Clinical characteristics and management of orbital apex syndrome: a 10-year multicentre experience.

BACKGROUND: Orbital apex syndrome (OAS) is a condition characterised by lesions within the orbital apex, leading to various ophthalmologic symptoms. This study aimed to analyse the clinical characteristics and treatment strategies of OAS with respect to aetiology. METHODS: This retrospective analysis utilised data from 5 medical institutions between 2013 and 2022. Patients who were diagnosed with OAS were initially enrolled, but patients who failed to follow up at least 1 month were excluded. The prevalence of initial ophthalmologic symptoms and visual improvement after treatment was compared according to aetiology. Factors related to visual improvement were analysed. RESULTS: Among 73 enrolled patients, the leading aetiology was tumours, followed by fungal infections and inflammation. Visual impairment and proptosis were prevalent in tumour-related OAS cases. Inflammation-related OAS exhibited a higher likelihood of painful eye movements and ophthalmoplegia. Ptosis was most frequently observed in fungal infection-related OAS. Notably, fungal infections emerged as the sole significant factor negatively impacting vision progression. In inflammation-related OAS, the time interval between symptom onset and the administration of steroids was longer in patients without visual improvement, even though there was no statistically significant difference. CONCLUSIONS: Tumours were the predominant cause of OAS. Visual impairment was a common manifestation in tumour-related OAS, while fungal infections were strongly associated with a poor visual prognosis. The timely administration of steroids might be helpful for improving vision in patients with inflammation-related OAS. However, further studies are needed to enhance understanding and management of OAS.

Transient hexagonal structures in sheared emulsions of isotropic inclusions on smectic bubbles in microgravity conditions.

We describe the collective behavior of isotropic droplets dispersed over a spherical smectic bubble, observed under microgravity conditions on the International Space Station (ISS). We find that droplets can form two-dimensional hexagonal structures changing with time. Our analysis indicates the possibility of spatial and temporal periodicity of such structures of droplets. Quantitative analysis of the hexagonal structure including the first three coordination circles was performed. A peculiar periodic-in-time ordering of the droplets, related to one-dimensional motion of droplets with non-uniform velocity, was found.

Amino acid digestibility in corn distillers' dried grains with solubles in pigs at different dietary levels of casein and test ingredient.

Digestibility of amino acids (AA) in feed ingredients for pigs has been generally determined by feeding experimental diets containing test feedstuffs as a sole source of N, which may lead to the deficiency or imbalance of AA and hinder an accurate determination of digestibility values. Therefore, the addition of casein in experimental diets may ameliorate the potential negative effects of deficiency or imbalance of AA. In addition, the concentration of test feedstuffs in experimental diets may affect the digestibility of AA in test feedstuffs. Two experiments were conducted with corn distillers' dried grains with solubles (DDGS) as the test feedstuff to determine the effects of increasing concentrations of casein in experimental diets on standardized ileal digestibility (SID) of AA in DDGS (experiment 1) and to investigate the effects of two concentrations of DDGS in experimental diets with or without the addition of casein on SID of AA in DDGS (experiment 2). In experiment 1, 20 barrows (initial BW = 45.3 ±â€¯1.80 kg) surgically fitted with T-cannulas at the distal ileum were allocated to a quadruplicate 5 × 2 incomplete Latin square design with five diets and two periods. Four isonitrogenous diets containing increasing concentrations of casein from 0 to 165 g/kg with decreasing concentrations of DDGS from 466.8 to 0 g/kg and a N-free diet were prepared. The SID of AA, except for arginine, cysteine, and glycine, in DDGS linearly decreased (P < 0.05) with increasing concentrations of casein in experimental diets. Quadratic response (P = 0.023) was observed in the SID of lysine in DDGS when the concentration of casein in experimental diets increased. In experiment 2, the same 20 barrows (initial BW = 52.8 ±â€¯2.99 kg) and experimental design as experiment 1 were used with different diets, which were prepared as a 2 × 2 factorial arrangement with the concentration of DDGS at 466.8 or 155.6 g/kg and that of casein at 0 or 110 g/kg. Regardless of the addition of casein, pigs fed experimental diets containing 466.8 g/kg DDGS had greater (P < 0.01) SID of indispensable AA, except for tryptophan, in DDGS than those fed diets containing 155.6 g/kg DDGS. In conclusion, the addition of casein in experimental diets did not affect the SID of AA in DDGS, whereas the SID of AA in DDGS decreased as the concentration of DDGS in diets decreased.

Additivity of apparent and standardized ileal digestibility of phosphorus in mixed diets containing corn and soybean meal fed to broiler chickens.

Phosphorus (P) is an integral part of diet formulation for broiler chickens as P is required for various biochemical processes essential to life. A study was designed to examine the additivity of apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of P in mixed diets containing corn and soybean meal (SBM) with or without phytase supplementation. Birds were fed a commercial starter diet from day 0 to 21 after hatching and then allotted to 7 dietary treatments in a randomized complete block design with the BW as a blocking factor. Four semipurified diets were prepared to contain corn or SBM as the sole source of P with or without the addition of phytase at 1,000 phytase units/kg of diet. Two mixed diets were also prepared to contain corn and SBM with or without the addition of phytase at 1,000 phytase units/kg diet. A P-free diet (PFD) was formulated to determine the basal ileal endogenous loss of P. There were 16 replicate cages of the PFD and 8 replicate cages of the 6 experimental diets, with 8 birds per replicate cage for a total of 512 birds. Diets were fed for 3 d. The ileal digesta of birds were collected from the distal two-thirds of the ileum on day 24 after hatching. The SID of P in corn and SBM were 52.2 and 65.4%, respectively (SEM = 1.37). The addition of phytase improved (P < 0.05) both the AID and SID of P in the corn, SBM, and mixed diets. The determined AID or SID in the corn and SBM with or without phytase was used to predict the AID or SID in the mixed diets. There were no differences between the predicted and determined digestibility values in the mixed diets for either AID or SID of P and thus additive. Phytase supplementation of the mixed diet did not influence the additivity of AID or SID. In conclusion, the AID or SID of P in the corn and SBM was additive in the mixed diets containing corn and SBM with or without the addition of phytase.

Hepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans.

African Americans (AAs) are an admixed population with widely varying proportion of West African ancestry (WAA). Here we report the correlation of WAA to gene expression and DNA methylation in AA-derived hepatocytes, a cell type important in disease and drug response. We perform mediation analysis to test whether methylation is a mediator of the effect of ancestry on expression. GTEx samples and a second cohort are used as validation. One hundred and thirty-one genes are associated with WAA (FDR < 0.10), 28 of which replicate and represent 220 GWAS phenotypes. Among PharmGKB pharmacogenes, VDR, PTGIS, ALDH1A1, CYP2C19, and P2RY1 nominally associate with WAA (p < 0.05). We find 1037 WAA-associated, differentially methylated regions (FDR < 0.05), with hypomethylated genes enriched in drug-response pathways. In conclusion, WAA contributes to variability in hepatocyte expression and DNA methylation with identified genes previously implicated for diseases disproportionately affecting AAs, including cardiovascular (PTGIS, PLAT) and renal (APOL1) disease, and drug response (CYP2C19).

Clinical features and prognosis of patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) share common risk factors. They could therefore be expressed in a single patient. However, the prevalence, clinical characteristics and prognosis of individuals with comorbid IPF and COPD are not known. From 2003 to 2007, the Korean Interstitial Lung Disease Study Group created a register for idiopathic interstitial pneumonia using 2002 ATS/ERS (American Thoracic Society/European Respiratory Society) criteria. Of the 1546 IPF patients assessed, 143 had decreased lung function consistent with COPD (IPF-COPD). COPD was diagnosed based on age (≥40 years) and pulmonary function (forced expiratory volume in 1 sec [FEV1]/forced vital capacity [FVC] ratio < 0.7). The median age of the IPF-COPD group was 71.0 years (interquartile range 66.0-76.0); most patients were male (88.1%). FVC (%) was significantly higher in the IPF-COPD group; however, FEV1 (%) was significantly lower in the IPF-COPD group (P < 0.001). Diffusing capacity of the lung for carbon monoxide (DLCO) was not significantly different between the two groups. In survival analysis, age and FVC (%), but not COPD, were significantly associated with prognosis (respectively P = 0.003, 0.001 and 0.401). COPD severity was also not related to prognosis (P = 0.935). The prevalence of IPF-COPD was estimated to be ∼9.2% among all IPF patients; prognosis of patients with IPF-COPD was not worse than those with IPF alone. .

Intraoperative Management to Prevent Cardiac Collapse in a Patient With a Recurrent, Large-volume Pericardial Effusion and Paroxysmal Atrial Fibrillation During Liver Transplantation: A Case Report.

BACKGROUND: Pericardial effusion is a common feature of end-stage liver disease. In this case report we describe the intraoperative management of recurrent pericardial effusion, without re-pericardiocentesis, to prevent circulatory collapse during a critical surgical time-point; that is, during manipulation of the major vessels and graft reperfusion. METHODS: A 47-year-old woman with hepatitis B was scheduled to undergo deceased donor liver transplantation (LT). A large pericardial effusion was preoperatively identified using transthoracic echocardiography (TTE). The patient also had paroxysmal atrial fibrillation. Two days before surgery, preemptive pericardiocentesis was performed and the 1150-mL effusion was drained. Intraoperatively, recurrence of the large pericardial effusion was identified using transesophageal echocardiography (TEE). During inferior vena cava manipulation, the surgeon consulted the anesthesiologist to evaluate the hemodynamic changes in the patient. After 3 attempts, the transplant team was able to determine the most appropriate anastomosis site, defined as that with the least impact on cardiac function. To prevent the development of severe postreperfusion syndrome, 10% MgSO4 (2 g) was gradually infused 20 minutes before portal vein declamping, and immediately before graft reperfusion a 100-µg bolus of epinephrine was administered. RESULTS: During graft reperfusion, there was no evidence of heart chamber collapse or flow disturbance, as seen on the TEE findings. Postoperatively, the patient recovered completely and was discharged from the hospital. Six months after surgery, there was no sign of pericardial effusion on follow-up TTE. CONCLUSION: Our intraoperative strategy may prevent cardiac collapse in patients with pericardial effusion detected during LT. Intraoperative TEE plays an important role in guiding hemodynamic management.

Perioperative Changes in the Psoas Muscle Index in Patients Undergoing ABO-Incompatible Living-Donor Liver Transplantation: A Single-Center Experience.

INTRODUCTION: In the era of rituximab, ABO-incompatible living-donor liver transplantation (ABOi LDLT) is clinically accepted as a feasible therapy for end-stage liver disease. To date, no data on postoperative sarcopenic changes in patients undergoing ABOi LDLT are available. PATIENTS AND METHODS: Thirty-six adult patients undergoing ABOi LDLT between October 2010 and July 2017 at our hospital were retrospectively analyzed. The cross-sectional areas of both psoas muscles between the third and fourth lumbar vertebrae were manually estimated from abdominal computed tomography images obtained within 1 month before surgery, and 1 and 3 weeks, 6 months, and 1 year after surgery. The mean psoas muscle areas were calculated and normalized by the height squared to create psoas muscle indices (PMIs). RESULTS: The PMIs on postoperative days (PODs) 7 and 21 were significantly lower than the preoperative PMI in each whole study and male cohort. In whole study cohort, the absolute and relative PMIs on POD 7 were 308.8 (271.5-375.8) mm2/m2 and 95.3% (89.9%-101.1%). On POD 21, the values were 297.8 (258.5-349.6) mm2/m2 and 90.7% (81.1%-99.2%). In men, they were 335.3 (276.7-389.4) mm2/m2 and 94.2% (89.0%-98.8%) on POD 7, and 305.0 (271.6-357.0) mm2/m2 and 89.2% (83.2%-98.2%) on POD 21. In women, they were 281.2 (231.1-313.7) mm2/m2 and 101.4% (95.2%-106.0%) on POD 7, and 260.7 (245.9-273.9) mm2/m2 and 98.9% (77.9%-124.3%) on POD 21. CONCLUSION: Patients undergoing ABOi LDLT were most vulnerable to core muscle loss soon after surgery.

Intraoperative Management of a Patient With Impaired Cardiac Function Undergoing Simultaneous ABO-Compatible Liver and ABO-Incompatible Kidney Transplant From 2 Living Donors: A Case Report.

BACKGROUND: Combined liver and kidney transplant is a very complex surgery. To date, there has been no report on the intraoperative management of patients with impaired cardiac function undergoing simultaneous ABO-compatible liver and ABO-incompatible kidney transplant from 2 living donors. CASE REPORT: A 60-year-old man underwent simultaneous ABO-compatible liver and ABO-incompatible kidney transplant from 2 living donors because of IgA nephropathy and alcoholic liver cirrhosis. The preoperative cardiac findings revealed continuous aggravation, shown by large left atrial enlargement, severe left ventricular hypertrophy, a very prolonged QT interval, and a calcified left anterior descending coronary artery. Severe hypotension with very weak pulsation and severe bradycardia developed, with an irregular junctional rhythm noted immediately after the liver graft was reperfused. Although epinephrine was administered as a rescue drug, hemodynamics did not improve, and central venous pressure and mean pulmonary arterial pressure increased to potentially fatal levels. Emergency phlebotomy via the central line was performed. Thereafter, hypotension and bradycardia recovered gradually as the central venous pressure and mean pulmonary arterial pressure decreased. The irregular junctional rhythm returned to a sinus rhythm, but the QTc interval was slightly more prolonged. Because of poor cardiac capacity, the volume and rate of fluid infusion were increased aggressively to maintain appropriate kidney graft perfusion after confirming vigorous urine production of the graft. CONCLUSIONS: A heart with impaired function due to both end-stage liver and kidney diseases may be less able to withstand surgical stress. Further study on cardiac dysfunction will be helpful for the management of patients undergoing complex transplant surgery.

Tetrahydrocurcumin Ameliorates Tacrolimus-Induced Nephrotoxicity Via Inhibiting Apoptosis.

BACKGROUND: Calcineurin inhibitors are effective immunosuppressive agents, but associated adverse effects such as nephrotoxicity may limit efficacy. Tacrolimus (FK506) is an immunosuppressive drug used mainly to lower the risk of organ rejection after allogeneic organ transplant. Adverse effects of FK-506 can prompt patients to end treatment despite the efficacy. In the present study, we investigated the protective effect and mechanism of tetrahydrocurcumin (THC) on FK506-induced renal damage, apoptosis, and oxidative stress to evaluate its possible use for kidney protection. MATERIALS AND METHODS: The effect of THC on FK506-induced kidney cell damage was investigated in LLC-PK1 cells. LLC-PK1 cells were pretreated with THC at concentrations of dose for 2 hours followed by addition of FK506 for 24 hours. LLC-PK1 cells were treated with FK506 and THC, and cell viability and glutathione was measured. The number of apoptotic cells was measured using an annexin V/propidium iodide staining with flow cytometry. The effect of apoptosis by THC in LLC-PK1 cells was determined by measuring the caspase-9, caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein levels using Western blotting analyses. RESULTS: FK506-induced LLC-PK1 renal cell damage was markedly ameliorated by THC treatment. THC protected LLC-PK1 cells by preventing FK506-induced glutathione decrease. THC protects against FK506-induced apoptosis in LLC-PK1 cells. Apoptosis was significantly decreased, and Bcl-2 was elevated in the THC-treated group. Bcl-2-associated X protein, caspase-3, and caspase-9 were decreased in the THC-treated group. CONCLUSION: These results collectively provide therapeutic evidence that THC ameliorates the FK506-induced renal damage via antioxidant effect and apoptosis inhibition.

Comparison of amino acid digestibility in full-fat soybean, two soybean meals, and peanut flour between broiler chickens and growing pigs.

The aim of this study was to determine the apparent ileal digestibility (AID) and the standardized ileal digestibility (SID) of CP and AA in full-fat soybean (FFSB), solvent-extracted soybean meal containing 430 g/kg CP (SBM-43), solvent-extracted soybean meal containing 470 g/kg CP (SBM-47), and peanut flour (PNF) fed to broiler chickens and pigs and to compare the digestibility of CP and AA between broiler chickens and pigs. Four diets were prepared to contain FFSB, SBM-43, SBM-47, and PNF as the sole source of N. A N-free diet was formulated to estimate the basal ileal endogenous losses of CP and AA for broiler chickens and pigs. In Exp. 1, a total of four hundred sixteen 21-d-old male broiler chickens (922.1 ± 79.9 g initial BW) were assigned to 5 experimental diets in a randomized complete block design with BW as a blocking factor. After 5 d of adaptation, ileal digesta samples were collected after birds were euthanized by CO asphyxiation. In Exp. 2, twenty barrows (62.0 ± 6.9 kg initial BW) surgically fitted with T-cannulas at the distal ileum were allotted to 5 experimental diets with 2 consecutive 7-d experimental periods. After 5 d of adaptation, ileal digesta samples were collected at d 6 and 7. For statistical analysis, treatments were considered a 2 × 4 factorial arrangement with effects of species and experimental diets (Exp. 1 vs. Exp. 2). There were no interactions between species and diets for the digestibility of CP and AA except for Cys ( < 0.01). The AID of CP and indispensable AA in pigs were greater ( < 0.01) than in broiler chickens. In both broiler chickens and pigs, the AID of CP and indispensable AA in SBM-47 were greater ( < 0.05) than in FFSB, and the AID of Lys in PNF was the least ( < 0.05) among ingredients. The SID of CP and indispensable AA in pigs were greater ( < 0.05) than in broiler chickens except for Trp. In both broiler chickens and pigs, the SID of Lys in PNF was the least ( < 0.05) among ingredients. In broiler chickens, the SID of CP, Ile, Leu, Thr, Trp, and Val in FFSB were less ( < 0.05) than that in SBM-43, SBM-47, and PNF. In pigs, the SID of Arg, Ile, Leu, Met, Phe, and Val in FFSB were less ( < 0.05) than in SBM-43, SBM-47, and PNF. In conclusion, the digestibility of CP and most AA were less in broiler chickens than in pigs, but the pattern of differences in the AA digestibility among ingredients was similar between broiler chickens and pigs.

Generating equations to estimate body mass of Korean skeletal remains.

ABSTRACT: This study aims to generate Korean specific standards for body mass estimation and compare their performance to previous techniques derived from non-Korean samples. Due to a lack of known reference samples in Korea, estimation equations were generated using the hybrid method on 106 Korean unknown skeletons. In the first phase of the hybrid method (morphometric method), a downward adjustment of 4.5 kg was necessary to compensate for a systematic overestimation associated with the morphometric method being applied to Asian samples. Estimates using the adjusted morphometric method were regarded as actual body mass. New body mass equations revealed a better performance in accuracy and precision than previous techniques. However, caution is required in their forensic application because they yield an estimate for body mass around onset of adulthood, rather than the body mass at the time of death.

Lactococcus lactis KR-050L inhibit IL-6/STAT3 activation.

AIMS: The purpose of this study was to investigate IL-6/STAT3 inhibitory activity using lactic acid bacteria (LABs) isolated from Gajuknamu kimchi. METHODS AND RESULTS: Six LABs were isolated from Gajuknamu kimchi and identified through 16S rRNA sequencing. Among them, the culture broth of Lactococcus lactis KR-050L inhibited IL-6-induced STAT3 luciferase activity. Fifteen compounds were isolated from the EtOAc extract of culture broth though column chromatography and preparative high-performance liquid chromatography, and they were identified as 2,5-diketopipperazine structures by spectroscopic analyses (MS, 1 H- and 13 C-NMR). They also showed inhibitory activities on IL-6-induced STAT3 activation, and showed the different in activity according to the presence of a phenylalanine residue, hydroxyl groups and isometric structure. CONCLUSIONS: The six new LABs isolated from Gajuknamu kimchi, and Lc. lactis KR-050L was selected as candidate IL-6/STAT3 inhibitors. The activity levels of 15 2,5-DKPs isolated from Lc. lactis KR-050L were verified. SIGNIFICANCE AND IMPACT OF THE STUDY: This study constitutes the first attempt to isolate various LABs from Gajuknamu kimchi and to discover IL-6/STAT3 inhibitors in the EtOAc extract of Lc. lactis KR-050L culture broth. Moreover, our data provide useful biochemical information regarding the commercialization of Lc. lactis isolated from Gajuknamu kimchi as an approach to use functional foods for the treatment of various diseases via IL-6/STAT3 activation.

Navigation programs, are they helpful for perioperative care with thyroid cancer patients?

The purpose of this study was to develop and evaluate a navigation program for patients with thyroid cancer. The navigation program was developed following an analysis of the unmet needs of patients who underwent surgery for thyroid cancer. Ninety-nine patients in the control group received usual care, and 95 in the navigation group were managed with a navigation program during the perioperative period. The effectiveness of the navigation program was assessed by administering a questionnaire to both groups. Overall satisfaction scores were significantly higher in the navigation than in the control group (p = .025), as were satisfaction scores on the continuity of information (p < .001), the continuity of management (p = .002), the continuity of relationships with healthcare providers (p<.001), and patient empowerment (p < .001). The newly developed navigation program for patients with thyroid cancer was effective in raising satisfaction levels and in actively managing the disease during the perioperative period.

Inactivation of KLF4 promotes T-cell acute lymphoblastic leukemia and activates the MAP2K7 pathway.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a high incidence of relapse in pediatric ALL. Although most T-ALL patients exhibit activating mutations in NOTCH1, the cooperating genetic events required to accelerate the onset of leukemia and worsen disease progression are largely unknown. Here, we show that the gene encoding the transcription factor KLF4 is inactivated by DNA methylation in children with T-ALL. In mice, loss of KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S transition in leukemic cells and promoting the expansion of leukemia-initiating cells. Mechanistically, KLF4 represses the gene encoding the kinase MAP2K7. Our results showed that in murine and pediatric T-ALL, loss of KLF4 leads to aberrant activation of MAP2K7 and of the downstream effectors JNK and ATF2. As a proof-of-concept for the development of a targeted therapy, administration of JNK inhibitors reduced the expansion of leukemia cells in cell-based and patient-derived xenograft models. Collectively, these data uncover a novel function for KLF4 in regulating the MAP2K7 pathway in T-ALL cells, which can be targeted to eradicate leukemia-initiating cells in T-ALL patients.

Cardiac Tamponade due to Suprahepatic Surgical Exploration in Liver Retransplantation: A Case Report.

BACKGROUND: Cardiac tamponade is an emergency condition that requires early recognition and prompt pericardial decompression. Little has been reported on cardiac tamponade in liver retransplantation (reLT), but most cases are fatal. We managed a case of reLT complicated by accidental cardiac tamponade. CASE REPORT: A 59-year-old man underwent an emergency reLT because of liver cirrhosis with recurrent hepatitis B. During the dissection, suprahepatic exploration was attempted, but this resulted in severe hemorrhage because of the many tissue adhesions. After 1 hour of allograft reperfusion, the cardiac index and blood pressure dropped markedly despite volume resuscitation, and the central venous pressure increased abruptly. Using transthoracic echocardiography, cardiac tamponade was diagnosed, and an urgent pericardiotomy was performed. Although bizarre changes in the electrocardiogram were observed briefly, the vital signs normalized. After a short period of hypotension and hyperlactatemia in the intensive care unit, the patient was transferred to a ward in satisfactory condition on postoperative day 7. CONCLUSION: This case demonstrates the need for careful monitoring of hemodynamics during suprahepatic exploration with marked tissue adhesions in reLT.

In vitro Solubility of Copper(II) Sulfate and Dicopper Chloride Trihydroxide for Pigs.

This study was conducted to determine the solubility of copper (Cu) in two sources of copper(II) sulfate (CuSO4) including monohydrate and pentahydrate and three sources of dicopper chloride trihydroxide (dCCTH) including α-form (dCCTH-α), ß-form (dCCTH-ß), and a mixture of α- and ß-form (dCCTH-αß) at different pH and a 3-step in vitro digestion assay for pigs. In Exp. 1, Cu sources were incubated in water-based buffers at pH 2.0, 3.0, 4.8, and 6.8 for 4 h using a shaking incubator at 39°C. The CuSO4 sources were completely dissolved within 15 min except at pH 6.8. The solubility of Cu in dCCTH-α was greater (p<0.05) than dCCTH-ß but was not different from dCCTH-αß during 3-h incubation at pH 2.0 and during 2-h incubation at pH 3.0. At pH 4.8, there were no significant differences in solubility of Cu in dCCTH sources. Copper in dCCTH sources were non-soluble at pH 6.8. In Exp. 2, the solubility of Cu was determined during the 3-step in vitro digestion assay for pigs. All sources of Cu were completely dissolved in step 1 which simulated digestion in the stomach. In Exp. 3, the solubility of Cu in experimental diets including a control diet and diets containing 250 mg/kg of additional Cu from five Cu sources was determined during the in vitro digestion assay. The solubility of Cu in diets containing additional Cu sources were greater (p<0.05) than the control diet in step 1. In conclusion, the solubility of Cu was influenced by pH of digesta but was not different among sources based on the in vitro digestion assay.

Therapeutic targeting of tetraspanin8 in epithelial ovarian cancer invasion and metastasis.

Epithelial ovarian cancer (EOC) invasion and metastasis are complex phenomena that result from the coordinated action of many metastatic regulators and must be overcome to improve clinical outcomes for patients with these cancers. The identification of novel therapeutic targets is critical because of the limited success of current treatment regimens, particularly in advanced-stage ovarian cancers. In this study, we found that tetraspanin 8 (TSPAN8) is overexpressed in about 52% (14/27) of EOC tissues and correlates with poor survival. Using small interfering RNA-mediated TSPAN8 knockdown and a competition assay with purified TSPAN8 large extracellular loop (TSPAN8-LEL) protein, we identified TSPAN8-LEL as a key regulator of EOC cell invasion. Furthermore, monotherapy with TSPAN8-blocking antibody we developed shows that antibody-based modulation of TSPAN8-LEL can significantly reduce the incidence of EOC metastasis without severe toxicity in vivo. Finally, we demonstrated that the TSPAN8-blocking antibody promotes the internalization and concomitant downregulation of cell surface TSPAN8. Collectively, our data suggest TSPAN8 as a potential novel therapeutic target in EOCs and antibody targeting of TSPAN8 as an effective strategy for inhibiting invasion and metastasis of TSPAN8-expressing EOCs.

Comparison of Intraoperative Changes in Blood Glucose According to Model for End-stage Liver Disease Score During Living Donor Liver Transplantation.

BACKGROUND: Recipients of liver transplantation (LT) may experience disturbance of blood glucose balance, which is aggravated by various exogenous factors. The Model for End-stage Liver Disease (MELD) score is an indicator of the severity of pretransplantation liver disease. In this study, we investigated the role of the MELD score in intraoperative changes in blood glucose in patients undergoing living donor LT (LDLT). METHODS: Perioperative data from 280 patients undergoing LDLT were reviewed, including glucose-related data. Intraoperatively, blood glucose levels were checked every hour, and the mean values at each phase of LDLT were calculated. Patients were divided into high and low MELD groups. An unpaired t-test and repeated measures analysis of variance (RMANOVA) were used in intergroup and intragroup comparisons of perioperative blood glucose. RESULTS: The high MELD group consisted of 79 patients. Both the time sequential change during LDLT and the interaction between perioperative blood glucose and MELD score were significant (RMANOVA with multivariate adjustment; P < .05). Pretransplant blood glucose levels did not differ between the 2 groups, but the mean levels of blood glucose were lower and the incidence of hypoglycemia was higher in the high compared with the low MELD group during all phases of LDLT (P < .05). CONCLUSIONS: Blood glucose levels progressively increased during LDLT with an interaction with the MELD score. Patients with a high MELD score had low blood glucose levels and a greater incidence of intraoperative hypoglycemia. MELD score is a useful determinant of intraoperative blood glucose levels in LDLT patients.

Protective effect of eupatilin against renal ischemia-reperfusion injury in mice.

BACKGROUND: Eupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and anti-inflammatory activities. Ischemia-reperfusion injury (IRI) is a major complication after renal transplantation, with inflammatory responses to IRI exacerbating the resultant renal injury. In the present study, we investigated whether eupatilin exhibits renoprotective activities against ischemia-reperfusion-induced acute kidney injury in mice. MATERIALS AND METHODS: Renal IRI was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion for 48 hours. Eupatilin (10 mg/kg body weight p.o.) was administered 4 days before IRI. RESULTS: Treatment with eupatilin significantly decreased neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels in urine, blood urea nitrogen level, and serum creatinine levels, as well as kidney tubular injury. Western blotting indicated that eupatilin significantly increased the levels of heat shock protein 70 and B-cell lymphoma protein, and it attenuated inducible nitric oxide synthase, Bcl-2-associated X protein, and caspase-3 levels 48 hours after IRI. CONCLUSION: Our findings suggest that eupatilin is a promising therapeutic agent against acute ischemia-induced renal damage.