMMATION AND OXIDATIVE DAMAGE IN ANIMALS’ RODENT

Objective: The objective of this study is to investigate the efficacy of microalgae Dunaliella salina to improve apelin, oxidative damage, inflammatory, and apoptotic function implicated in high-fat diet (HFD)-induced obesity in rats.Methods: Fifty male Westar albino rats weighing 150–160 g were fed on HFD for 12 weeks. Treatment of obese rats with D. salina was carried out in a dose 150 mg/kg body weight as compared to orlistat as anti-obesity standard drug. Blood nuclear factor kappa-B cells (NF-kB), apelin, apoptosis regulator (B-cell lymphoma 2 [BCl2]), monocytes chemo attractant protein-1, paraoxonase-1 (PON1) were determined in serum of different groups. Besides, lipid peroxidation (malondialdehyde [MDA]), glutathione (GSH) levels as well as histopathological examination were investigated in liver tissue of obese rats.Results: Serum apelin, MDA, and NF-kB levels were significantly high, reached to 97.25, 158.18, 511.433, and 170.73%, respectively. While significant decrease in PON1 (47.82%), BCl2 (74.88%), and GSH (63.54 %), levels were detected in the obese rats compared to controls. Obviously improvement in all biomarkers under investigation upon treated obese rats with ethanol extract of D. salina. Histopathological examination of obese hepatic tissue showed dilatation in the central portal veins associated with inflammatory cells infiltration in the portal area and congestion. However, treatment of obese rats with D. salina confirmed biochemical analysis and declared less diffuse inflammatory cells infiltration as well as less focal infiltration in both hepatic parenchyma and portal area with higher improvement in D. salina than drug.Conclusion: It could be concluded that D. salina has a great ability to improve inflammation associated with obesity as well as damaged hepatic architectures which can be used as a promising anti-obesity nutraceuticals.

TB of Porta Hepatis Presenting With Obstructive Jaundice: A Case Report

Introduction: Mycobacterium Tuberculosis causes tuberculosis. The number of reported TB cases in United States has been decreasing each year in the last 2 decades. Extra pulmonary TB can present anywhere in the body, however isolated peri-pancreatic or hepatobiliary TB is rare. Case Report: 25-year-old Pakistani immigrant male presented with 2 weeks of vague RUQ pain, pruritus, fever, nausea, acolic stool and dark urine. On exam: RUQ abdominal tenderness, yellow skin discoloration. AST 107 IU/L, ALT 211 IU/L, ALP 273 IU/L, LDH 214 IU/L, total bilirubin 11.4 mg/dl, indirect bilirubin 4 mg/dl, direct bilirubin 7.4 mg/dl. US showed a mass in the pancreatic area. CT showed a 5.5x4.1x4.8 cm complex cystic mass in the region of Porta Hepatis with resultant intrahepatic biliary dilatation that extends to the level of mass as well as 1.4 cm intra-aortocaval lymph node. Emergency ERCP with biliary stent placement was performed. FNA of the intra-aortocaval lymph node was performed. Biopsy: granulomatous inflammation, negative for malignant cells, fungal or AFB stains; the PCR positive for M. Tuberculosis DNA. CT chest: bulky non-calcified right Para-tracheal lymph node (1.5x2.7 cm). Mediastinoscopy was performed with lymph node biopsy: granulomatous inflammation, stains for AFB and fungi negative, PCR positive for M.Tuberculosis. T spot TB test was positive. Patient improved with stent placement and started on Isoniazid, Rifampin, Pyrazinamide and Ethambutol (2 months), followed by INH and Rifampin (4 months). Follow up imaging: complete resolution of the porta hepatis mass and lymph nodes. Discussion; Abdominal TB presents in one or more of the following forms: tuberculous lymphadenopathy, peritoneal tuberculosis, GI tract tuberculosis and visceral tuberculosis. Abdominal TB can occur due to hematogenous route, inhaling the tuberculosis spores, tubercular focus can develop in the lung from which hematogenous spread to other body parts takes place or ingestion of bacteria and then translocation across the intestinal wall. Diagnosis is made by demonstration of granulomas or AFB on Zeil-Neelson stain (low diagnostic value). PCR can effectively detect mycobacterium DNA in tissue sample. Early treatment with Quadruple therapy can effectively treat abdominal TB. Conclusion: Porta hepatis TB diagnosis is challenging and often confused with malignancy with high mortality risk if left untreated. Clinical outcome improves significantly with anti-Tuberculosis drugs.Figure: CT Abdomen, axial section, showing mass in porta hepatis area.Figure: CT abdomen, coronal section, showing mass in porta hepatis area with resultant intrahepatic biliary dilatation.Figure: CT abdomen, axial section, showing CBD stent with resolution of porta hepatis mass.

Energy restriction affect liver development in Hu sheep ram lambs through Hippo signaling pathway.

This study aimed to evaluate the effects of dietary energy restriction on postnatal liver development in Hu sheep ram lambs. A total of 16 ram lambs were randomly divided into two groups: 100% energy requirements diet and 55% energy requirements diet, which were fed for 75 d. Results showed that the final body and liver weights decreased with energy restriction (p <0.05). Energy restriction caused a significant decrease in the levels of circulating insulin-like growth factor 1 (IGF1) and an increase in growth hormone secretion (p <0.05), which can be explained by the decreased mRNA expression levels of the growth hormone receptor (GHR) and IGF1 (p <0.05). The proliferating cell nuclear antigen (PCNA), Ki-67 and apoptosis-related proteins (BAX and BCL2) were mainly located in the nucleus and the cytoplasm of hepatocytes, respectively. The transcription and protein levels of PCNA and BAX were significantly decreased and increased by energy restriction, respectively (p <0.05). The caspase9 and caspase3 mRNA and activity were increased in energy restriction group (p <0.05). Moreover, Hippo signaling pathway proteins [mammalian sterile 20-like protein kinase 1 (MST1), large tumor suppressor kinase 1 (LATS1), and yes-associated protein 1 (YAP1)] were mainly observed around the hepatic portal area, and the expression levels of their mRNA and proteins were significantly decreased in energy restriction group (p <0.05). In summary, energy restriction in ram lambs impairs liver development by increasing apoptosis, which may occur via the Hippo signaling pathway.

Effectiveness of hepatic parenchyma lithotomy of hepatolithiasis: A single-center experience.

To investigate the clinical significance of hepatic parenchyma incision by lithotomy near the second hepatic portal area for the treatment of complex hepatolithiasis.A retrospective study was conducted with 35 patients who had complicated hepatolithiasis in our hospital from January 2008 to December 2013, who underwent hepatic parenchyma incision by lithotomy near the second hepatic portal area. The perioperative and long-term outcomes included the stone clearance rate, operative morbidity and mortality, and the stone recurrence rate. Patients with a preoperative diagnosis of cholangiocarcinoma were excluded from the study.All patients with hepatic duct stones were mainly located at S2, S4, and S8 regions. Surgical methods included were hepatic parenchyma incision by lithotomy near the second hepatic portal area, or by combined partial hepatectomy. The mean follow-up period was 51 months. One patient died during hospitalization. The surgical morbidity was 17.6%, stone clearance rate was 88.2%, and final clearance rate was 94.1% followed by postoperative choledochoscopic lithotripsy. The stone recurrence rate was 15.6% and the occurrence of postoperative cholangitis was 11.8% during the follow-up period.Hepatic parenchyma incision by lithotomy near the second hepatic portal area is safe with satisfactory short and long-term outcome results for complicated hepatolithiasis.

Planimetry of the porta hepatis in biliary atresia.

Orientation and digital analysis of the biliary remnants in the resected porta hepatis in infants with biliary atresia. Samples were orientated intra-operatively then stained with haematoxylin and eosin and immunostained for cytokeratin 7 (CK7). Sections were then digitized and analysed. Most proximal transected surface area was defined as the porta hepatis area (PHA) and the biliary epithelial area was defined as 'BEA'. Data are quoted as median (range). Non-parametric statistical comparisons were made as appropriate. P < 0.05 was regarded as significant. Thirty-eight infants underwent surgery [median age 53 (16-120) days]. Eight specimens were excluded from the study due to technical reasons, leaving 30 specimens as the study cohort. Median PHA was 70 (30-133) mm2 , median BEA 0.57 (0.07-5.5) mm2 (r = 0.51; P < 0.002). The median BEA/PHA ratio was 9.6 × 10-3 (1.9-104 × 10-3 ). There was a marked correlation of PHA with plasma γ-glutamyl transpeptidase (r = -0.51; P = 0.001). Both total BEA and the BEA/PHA ratio correlated with alkaline phosphatase (r = -0.35; P = 0.03 and r = -0.47; P = 0.005, respectively). Age at surgery correlated inversely with BEA (r = -0.44; P = 0.01) but not PHA (P = 0.1). Precise quantification of biliary remnants is possible and correlates with biochemical variables. Values for BEA were associated with and declined demonstrably with increasing age at surgery.

Application of liver visualization technologies in hilar tumor resection at the second hepatic portal area

To discuss the application of liver visualization technology in complex liver tumor resection at the second hepatic portal area. Clinical data of 80 cases who received surgery at the second hepatic portal area from August 2014 to September 2015 in the Third Department of Hepatic Surgery of Eastern Hepatobiliary Surgery Hospital were analyzed retrospectively. There were 58 male and 22 female patients aged from 21 to 70 years with median age of 52 years. Median maximum diameter of tumor was 7.6 cm (3.0 to 17.0 cm). Before surgery, liver dimensional graphics produced by liver visualization technology were taken on all patients to observe the relationship between intrahepatic vasculars and the liver tumor, and to calculate the intended resection range and the remaining liver volume in order to make a proper surgery plan. Suitable hepatic vascular occlusion was applied in the tumor resection. Intrahepatic vessel shape and variation, surgical operation, surgical operation time, manner and time of hepatic vascular occlusion, blood loss, liver resection volume, postoperative complications were observed. There were 23 patients who changed surgery plan after liver visualization technology.There were 44 cases with single main hepatic vein compressed by tumors, 32 cases with 2 main hepatic veins, 4 cases with 3 main hepatic veins compressed by tumors.And there were 58 cases with both hepatic vein and inferior vena cava compressed by tumor. Hepatic segments 6 and 7 was removed in 12 cases, 14 cases, hepatic segments 4, 5 and 8 were removed in 8 cases.Right hepatectomy was carried out in 9 patients and left hepatectomy was carried out in 8 patients. Right trisectionectomy was carried out in 3 patients and left trisectionectomy was applied in 5 patients.Local hepatectomy was performed in 12 patients. Nine patients received associating liver partition and portal vein ligation for staged hepatectomy. Four patients underwent total hepatic vascular exclusion, while 16 patients underwent selective hepatic vascular exclusion. The median surgical time was 132 minutes(80 to 240 minutes). Median blood loss volume was 580 ml(100-5 000 ml). Median volume of hepatic resection was 750 ml(30 to 2 000 ml). One patient needed secondary surgery to stop bleeding as a result of postoperative abdominal bleeding.Complication of postoperative bile leakage occurred in 14 cases.Five patients had pleural effusion requiring invasive therapy.Four patients had ascites requiring invasive therapy. Besides, 5 patients had incisive infection while 2 patients were found with pulmonary infection after surgery and two patients occurred biliary obstruction. There was no death case occurred a result of surgery. Using liver visualization technology to make surgical operation plan can improve surgical safety of the second hepatic portal area and optimize the operation plan. It can also reduce the risk of blood loss and postoperative complications such as liver failure.

Neural effects of gut- and brain-derived glucagon-like peptide-1 and its receptor agonist.

Glucagon‐like peptide‐1 (GLP‐1) is derived from both the enteroendocrine L cells and preproglucagon‐expressing neurons in the nucleus tractus solitarius (NTS) of the brain stem. As GLP‐1 is cleaved by dipeptidyl peptidase‐4 yielding a half‐life of less than 2 min, it is plausible that the gut‐derived GLP‐1, released postprandially, exerts its effects on the brain mainly by interacting with vagal afferent neurons located at the intestinal or hepatic portal area. GLP‐1 neurons in the NTS widely project in the central nervous system and act as a neurotransmitter. One of the physiological roles of brain‐derived GLP‐1 is restriction of feeding. GLP‐1 receptor agonists have recently been used to treat type 2 diabetic patients, and have been shown to exhibit pleiotropic effects beyond incretin action, which involve brain functions. GLP‐1 receptor agonist administered in the periphery is stable because of its resistance to dipeptidyl peptidase‐4, and is highly likely to act on the brain by passing through the blood–brain barrier (BBB), as well as interacting with vagal afferent nerves. Central actions of GLP‐1 have various roles including regulation of feeding, weight, glucose and lipid metabolism, cardiovascular functions, cognitive functions, and stress and emotional responses. In the present review, we focus on the source of GLP‐1 and the pathway by which peripheral GLP‐1 informs the brain, and then discuss recent findings on the central effects of GLP‐1 and GLP‐1 receptor agonists.

Biliary fibrosis drives liver repopulation and phenotype transition of transplanted hepatocytes

Current research focuses on developing alternative strategies to restore decreased liver mass prior to the onset of end-stage liver disease. Cell engraftment/repopulation requires regeneration in normal liver, but we have shown that severe liver injury stimulates repopulation without partial hepatectomy (PH). We have now investigated whether a less severe injury, secondary biliary fibrosis, would drive engraftment/repopulation of ectopically transplanted mature hepatocytes. Ductular proliferation and progressive fibrosis in dipeptidyl-peptidase IV (DPPIV)(-) F344 rats was induced by common bile duct ligation (BDL). Purified DPPIV(+)/green fluorescent protein (GFP)(+) hepatocytes were infused without PH into the spleen of BDL rats and compared to rats without BDL. Within one week, transplanted hepatocytes were detected in hepatic portal areas and at the periphery of expanding portal regions. DPPIV(+)/GFP(+) repopulating cell clusters of different sizes were observed in BDL rats but not untreated normal recipients. Surprisingly, some engrafted hepatocytes formed CK-19/claudin-7 expressing epithelial cells resembling cholangiocytes within repopulating clusters. In addition, substantial numbers of hepatocytes engrafted at the intrasplenic injection site assembled into multicellular groups. These also showed biliary "transdifferentiation" in the majority of intrasplenic injection sites of rats that received BDL but not in untreated recipients. PCR array analysis showed upregulation of osteopontin (SPP1). Cell culture studies demonstrated increased Itgβ4, HNF1β, HNF6, Sox-9, and CK-19 mRNA expression in hepatocytes incubated with osteopontin, suggesting that this secreted protein promotes dedifferentiation of hepatocytes. Our studies show that biliary fibrosis stimulates liver repopulation by ectopically transplanted hepatocytes and also stimulates hepatocyte transition towards a biliary epithelial phenotype.