Co-development of autoimmune hepatitis and Sj?gren's syndrome triggered by the administration of herbal medicines

Autoimmune hepatitis (AIH) has been reported in association with Sjögren''s syndrome (SS). Drug-induced AIH has been rarely reported. A rare case of the co-development of AIH and SS in a 53-year-old woman after the consumption of herbal medicines is described. After admission, the patient complained of dryness in her mouth, and she was subsequently diagnosed with SS, which had not been detected previously. The patient''s bilirubin and aminotransferase levels initially decreased following conservative management; however, they later began to progressively increase. A diagnosis of AIH was made based on the scoring system proposed by the International Autoimmune Hepatitis Group. The patient was administered a combination of prednisolone and azathioprine, and the results of follow-up liver-function tests were found to be within the normal range. This is an unusual case of AIH and SS triggered simultaneously by the administration of herbal medicines.     

Finite Element Modeling of Stress Distribution in Intervertebral Spacers of Different Surface Geometries

Intervertebral disc spacers using bioactive ceramics have been used to treat degenerative spinal disease. Tooth‐shaped spacers are commonly used to prevent migration, but there is a possibility of fracture when inserted or after insertion. Intervertebral disc spacers with either an isosceles triangle‐shaped tooth (T1) or a right triangle‐shaped tooth (T2) were used as a control group. The design factors for the experimental group were modified to prevent fractures induced by stress concentration, and the surfaces of the spacers were designed as either an isosceles triangle‐shaped valley (V1) or a right triangle‐shaped valley (V2). Linear analysis using finite element model (FEM) was performed, and Von Mises stress distribution was calculated by applying 1000 N of uniformly distributed load. Samples of the V2 design were made with bioactive glass‐ceramics (BGS‐7) and evaluated for compressive strength, fatigue degree, and impact strength. Von Mises stress was highest at the first tooth from the posterior side for the control group and at the center for the experimental group. Compared with the control group, the experimental group showed 18.4% and 82.5% reduction (V1 vs. T1 and V2 vs. T2, respectively) in the maximum stress at the bottom of the valleys. The FEM analysis revealed that the V2 design had the most even load distribution. The V2 samples with bioactive glass‐ceramics were evaluated for compressive strength, and all six samples were not fractured up to 24 000 N. However, the average impact strength was 19.42 kN, suggesting that momentary force caused damage at a lower load than compression with a steady speed. The BGS‐7 intervertebral disc spacer with V2 design was not fractured during the fatigue test at maximum pressure of 8000 N, R ≥10, 5 Hz, and 5 million cycles. These data confirm that the BGS‐7 spacer with the V2 design may be clinically applicable. Collectively, the modified surface geometry of the experimental group significantly lowered Von Mises stress values at the bottom of the valleys, and thus the possibility of fracture by compressive load was greatly reduced. Also, impact during insertion was confirmed to cause fracture more easily, as the impact strength was lower than the compressive strength in the experimental group.     

Decreased endothelial progenitor cells and increased serum glycated albumin are independently correlated with plaque-forming carotid artery atherosclerosis in type 2 diabetes patients without documented ischemic disease

Background:?The aim of the present study was to investigate the serum levels of endothelial progenitor cells (EPCs) in type 2 diabetic patients without documented ischemic disease and the association between EPCs and atherosclerotic plaque formation in the carotid artery. Methods and Results:?A clinic-based, prospective study of type 2 diabetic patients was conducted. A total of 73 subjects were enrolled in this study after cardiac magnetic resonance imaging and ankle-brachial index measurements to exclude patients with ischemic disease. Plaque formation in the carotid artery was measured on ultrasonography. Circulating EPCs (CD34(+)/CD133(+)/CD309(+) cells) were counted on flow cytometry. Compared to subjects without carotid artery plaques, patients with plaques were significantly older (P=0.006) and had decreased EPC count (P=0.027). Serum glycated albumin (GA) level and the GA/glycated hemoglobin ratio tended to decrease in patients with plaques (P=0.091 and 0.067, respectively). Other cardiovascular disease risk factors were not significantly different between the 2 groups. On binary logistic regression analysis old age, low EPC count, and high serum GA level were independently correlated with carotid artery plaque formation. Conclusions:?EPC count and serum GA level appear to be a protective and an aggravating factor for endothelial damage, respectively, and therefore, a reduced EPC count or an increased GA level results in atherosclerotic plaque formation in type 2 diabetic patients. (Circ J?2012; 76: 2273-2279).     

Reliability testing of tendon disease using two different scanning methods in patients with rheumatoid arthritis

Objective. To assess the intra- and interobserver reliability of musculoskeletal ultrasonography (US) in detecting inflammatory and destructive tendon abnormalities in patients with RA using two different scanning methods. Methods. Thirteen observers examined nine patients with RA and one healthy individual in two rounds independently and blindly of each other. Each round consisted of two consecutive examinations, an anatomy-based examination and a free examination according to personal preferences. The following tendons were evaluated: wrist extensor compartments 2, 4 and 6, finger flexor tendons 3 and 4 at MCP level, tibialis posterior tendon and both peronei tendons. Overall, positive and negative agreements and κ-values for greyscale (GS) tenosynovitis, peritendinous power Doppler (PPD) signal, intratendinous power Doppler (IPD) signal and GS tendon damage were calculated. Results. Intraobserver κ-value ranges were 0.53-0.55 (P?相似文献   

A case of intrahepatic cholangiocarcinoma associated with Type IV choledochal cyst

Anomalous union of the pancreaticobiliary duct (AUPBD) is a congenital anomaly that is defined as a junction of the bile duct and pancreatic duct outside the duodenal wall. This anomaly results in a loss of normal sphincteric mechanisms at the pancreaticobiliary junction. As a result, regurgitation of pancreatic juice into the biliary system develops and causes choledochal cysts, choledocholithiasis, cholangitis, pancreatitis and malignancy of the biliary tract. Gallbladder cancer or common bile duct cancer associated with AUPBD and choledochal cysts have been frequently reported. But, intrahepatic cholangiocarcinoma associated with this condition has been only rarely reported. Here, we report a case of intrahepatic cholangiocarcinoma associated with AUPBD and choledochal cyst.     

Symptomatic improvement of diffuse esophageal spasm after botulinum toxin injection

Diffuse esophageal spasm, an uncommon esophageal motility disorder, has recently been defined using high-resolution manometry. Patients with distal esophageal spasm usually complain of chest pain or dysphagia. The etiology and pathophysiology of this disorder are poorly known, and treatment options are limited. However, some options to improve symptoms are available, including endoscopic injection of botulinum toxin. Nevertheless, few reports have described the effects of endoscopic injection of botulinum toxin in patients with symptomatic diffuse esophageal spasm with clear endoscopic and high-resolution manometry images. Here, we report a case of diffuse esophageal spasm diagnosed with high-resolution manometry and treated by endoscopic injection of botulinum toxin with good results at the 7-month follow-up.     

Reverse shape selectivity of hexane isomer in ligand inserted MOF-74

Separation of linear, mono-branched, and di-branched isomers is critically important in the petrochemical industry. In this computational study, we demonstrate that the ligand inserted Mg-MOF-74 structure leads to a reverse selectivity effect (i.e. phenomenon that preferentially allows larger species molecules to permeate in a gas mixture) of hexane isomers in the resulting material. Molecular dynamics simulations suggest that strong confinement of the di-branched hydrocarbons in the small pores lead to reverse selectivity. Over a magnitude difference in diffusivity between linear alkanes and their di-branched isomers was observed, clearly showing the steric effects imposed by the pore structure.

The ligand inserted Mg-MOF-74 structure leads to a reverse selectivity effect (i.e. phenomenon that preferentially allows larger species molecules to permeate in a gas mixture) of hexane isomers in the resulting material.

In the petrochemical industry, separation of the hexane isomers is an important process that removes impurities for fuel purification and the isolation of mixtures for applied further reaction.^1,2 The sieving of n-hexane and its branched isomers is particularly interesting research because of the varying octane numbers in the isomers affecting the gasoline production,^3–5 and as such, it is imperative to facilitate separation of these isomers. Unfortunately, this separation is particularly challenging due to the similar polarizabilities and chemical inertness of the molecules, leading one to resort to highly energy expensive distillation processes.^1,6The presently used methods such as molecular sieving using zeolites and the conventional distillation processes still include mixtures of the isomers that lowers the overall octane number^7,8 compared to the pure di-branched molecule composition. To discover the adsorbent materials that can completely separate the isomers into their individual components, many researchers have investigated adsorbent materials with an appropriate pore size and shape.^9–12 Recently, metal–organic frameworks (MOFs) have attracted great deal of attention from the researchers due to their potential applications in gas separations,^13–20 CO₂ capture,^21,22 catalysis,^23–26 water harvesting^27–29 and several other applications.^30–32 MOFs are crystalline microporous materials composed of inorganic metal nodes and organic linkers^33–35 and via combining various metal clusters and organic linkers, MOFs can be tuned specifically to ideal shapes and pore chemical environment for targeted gas separations.^36–38 This tunability allows one to potentially design MOFs that are ideal for hexane isomers. Bárcia et al.³⁹ firstly used MOFs called Zn(BDC)(DABCO)_0.5 (MOF-1) to separate hexane isomers, although this MOF showed low adsorption capacities. Also, Herm et al.¹² synthesized a MOF named Fe₂(BDP)₃ (BDP²⁻ = 1,4-benzenedipyrazolate), which contain triangular pore channels that can discriminate hexane isomers better than the commercial standard. More recently, Lv et al.⁴⁰ demonstrated that [Fe₃(μ3-O)(COO)₆] and 2,2-bis(4-carboxyphenyl)-hexafluoropropane (6FDCA) have strong capability to separate n-hexane from its branched isomers on the basis of a kinetically controlled molecular sieve separation.Overall, conventional wisdom dictates that one would seek to design materials whose pore limiting diameter can separate the molecules of interest within the mixture. With that being said, there have been few observances where the ordering based on kinetic diameters is reversed (in what is called reverse selectivity).⁴¹ Previous study by Bárcia et al.⁴² used the concept of “length entropy” to describe the adsorption and separation behavior in UiO-66(Zr). They showed that UiO-66(Zr) preferentially adsorb branched alkanes over their linear isomer, in what they called “reverse selectivity”. Moreover, Pan et al.⁴³ described the unusual reverse selective separation of n-butane from normal hydrocarbons above C₄ in a fluorinated MOF with 1D channels. Additionally, reverse selectivity has also been mentioned in recent works with IRMOF-8 (ref. 44) and UiO-66@SiO₂ (ref. 45) with regards to linear and iso-alkane separation.In our previous computational work, we designed the ligand inserted MOF frameworks using the ligand insertion strategy. Using computational analysis, these structures showed increase in the working capacity of CO₂ under humid flue gas conditions,²² utility as a catalyst for enhanced ethane oxidation²⁵ and potential usage in water harvesting material.²⁹ In the current work, the dpt ligand inserted Mg-MOF-74 structures with 1-D channel was used to examine the reverse selectivity of hexane isomer and separation properties by considering mixtures of n-hexane and its branched isomers (2,2-dimethylbutane, 2,3-dimethylbutane, 2-methylpentane and 3-methylpentane). In the context of the hexane isomer separation, the inserted ligand finely tuned the shape and the size of the pores within the MOF such that branched isomer can reverse selectively pass through the MOF channel.Optimization of the MOFs and the hexane isomer binding energy calculations were conducted using the first-principles calculations through the density functional theory (DFT) as implemented by the plane-wave pseudopotential approach in Quantum Espresso.⁴⁶ The second version of a van der Waals dispersion-corrected density functional (vdW-DF2)⁴⁷ was used to describe the dispersion interactions. Ultrasoft pseudopotentials were used for GGA and vdW-DF2 calculations. A 2 × 2 × 2 k-point mesh was used for the Brillouin zone sampling in the reciprocal space. The kinetic energy and charge density planewave cutoff were set to 30 Ry and 240 Ry, respectively.All molecular dynamics simulations were carried out using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) program.⁴⁸ In the simulations, the MOF structures are set to be fixed with the dpt ligand and the hexane isomers considered to be flexible, incorporating all intramolecular motions such as bond vibrations, bond angle bending, and torsional motions. All non-bonded interactions between the atoms were calculated using the Lennard-Jones (LJ) potential. Adsorbate–adsorbate and adsorbate–MOF interactions were truncated at 14 Å and at 12.8 Å with analytical tail-corrections applied for interactions beyond this cutoff distance, respectively. The LJ parameters for the atoms of the MOF were taken from the UFF⁴⁹ and The TraPPE force field were employed to model the inter- and intramolecular interactions of the hexane isomers as previous studies reported that these models accurately model the adsorption and diffusion properties of alkanes⁵⁰ and nHEX⁵¹ in the MOFs. Initially, all systems were equilibrated for 2 ns in an NVT ensemble, and afterwards, another 10 ns of simulation was performed in the NVT ensemble during which the equilibrated phase space trajectories were stored at every 10 ps. These trajectories were then used to analyze the diffusion behavior of the hexane isomers with the diffusion coefficients calculated from the mean square displacements (MSD) of the molecules using the Einstein''s relation.The ligand insertion strategy within the MOF-74 structure can be used to reconfigure the pore space to enhance the separation performance. To demonstrate this, a size-matching regulated ligand (2,4-di(4-pyridinyl)-1,3,5-triazine (dpt)) was inserted as shown in Fig. 1(a).Open in a separate windowFig. 1Illustration of pore space partitioned Mg-MOF-74 using ligands 2,4-di(4-pyridinyl)-1,3,5-triazine. (a) Viewed along z axis and (b) side view of the channels showing the cylindrical channel.The insertion of 2,4-di(4-pyridinyl)-1,3,5-triazine (dpt) ligands into the hexagonal channels of Mg-MOF-74 was demonstrated in our previous theoretical study on catalyst for ethane oxidation.²⁵ In the previous work, the computed DFT binding energy of the dpt ligand was −198.3 kJ mol⁻¹ in the Mg-MOF-74 structures, providing evidence that the ligands would stay intact and not wash away, post synthesis. The dpt ligands were inserted such that the distance between the two dpt ligands is 8.3 Å along the channel direction in the z-axis (Fig. 1(b)). In the alkane separations, configurational and length entropy effects may act in a completely different manner. These effects plays a bigger role for separating linear and branched alkanes in materials such as AFI⁵² and MOF-74 that have cylindrical channels. Hence, it is important to consider both the maximum diameter (i.e. molecular length)⁵³ of the molecules as well as kinetic diameter. As can be seen from 53,54

Alteration of the E-cadherin/β-Catenin Complex Predicts Poor Response to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment

Background

Epidermal growth factor receptor (EGFR) mutation alone may be insufficient to predict clinical outcomes in the response to EGFR-tyrosine kinase inhibitor (TKI) therapy. The secondary mutation T790 M and MET amplification are mechanisms of acquired resistance to EGFR-TKI in approximately 50 % of patients, but the remaining mechanisms are unknown.

Methods

Eight metastatic lesions and specimens from 41 non-small cell lung carcinoma (NSCLC) patients harbouring activating EGFR mutations who underwent surgical resection and EGFR-TKI therapy were available. Immunohistochemistry was used to evaluate E-cadherin, β-catenin, and PTEN. Chromogenic in situ hybridisation and silver-enhanced in situ hybridisation were used to evaluate EGFR and MET amplification.

Results

Patients with E-cadherin/β-catenin alteration showed a poor objective response rate (ORR) (p = 0.005) and shorter overall survival (p = 0.059). Additionally, β-catenin alteration was associated with a poor ORR (p = 0.012). Of the metastatic tumours, three cases (37.5 %) showed the acquisition of altered E-cadherin/β-catenin and PTEN loss and two cases (25 %) demonstrated MET/EGFR amplification.

Conclusions

Altered E-cadherin/β-catenin expression in NSCLC harbouring EGFR mutations was associated with a poor response to EGFR-TKI. During metastatic progression, changes in E-cadherin/β-catenin were found. These results may suggest that E-cadherin/β-catenin alteration is related to poor TKI response and resistance.