One of the most important topics in spintronics is spin transport. In this work, spin transport properties of two-dimensional electron gas in AlxGa1-xN/GaN heterostructure were studied by helicity-dependent photocurrent measurements at room temperature. Spin-related photocurrent was detected under normal incidence of a circularly polarized laser with a Gaussian distribution. On one hand, spin polarized electrons excited by the laser generate a diffusive spin polarization current, which leads to a vortex charge current as a result of anomalous circular photogalvanic effect. On the other hand, photo-induced spin polarized electrons driven by a longitudinal electric field give rise to a transverse current via anomalous Hall Effect. Both of these effects originated from the Rashba spin-orbit coupling. By analyzing spin-related photocurrent varied with laser position, the contributions of the two effects were differentiated and the ratio of the spin diffusion coefficient to photo-induced anomalous spin Hall mobility Ds/μs = 0.08 V was extracted at room temperature.
Ribose-phosphate pyrophosphokinase 1 (PRPS1) was identified and isolated as a differentially expressed gene between deltamethrin-susceptible (DS) and deltamethrin-resistant (DR) Culex pipiens pallens and Aedes albopictus C6/36 cell line through microarray and 2D-Gel. An open reading frame of PRPS1 cloned from C. pipiens pallens has 1,011 bp and encodes for a 336 amino acids protein which shares high homology with Culex quinquefasciatus. Real-time polymerase chain reaction was used to determine the transcript expression level of PRPS1 in DS and DR strains. The expression levels of PRPS1 were higher in DR laboratory strains and natural population JXZ-DR, JXZ-LDR. PRPS1 was also detected and expressed at all developmental stages of C. pipiens pallens and increased expression level in DR3 strain than DS strain in the third and fourth instar larvae, female and male stages. In addition, to further investigate the role of PRPS1 in deltamethrin resistance, PRPS1 was transiently expressed in A. albopictus C6/36 cells and detected by western blotting. Cells transfected with PRPS1 had an increased resistance to deltamethrin compared with control cells. These results suggested that the increased expression level of PRPS1 may play roles in the regulation of deltamethrin resistance.
Anopheles sinensis is an important mosquito vector of Plasmodium vivax, which is the most frequent and widely distributed cause of recurring malaria throughout Asia, and particularly in China, Korea, and Japan.
We performed 454 next-generation sequencing and obtained a draft sequence of A. sinensis assembled into scaffolds spanning 220.8 million base pairs. Analysis of this genome sequence, we observed expansion and contraction of several immune-related gene families in anopheline relative to culicine mosquito species. These differences suggest that species-specific immune responses to Plasmodium invasion underpin the biological differences in susceptibility to Plasmodium infection that characterize these two mosquito subfamilies.
The A. sinensis genome produced in this study, provides an important resource for analyzing the genetic basis of susceptibility and resistance of mosquitoes to Plasmodium parasites research which will ultimately facilitate the design of urgently needed interventions against this debilitating mosquito-borne disease.
Genome; Anopheles sinensis; Malaria
Objective: Acute myocardial infarction (AMI) is a most serious cardiovascular disease with high morbidity and mortality. Novel biomarkers for AMI are explored continuous. MicroRNAs (miRNAs, miRs) are present in the circulation in a consistent, stable, and reproducible manner, attracting major interest of using circulating miRNAs as biomarkers. In plasma, miR-208a and miR-499 are considered to be the best candidate for AMI diagnosis. However, serum has slightly higher miRNA yields compared to plasma and the majority of archived samples are stored in form of serum, marking interesting to determine whether miR-208a and miR-499 in serum can be used as biomarkers for AMI. Methods: AMI was induced by coronary ligation and the serum and heart tissues were collected. The levels of miR-208a and miR-499 in serum and heart tissues were determined using TaqMan-based miRNA quantitative real-time polymerase chain reactions (qRT-PCRs). Results: Serum miR-208a was increased by 36-fold and 51-fold while miR-499 was elevated by 103-fold and 95-fold at 4 h and 24 h after AMI. Moreover, the expression level of miR-499 was significantly decreased in the myocardial infarct zone comparing to the remote zone or the sham group while miR-208a remained unchanged. Conclusion: Serum miR-499 and miR-208a might be potential biomarkers for AMI. miR-499 might be released from damaged heart to the circulation.
Serum; microRNA; acute myocardial infarction; biomarker
AIM: To explore risk factors of lymphatic metastasis (LM) in gallbladder cancer, and their potential to complement unsatisfactory radiological detection.
METHODS: Radiological detection of LM by computed tomography (CT) was reported to fail in more than 60% of patients with pathological LM. In order to find risk factors highly suggestive of LM other than radiological manifestations, the documents of 63 patients were analyzed statistically. Except for 4 patients having T1a disease, in whom cholecystectomy is enough for radical resection, 59 patients underwent lymphadenectomy with at least 3 lymph nodes dissected. Fifty point eight percent (32/63) of patients were found to have LM during pathological examination. The median number of dissected lymph nodes was 6 (range 3-20).
RESULTS: Only 31.3% (10/32) of patients with LM were detected by CT. Through multivariate analysis, two risk factors of LM were discovered as age < 60 years (OR = 6.24; P < 0.01) and carbohydrate antigen (CA) 19-9 elevation (OR = 5.70; P < 0.05). By analysis of patients with pathological LM but failed to be detected by CT, 81.8% (18/22) of patients had at least one risk factor, including 31.3% (10/32) who had the risk factor of age < 60 years, and 37.5% (12/32) who had the risk factor of CA 19-9 elevation. Besides, among patients with LM (n = 32), those whose age were younger than 60 years (OR = 3.41; P < 0.05) were more likely to have 3 or more positive lymph nodes.
CONCLUSION: Age < 60 years and CA 19-9 elevation could complement radiological detection of LM. Patients aged < 60 years are at higher risk of multiple positive nodes.
Gallbladder cancer; Multidetector computed tomography; Lymphatic metastasis; Lymph node excision; Carbohydrate antigen 19-9; Age
Norcantharidin (NCTD), a demethylated analog of cantharidin derived from blister beetles, has attracted considerable attentions in recent years due to their definitely toxic properties and the noteworthy advantages in stimulating bone marrow and increasing the peripheral leukocytes. Hence, it is worth studying the anti-tumor effect of NCTD on human prostate cancer cells DU145. It was found that after the treatment of NCTD with different concentrations (25-100 μM), the cell proliferation was significantly inhibited, which led to the appearance of micronucleus (MN). Moreover, the cells could be killed in a dose-/ time-dependent manner along with the reduction of PCNA (proliferating cell nuclear antigen) expression, destruction of mitochondrial membrane potential (MMP), down-regulation of MnSOD, induction of ROS, depletion of ATP, and activation of AMPK (Adenosine 5‘-monophosphate -activated protein kinase) . In addition, a remarkable release of cytochrome c was found in the cells exposed to 100 μM NCTD and exogenous SOD-PEG could eliminate the generation of NCTD-induced MN. In conclusion, our studies indicated that NCTD could induce the collapse of MMP and mitochondria dysfunction. Accumulation of intercellular ROS could eventually switch on the apoptotic pathway by causing DNA damage and depleting ATP.
Objective: Cardiac hypertrophy is a compensatory response of the heart to maintain its pumping capacity. Cardiac hypertrophy can be divided into pathological hypertrophy and physiological hypertrophy. The major forms of physiological hypertrophy include developing in response to developmental maturation, exercise, and pregnancy, which is adaptive and beneficial. Exercise has well-known beneficial cardiovascular effects and has recently been shown to be protective for myocardial ischemia-reperfusion injury. However, there are conflicting reports for the cardiac protective effects of pregnancy-induced hypertrophy. In the present study, we investigated the effects of pregnancy-induced physiological hypertrophy in cardiac ischemia-reperfusion injury and if cardiac progenitor cells were activated during pregnancy. Methods: Physiological hypertrophy was induced in pregnancy and the mRNA levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined by real-time polymerase chain reactions (RT-PCRs) analysis. Triphenyltetrazolium chloride staining was used to determine the cardiac ischemia-reperfusion injury. c-Kit and Nkx2.5 levels were determined by RT-PCRs, western blot and immunofluorescent staining. Results: Heart weight (HW) and the ratio of HW to tibia length were increased while mRNA levels of ANP and BNP remained unchanged. Pregnancy-induced physiological hypertrophy protected against cardiac ischemia-reperfusion injury. In pregnancy, c-Kit positive cardiac progenitor cells were activated. Conclusion: This study presents that pregnancy-induced physiological hypertrophy activates cardiac progenitor cells and thereafter protects against cardiac ischemia-reperfusion injury.
Pregnancy; hypertrophy; physiological; ischemia/reperfusion; cardiac progenitor cells
Babesiosis is an emerging health risk in several parts of the world. However, little is known about the prevalence of Babesia in malaria-endemic countries. The area along the China-Myanmar border in Yunnan is a main endemic area of malaria in P.R. China, however, human infection with Babesia microti (B. microti) is not recognized in this region, and its profile of co-infection is not yet clear.
To understand its profile of co-infections with B. microti, our investigation was undertaken in the malaria-endemic area along the China-Myanmar border in Yunnan between April 2012 and June 2013. Four parasite species, including B. microti, Plasmodium falciparum (P. falciparum), P. vivax, and P. malariae, were identified among 449 suspected febrile persons detected by nested polymerase chain reaction (PCR) assay based on small subunit ribosomal ribonucleic acid (RNA) genes of B. microti and Plasmodium spp.
Of all the collected samples from febrile patients, mono-infection with B. microti, P. vivax, P. falciparum, and P. malariae accounted for 1.8% (8/449), 9.8% (44/449), 2.9% (13/449), and 0.2% (1/449), respectively. The rate of mixed infections of B. microti with P. falciparum or P. vivax are both 0.2% (1/449), and mixed infections of P. falciparum and P. vivax accounted for 1.1% (5/449).
This report supports the hypothesis that babesiosis caused by B. microti is emerging along the China-Myanmar border in the Yunnan province, P.R. China, but it was ignored because of low parasitemia or mixed infection with Plasmodium spp. More sensitive and specific diagnosis methods are needed to find the rapid response mechanism of emergency for babesiosis and malaria co-prevalence areas.
Babesia; Plasmodium; Co-infection; China-Myanmar border
The integrin family of cell adhesion receptors mediates bi-directional signaling: “inside-out” signaling activates the ligand binding function of integrins and “outside-in” signaling mediates cellular responses induced by ligand binding to integrins leading to cell spreading, retraction, migration, and proliferation. Integrin signaling requires both heterotrimeric G proteins and monomeric small G proteins. This review focuses on recent development in the roles of G proteins in integrin outside-in signaling. The finding of direct interaction between the heterotrimeric G protein subunit Gα13 and integrin β subunits reveals a new mechanism for integrin signaling, and also uncovers a crosstalk between the signaling pathways initiated by G protein-coupled receptors (GPCRs) and integrins. This crosstalk, which may be referred to as “inside-outside-in” signaling, dynamically regulates contractility and greatly promotes integrin outside-in signaling
α-Oxy amides are prepared through enantioselective synthesis using a sequence beginning with a Henry addition of bromonitromethane to aldehydes, and finishing with Umpolung Amide Synthesis (UmAS). Key to high enantioselection is the finding that ortho-iodo benzoic acid salts of the chiral copper(II) bis(oxazoline) catalyst deliver both diastereomers of the Henry adduct with high enantiomeric excess, homochiral at the oxygen-bearing carbon. Overall, this approach to α-oxy amides provides an innovative complement to alternatives that focus almost entirely on the enantioselective synthesis of α-oxy carboxylic acids.
Mixed epithelial and stromal tumor of the kidney (MESTK) is the term given to a class of uncommon biphasic tumors of the kidney, with few reported cases. We describe eight cases of MESTK with detailed clinicopathological data and follow-up information. With this report, we hope to increase clinical awareness that MESTK should be considered as one of the possible diagnoses for cystic renal mass, especially in peri-menopausal women or those who receive hormone therapy. In addition, regular follow-up is necessary for the any cases with malignant potential.
Kidney; Mixed epithelial and stromal tumor
In non-climacteric fruits, the respiratory increase is absent and no phytohormone is appearing to be critical for their ripening process. They must remain on the parent plant to enable full ripening and be picked at or near the fully ripe stage to obtain the best eating quality. However, huge losses often occur for their quick post-harvest senescence. To understanding the complex mechanism of non-climacteric fruits post-harvest senescence, we constructed two small RNA libraries and one degradome from strawberry fruit stored at 20°C for 0 and 24 h. A total of 88 known and 1224 new candidatemiRNAs, and 103 targets cleaved by 19 known miRNAs families and 55 new candidatemiRNAs were obtained. These targets were associated with development, metabolism, defense response, signaling transduction and transcriptional regulation. Among them, 14 targets, including NAC transcription factor, Auxin response factors (ARF) and Myb transcription factors, cleaved by 6 known miRNA families and 6 predicted candidates, were found to be involved in regulating fruit senescence. The present study provided valuable information for understanding the quick senescence of strawberry fruit, and offered a foundation for studying the miRNA-mediated senescence of non-climacteric fruits.
The prophenoloxidase subunit A3 (proPOA3) gene was cloned from Culex pipiens pallens, which had an open reading frame of 2,061 bp encoding a putative 686 amino acid protein. The deduced amino acid sequence shares 98% with proPOA3 from Cx. quinquefasciatus. ProPOA3 is expressed at all developmental stages of Cx. pipiens pallens. Significant negative correlation was observed between proPOA3 expression and deltamethrin resistance in resistant Cx. pipiens pallens. Furthermore, proPOA3 expression levels were significantly lower in deltamethrin-resistant mosquitoes than in susceptible mosquitoes collected at four locations in Eastern China. However, we did not find any substantial change in proPOA3 expression in field-collected resistant Anopheles mosquitoes. Moreover, overexpressing proPOA3 in C6/36 cells led to more sensitivity to deltamethrin treatment. In laboratory and field-collected resistant Cx. pipiens pallens, a valine to isoleucine mutation (769G>A) and two synonymous mutations (1116G>C and 1116G>A) were identified in proPOA3. In addition, the mutation frequency of 769G>A and 1116G>C increased gradually, which corresponded with raised deltamethrin resistance levels. Taken together, our study provides the first evidence that proPOA3 may play a role in the regulation of deltamethrin-resistance in Cx. pipiens pallens.
Culex pipiens pallens; deltamethrin resistance; prophenoloxidase; mutation
Deltamethrin (DM) insecticides are currently being promoted worldwide for mosquito control, because of the high efficacy, low mammalian toxicity and less environmental impact. Widespread and improper use of insecticides induced resistance, which has become a major obstacle for the insect-borne disease management. Resistance development is a complex and dynamic process involving many genes. To better understand the possible molecular mechanisms involved in DM resistance, a proteomic approach was employed for screening of differentially expressed proteins in DM-susceptible and -resistant mosquito cells. Twenty-seven differentially expressed proteins were identified by two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). Four members of the ubiquitin-proteasome system were significantly elevated in DM-resistant cells, suggesting that the ubiquitin-proteasome pathway may play an important role in DM resistance. Proteasome subunit beta type 6 (PSMB6) is a member of 20S proteasomal subunit family, which forms the proteolytic core of 26S proteasome. We used pharmaceutical inhibitor and molecular approaches to study the contributions of PSMB6 in DM resistance: the proteasome inhibitor MG-132 and bortezomib were used to suppress the proteasomal activity and siRNA was designed to block the function of PSMB6. The results revealed that both MG-132 and bortezomib increased the susceptibility in DM-resistant cells and resistance larvae. Moreover, PSMB6 knockdown decreased cellular viability under DM treatment. Taken together, our study indicated that PSMB6 is associated with DM resistance in mosquitoes and that proteasome inhibitors such as MG-132 or bortezomib are suitable for use as a DM synergist for vector control.
The expression level of CC-chemokine receptor 5 (CCR5) is enhanced post inflammatory stimulations and might play a crucial role on inflammatory cells infiltration post myocardial ischemia. The purpose of this study was to evaluate the role of CCR5 on myocardial ischemia–reperfusion (I/R) injury in rats. Adult male rats were randomized to sham group, I/R group (I/R, 30 min coronary artery occlusion followed by 2-h reperfusion), ischemic preconditioning (I/R + Pre), CCR5 antibody group [I/R + CCR5Ab (0.2 mg/kg)], and CCR5 agonist group [I/R + CCR5Ago, RNATES (0.1 mg/kg)], n = 12 each group. The serum level of creatine kinase (CK) and tumor necrosis factor α (TNF-α) were measured by ELISA. Myocardial infarction size and myeloperoxidase (MPO) activity were determined. Myocardial protein expression of CCR5 and intercellular adhesion molecule-1 (ICAM-1) were evaluated by Western blotting and immunohistochemistry staining, respectively. Myocardial nuclear factor-kappa B (NF-κB) activity was assayed by electrophoretic mobility shift assay. Myocardial CCR5 protein expression was significantly reduced in I/R + Pre group (P < 0.05 vs. I/R) and further reduced in I/R + CCR5Ab group (P < 0.05 vs. I/R + Pre). LVSP and ±dP/dtmax were significantly lower while serum CK and TNF-α as well as myocardial MPO activity, ICAM-1 expression, and NF-κB activity were significantly higher in I/R group than in sham group (all P < 0.05), which were significantly reversed by I/R + Pre (all P < 0.05 vs. I/R) and I/R + CCR5Ab (all P < 0.05 vs. I/R + Pre) while aggravated by I/R + CCR5Ago (all P < 0.05 vs. I/R). Our results suggest that blocking CCR5 attenuates while enhancing CCR5 aggravates myocardial I/R injury through modulating inflammatory responses in rat heart.
Ischemia–reperfusion injury; CC-chemokine receptor 5; Antibody; Agonist; Nuclear factor-kappa B
Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T>A (hereafter T>A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T>A) were in Hardy-Weinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P < 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P < 0.05). Therefore, the heterozygous genotype c.-166T>A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.
Lung cancer; Nicotinic acetylcholine receptors; CHRNA5 gene; Single nucleotide polymorphisms
We report an unusual case of retrovesical ectopic prostate tissue in a 73-year-old man with primary prostate cancer. The man’s prostate-specific antigen was 24.66 ng/ml.Transabdominal ultrasonography, pelvic computed tomography,and pelvic magnetic resonance imaging demonstrated a heterogeneous 8.5 × 8.0 × 7.0 cm mass in contact with the posterior wall of the urinary bladder. The patient underwent a retropubic radical prostatectomy and resection of tumor. Pathological examination of prostate revealed a prostatic adenocarcinoma, Gleason score of 4 + 5 = 9, and the retrovesical tumor was confirmed to be a benign prostate tissue.
Ectopic prostate; Retrovesical space; Prostate cancer
Continuous and excessive application of insecticides has resulted in the rapid development of insecticide resistance in several mosquito species, including Culex pipiens pallens. Previous studies in our laboratory found that arrestin gene expression was higher in the deltamethrin-resistant (DR) strain than in the deltamethrin-susceptible (DS) strain of Cx. pipiens pallens. Similarly, other studies reported that arrestin was highly expressed in permethrin-resistant Cx. quinquefasciatus and in dichlorodiphenyltrichloroethane (DDT)-resistant Drosophila melanogaster.
Full-length cDNAs of an arrestin gene were cloned from Cx. pipiens pallens via polymerase chain reaction (PCR) and rapid amplification of cDNA end (RACE). The mRNA levels of the arrestin gene in the whole life cycle of DR and DS strains of Cx. pipiens pallens were investigated via quantitative real-time PCR. In addition, the relationship between arrestin and deltamethrin (DM) resistance were identified using genetic overexpression strategies and arrestin RNAi in mosquito cells. Cell viability was analyzed with cholecystokinin octapeptide after DM treatment. Moreover, the mRNA levels of cytochrome P450 6A1 (CYP6A1) and opsin in the transfected cells and controls were analyzed.
Complete arrestin gene sequence was cloned and expressed throughout the life cycle of Cx. pipiens pallens. Moreover, arrestin was significantly upregulated in the DR strain, compared with that in the DS strain at the egg, pupae, and adult stages. Arrestin overexpression comparably increased the mosquito cell viability, whereas arrestin knockdown by siRNA decreased mosquito cell viability with deltamethrin (DM) treatment. Meanwhile, the mRNA levels of CYP6A1 and opsin were upregulated in mosquito cells transfected with arrestin and downregulated in mosquito cells with arrestin knockdown.
This study presented the first evidence that arrestin might be associated with insecticide resistance in Cx. pipiens pallens.
Insecticide resistance; Arrestin; Gene cloning; Transfection; SiRNA; Cell viability
The aim of the study was to review the clinical features and treatments of 10 (9 males and 1 female; age range, 61–73 years; median age, 67 years) upper urinary tract inverted papilloma (IP) cases between 1995 and 2010. The clinical syndromes, diagnostic procedures, treatments and results of the follow-up were evaluated. The results showed that the site of tumor development was the ureter in 6 cases and the renal pelvis in 4 cases. It was also identified that 7 tumors developed on the left side and 3 developed on the right side of the ureter and renal pelvis, respectively. A nephroureterectomy was performed in the first 6 cases, while a partial ureterectomy was performed in 3 cases and a local resection was performed endoscopically in 1 case. All but 2 tumors were solitary, ranging from 5 to 30 mm in diameter. Occurrence in association with transitional cell carcinoma was identified in one case. All 10 patients were subject to follow-up (range, 19–120 months; median, 59 months), during which no recurrence was found. Local excision is considered as adequate treatment when upper urinary tract IP is diagnosed according to strictly defined criteria.
upper urinary tract; inverted papilloma; prognosis; excision
Ileal pouch-anal anastomosis (IPAA) following total proctocolectomy has become the surgical treatment of choice for ulcerative colitis patients who have medically refractory disease or neoplasia. Unfortunately, various metabolic complications have been reported with this surgical procedure, including anemia, vitamin B12 deficiency, bile salt and fat malabsorption, vitamin D deficiency, bone loss, and nephrolithiasis. Recognition and early diagnosis of these complications are important when managing IPAA patients.
Inflammatory bowel disease; ileal pouch—anal anastomosis; metabolic consequences; anemia; vitamin B12 deficiency; vitamin D deficiency
The perioperative management of patients with inflammatory bowel disease is challenging given the altered immune system that results from a variety of biologic and immunomodulator therapies. Clinicians are often faced with challenges and complicated equations when deciding on the type and dose of medication. To understand the effect of these medications and review the evidence regarding the management of these medications in the perioperative setting, a PubMed-based literature search (January 1, 1960, through April 1, 2011) was conducted using the following search terms: perioperative management, risk, outcome, inflammatory bowel disease, ulcerative colitis, Crohn's disease, aminosalicylates, glucocorticoids, purine analogues, cyclosporine, methotrexate, biologic therapy, infliximab, and thromboembolism. The 414 articles identified were manually sorted to exclude those that did not address perioperative risk, outcomes, and medications in the abstracts, yielding 84 articles for review. Additional references were obtained from the citations within the retrieved articles. This review surveys the findings of the selected articles and presents guidelines and resources for perioperative medication management for patients with inflammatory bowel disease undergoing surgery.
Ulcerative colitis (UC) is a chronic inflammatory disease characterized by diffuse mucosal inflammation limited to the colon and rectum. Although a complete medical cure may not be possible, UC can be treated with medications that induce and maintain remission. The medical management of this disease continues to evolve with a goal to avoid colectomy and ultimately alter the natural history of UC. Emergence of antitumor necrosis factor-α (TNF-α) agents has expanded the medical armamentarium. 5-Aminosalicylates continue to be used in mild to moderate UC and corticosteroids are mainly used for induction of remission with immunomodulators (6-mercaptopurine/azathiopurine/methotrexate) being applied as steroid-sparing agents for maintenance therapy. Infliximab has been approved by the U.S. Food and Drug Administration and used in the treatment of moderate to severe UC; nevertheless, its use may be associated with significant adverse effects and have a negative impact on the postoperative course should the patients undergo restorative proctocolectomy. In addition, there is always a concern about patients' compliance to medical therapy, cost of medications, and risk for UC-associated dysplasia. The authors discuss the pros and cons of medications used in the treatment of UC.
Inflammatory bowel disease; ulcerative colitis; medical treatment; risks and benefits
Although restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the surgical treatment of choice for patients with refractory ulcerative colitis (UC) or UC with dysplasia, surgical, inflammatory, and noninflammatory adverse sequelae are common. Pouchitis, representing a spectrum of disease phenotypes, is the most common long-term complication of IPAA. De novo Crohn disease (CD) of the pouch can occur in patients with a preoperative diagnosis of UC. Differential diagnosis between fibrostenotic or fistulizing CD and surgery-associated strictures, sinuses, and fistulas often requires a combined assessment of symptom, endoscopy, histology, radiography, and examination under anesthesia. There is a role for endoscopic therapy for stricturing complications of IPAA. Chronic antibiotic-refractory pouchitis, refractory cuffitis, as well as fibrostenotic or fistulizing CD of the pouch are the leading late-onset causes for pouch failure.
Complication; ileal pouch; inflammatory bowel disease; restorative proctocolectomy
Autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high titers of autoantibodies or antigen-specific T cells, and derive from genetic variants of the innate immune system. This study characterized a cohort of patients with similar phenotypes and nucleotide oligomerization domain 2 (NOD2) gene mutations.
Diagnostically challenging patients with the following clinical and genetic characteristics were prospectively studied between January 2009 and April 2011: periodic fever, dermatitis, polyarthritis, serositis, negative serum autoantibodies and additional positive NOD2 IVS8+158 gene mutation. Genetic testing for gene mutations of NOD2, tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS) and familial Mediterranean fever (FMF) was performed.
All seven patients with the disease were Caucasians, with four being male. The mean age at disease onset was 40.7 years and disease duration was 3.2 years. These patients characteristically presented with periodic fever, dermatitis and inflammatory polyarthritis. There were gastrointestinal symptoms in three patients, granulomas of the skin and gut in two, and recurrent chest pain in two, with one having pleuritis and pericarditis. Three patients had sicca-like symptoms. Five patients had increased acute phase reactants. All seven patients had negative tests for autoantibodies but carried the NOD2 gene mutation IVS8+158 with four having concurrent R702W mutation.
Our cohort may represent a new disease category of autoinflammatory disease with characteristic clinical phenotypes and genotypes. It may somewhat resemble pediatric Blau's syndrome.
Kallistatin is a plasma protein with anti-inflammatory properties. In this study, we investigated the role and mechanisms of kallistatin in inhibiting endothelial inflammation through its heparin-binding domain. We showed that recombinant wild-type kallistatin dose-dependently competed with tumor necrosis factor (TNF)-α binding to TNF-α receptor in endothelial cells, whereas kallistatin mutant at the heparin-binding domain had no effect. Kallistatin, but not kallistatin mutant at the heparin-binding domain, abrogated TNF-α-induced endothelial cell activation as evidenced by inhibition of TNF-α receptor/TRADD activation, IκB-α degradation, nuclear factor-κB translocation and p38MAPK phosphorylation, as well as cell adhesion molecule and cytokine expression. Moreover, kallistatin, but not kallistatin mutant at the heparin-binding domain, inhibited TNF-α-induced THP-1 monocyte adhesion to endothelial cells, and prevented vascular endothelial growth factor-induced endothelial permeability. In mice, kallistatin gene delivery prevented vascular leakage provoked by complement factor C5a, whereas delivery of kallistatin heparin mutant gene had no effect. Similarly, gene transfer of kallistatin, but not the kallistatin heparin mutant, inhibited collagen/adjuvant-induced arthritis in rats. These results indicate that kallistatin's heparin–binding site plays an essential role in preventing TNF-α–mediated endothelial activation and reducing vascular endothelial growth factor-induced vascular permeability, resulting in attenuation of vascular inflammation in cultured endothelial cells and animal models. This study identifies a protective role of kallistatin in vascular injury, thereby implicating therapeutic potential of kallistatin for vascular and inflammatory diseases.
kallistatin; tumor necrosis factor-α; vascular endothelial growth factor; nuclear factor κB; inflammation; vascular permeability