Systemic lupus erythematosus is a risk factor for cancer: a nationwide population-based study in Korea.

OBJECTIVE: Specific differences in cancer risk have been observed between systemic lupus erythematosus patients and the general population. Although meta-analyses have estimated cancer incidence in systemic lupus erythematosus patients, results have been inconclusive. Hence, we aimed to assess malignancy risk in systemic lupus erythematosus patients, compared to the risk in the general population. METHODS: Systemic lupus erythematosus patients ( n = 21,016; mean age 41.67 ± 13.14 years; female 90.22%) were selected from the Korean National Health Insurance Service database between 2008 and 2014. Age- and sex-matched controls were randomly sampled in a 5:1 ratio ( n = 105,080). RESULTS: During the 7 years of follow up, malignancy was detected in 763 (3.63%) systemic lupus erythematosus patients and 2667 (2.54%) controls. Systemic lupus erythematosus patients had a higher risk of malignancy than controls (odds ratio 1.44; 95% confidence interval 1.327-1.559), after multivariate adjustment. Systemic lupus erythematosus patients had a higher odds ratio for developing cervical, thyroid, ovarian, and oral cancer, as well as lymphoma, leukemia, and multiple myeloma than controls. Based on subgroup analysis, male systemic lupus erythematosus patients and patients younger than 40 years showed the highest lymphoma risk. CONCLUSIONS: Systemic lupus erythematosus might be an independent risk factor for cancer. Therefore, the importance of cancer screening programs should be emphasized in systemic lupus erythematosus patients. Our study is the first large nationwide cohort study for evaluating the risk of cancer in systemic lupus erythematosus patients.

Fluoroscopy-assisted epidural catheter placement: an exploratory analysis of 303 pre-operative epidurograms.

BACKGROUND: Epidural catheters that are placed for post-operative analgesia have a significant failure rate in the first 24 hours. Beginning in 2011, we have used fluoroscopic guidance to place all non-obstetrical epidural catheters. In this retrospective analysis, we hypothesized that the characteristics of dye distribution on an epidurogram obtained immediately after catheter placement would predict clinical catheter function after surgery. METHODS: The epidurograms and medical records of 303 consecutive patients who had epidural catheters placed for post-operative analgesia were reviewed. We extracted data on epidural dye distribution on the epidurograms and compared these results to the clinical function of the epidural catheters assessed on post-operative day 1 (POD1). RESULTS: The three-dimensional pattern of epidural dye distribution (cephalad-caudad, right-left, anterior-posterior) had significant correlations with clinical function of an epidural catheter after surgery. Increased cephalad-caudad and anterior dye spread both correlated with decreased epidural solution infusion rates on POD1, whereas right- or left-sided dye distribution correlated with unilateral sensory deficits. A higher catheter placement on the neuraxis correlated with lower pain scores after thoracic surgery. CONCLUSIONS: An epidurogram obtained immediately after epidural catheter placement may have clinical utility for predicting clinical function of the catheter after surgery.

Haploinsufficiency of cathepsin D leads to lysosomal dysfunction and promotes cell-to-cell transmission of α-synuclein aggregates.

Lysosomal dysfunction has been implicated both pathologically and genetically in neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease (PD). Lysosomal gene deficiencies cause lysosomal storage disorders, many of which involve neurodegeneration. Heterozygous mutations of some of these genes, such as GBA1, are associated with PD. CTSD is the gene encoding Cathepsin D (CTSD), a lysosomal protein hydrolase, and homozygous CTSD deficiency results in neuronal ceroid-lipofuscinosis, which is characterized by the early onset, progressive neurodegeneration. CTSD deficiency was also associated with deposition of α-synuclein aggregates, the hallmark of PD. However, whether partial deficiency of CTSD has a role in the late onset progressive neurodegenerative disorders, including PD, remains unknown. Here, we generated cell lines harboring heterozygous nonsense mutations in CTSD with genomic editing using the zinc finger nucleases. Heterozygous mutation in CTSD resulted in partial loss of CTSD activity, leading to reduced lysosomal activity. The CTSD mutation also resulted in increased accumulation of intracellular α-synuclein aggregates and the secretion of the aggregates. When α-synuclein was introduced in the media, internalized α-synuclein aggregates accumulated at higher levels in CTSD+/- cells than in the wild-type cells. Consistent with these results, transcellular transmission of α-synuclein aggregates was increased in CTSD+/- cells. The increased transmission of α-synuclein aggregates sustained during the successive passages of CTSD+/- cells. These results suggest that partial loss of CTSD activity is sufficient to cause a reduction in lysosomal function, which in turn leads to α-synuclein aggregation and propagation of the aggregates.

Clinical Features and Prognosis of Invasive Pulmonary Aspergillosis in Korean Children with Hematologic/Oncologic Diseases.

Invasive pulmonary aspergillosis (IPA) is the most frequent form of invasive fungal diseases in immunocompromised patients. However, there are only a few studies on IPA in immunocompromised children in Korea. This study was designed to characterize IPA in Korean children with hematologic/oncologic diseases. Medical records of children with hematologic/oncologic diseases receiving antifungal therapy were reviewed. The enrolled children were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups. During the study period, 265 courses of antifungal therapy were administered to 166 children. Among them, two (0.8%) episodes of proven IPA, 35 (13.2%) of probable IPA, and 52 (19.6%) of possible IPA were diagnosed. More children in the IPA group suffered from neutropenia lasting for more than two weeks (51.4% vs. 21.9%, P<0.001) and showed halo signs on the chest computed tomography (78.4% vs. 40.7%, P<0.001) than in the non-IPA group. No other clinical factors showed significant differences between the two groups. Amphotericin B deoxycholate was administered as a first line antifungal agent in 33 (89.2%) IPA group episodes, and eventually voriconazole was administered in 27 (73.0%) episodes. Ten (27.0%) children in the IPA group died within 12 weeks of antifungal therapy. In conclusion, early use of chest computed tomography to identify halo signs in immunocompromised children who are expected to have prolonged neutropenia can be helpful for early diagnosis of IPA and improving prognosis of children with IPA.

Prognostic impact of hyponatraemia in patients with colorectal cancer.

AIM: Hyponatraemia is a common in surgical practice, but its clinical impact in patients with colorectal cancer has not been evaluated. METHOD: We retrospectively assessed 2944 patients who had been admitted to Chonnam National University Hwasun Hospital, Korea with a diagnosis of colorectal cancer. In order to determine the relationship between the serum sodium level and 3-year mortality, we categorized the patients as having normonatraemia (135-147 mEq/l), or mild (130-134 mEq/l), moderate (125-129 mEq/l) or severe hyponatraemia (< 125 mEq/l). RESULTS: Hyponatraemia, defined as a serum sodium level of < 135 mEq/l, was evident in 27.6% of patients during hospitalization. Declining serum sodium levels were associated with increasing age, a higher number of comorbidities, a more advanced TNM stage and worsening biochemical parameters. In a multivariate Cox-proportional regression analysis, the mortality risk was correlated with the severity of hyponatraemia [hazard ratio (HR) 1.65, 95% CI 1.38-1.96; HR 2.24, 95% CI 1.69-2.98; HR 2.20, 95% CI 1.25-3.90, for patients with mild, moderate, and severe hyponatraemia, respectively, compared with patients with normonatraemia]. An independent association between hyponatraemia and long-term mortality was sustained among various subpopulations and patients with persistent hyponatraemia had a worse prognosis than those with hyponatraemia that resolved. CONCLUSION: A substantial proportion of patients developed hyponatraemia during hospitalization, and the long-term mortality risk increased even in mild cases of hyponatraemia. Hyponatraemia should be considered as an important prognostic factor in colorectal cancer.

Bullous cutaneous mastocytosis, a rarely reported disease in Asian children.

Diffuse cutaneous mastocytosis, the most rare form of cutaneous mastocytosis, often manifests as bullous lesions. Although cutaneous mastocytosis should be included in a differential diagnosis for pruritic skin lesions in children, early diagnosis of the disease is not easy due to its rare occurrence. A 17-month-old boy presented with recurrent itchy bullous skin lesions. He had been treated as atopic dermatitis at other hospitals for about one year, however, he was eventually diagnosed with diffuse cutaneous mastocytosis through skin biopsy. Unlike adults, children with cutaneous mastocytosis usually improve with age and do not develop systemic mastocytosis. Therefore, early and accurate diagnosis of cutaneous mastocytosis in children is essential for appropriate care.

Use of intravenous immunoglobulin in a disseminated varicella infection in an immunocompromised child.

Varicella-zoster virus infection can lead to severe illness in immunocompromised patients. Further the mortality rate of disseminated varicella infection is extremely high particularly in immunocompromised children. We report a case of disseminated varicella infection in a child with acute lymphoblastic leukemia who was receiving chemotherapy, but was initially admitted with only for acute abdominal pain. The patient rapidly developed severe complications, including acute respiratory distress syndrome, acute hepatitis, disseminated intravascular coagulation, and encephalopathy. Acyclovir is a highly potent inhibitor of varicella-zoster virus infection. However, owing to rapid disease progression, it might not be sufficient to control a disseminated varicella infection, especially in immunocompromised patients. Immunoglobulin neutralize virus invasion and suppress viremia, acting synergistically with acyclovir. In this case, early administration of acyclovir and a high-dose of immunoglobulin, combined with mechanical respiratory support, proved adequate for treatment of this severe illness.

Features of Epstein-Barr virus reactivation after allogeneic hematopoietic cell transplantation in Korean children living in an area of high seroprevalence against Epstein-Barr virus.

The present study was conducted to investigate Epstein-Barr virus (EBV) reactivation after hematopoietic cell transplantation (HCT) in Korean children living in an area of a high seroprevalence against EBV and to determine the impact of recipient age on EBV reactivation. Medical records of 248 children and adolescents who had received allogeneic HCT were retrospectively reviewed. The trends of EBV reactivation and post-transplant lymphoproliferative disorders (PTLDs) were evaluated and compared between younger (≤10 years old) and older (11-20 years old) groups. EBV reactivation occurred in 177 cases (71.4 %) and high-level EBV reactivation, defined as a virus DNA titer of 300,000 copies/mL or higher, occurred in 21 cases (8.5 %). PTLD was diagnosed in five cases (2.0 %), and one of these patients died. The EBV reactivation rate was not significantly different between the two age groups; however, high-level reactivation and PTLD were more significantly frequent in the older than in the younger group (P = 0.030 and P = 0.026, respectively). In conclusion, older children and adolescents are more likely to experience high-level EBV reactivation and PTLDs, and higher EBV DNA titers than those previously reported may be a predictor of PTLD in areas with a high seroprevalence against EBV.

Recurrent lymphadenopathy in children with Kikuchi-Fujimoto disease.

UNLABELLED: Kikuchi-Fujimoto disease (KFD) is characterized by self-limiting regional lymphadenopathy with prolonged fever. Although the reported recurrence rate of KFD is known to be 3-4 %, this rate appears to be higher in our clinical experience, and rates up to 38.5 % have been previously reported. In this retrospective study, we reviewed medical records of children with pathologically confirmed KFD to investigate the factors associated with recurrent KFD. Enrolled children were divided into two groups according to the recurrence of KFD, and clinical and laboratory factors were compared between the two groups. The recurrence of KFD was determined based not on repeated pathologic confirmation but on the presence of clinical febrile lymphadenopathy. A total of 33 children with KFD, 26 boys (78.8 %) and 7 girls (21.2 %), with a median age of 12 years (9 months to 19 years), were enrolled. Thirty-one children (93.9 %) complained of fever, and most of the children (90.9 %) complained of cervical lymphadenopathy. Neutropenia (<1,500/µL) or lymphopenia (<1,500/µL) was observed in 51.5 %. Lactate dehydrogenase level, erythrocyte sedimentation rate, and C-reactive protein level were elevated in 90.9, 96.9, and 54.5 % of children, respectively. Fourteen children (42.4 %) experienced recurrent KFD, including ten children after biopsy and four children before and after biopsy. In a multivariate analysis, a past history of other systemic illnesses (p = 0.013) and a higher absolute lymphocyte count (p = 0.023) were significantly associated with recurrent KFD. These systemic illnesses were chronic idiopathic thrombocytopenic purpura, autoimmune thyroiditis, nephrotic syndrome, perinatal cytomegalovirus infection, and hemophagocytic lymphohistiocytosis. CONCLUSION: Our results suggest that recurrent KFD is more frequent than reported, and recurrent KFD should be considered in children with a history of other systemic illnesses such as immune disorders.

Phospholipase D1 regulates autophagic flux and clearance of α-synuclein aggregates.

Many neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterized by abnormal accumulations of aggregated proteins. Brains in these diseases also show accumulation of autophagic vesicles in the neuronal cytoplasm, suggesting impairment of the autophagic process. As autophagy involves de novo membrane production and vesicle fusion, extensive changes in lipid molecules are necessary. However, the involvement of signaling lipid-modifying enzymes in autophagy and their roles in neurodegenerative diseases are not clear. Using specific inhibitor, we show that loss of phospholipase D1 (PLD1) activity resulted in an accumulation of microtubule-associated protein light chain 3 (LC3), p62, and polyubiquitinated proteins, signs representing malfunction in autophagic flux. Fluorescence and electron microscopic analyses demonstrated impaired fusion of autophagosomes with lysosomes, resulting in accumulation of autophagosomes. Within the cells with impaired autophagic flux, α-synuclein aggregates accumulated in autophagosomes. Knockdown of PLD1 expression using small interfering RNA also resulted in impaired autophagic flux and accumulation of α-synuclein aggregates in autophagosomes. Neuronal toxicity caused by α-synuclein accumulation was rescued by overexpression of PLD1; however, expression of activity-deficient mutant, PLD1-KRM, showed reduced rescue effects. Finally, we demonstrated that both PLD activity and expression levels were reduced in brain tissues of dementia with Lewy bodies (DLB) patients, whereas the amounts of α-synuclein and p62 were increased in the same tissue samples. Collectively, these results suggest that insufficient PLD activity, and therefore, the changes in phospholipid compositions within membranes, might be an important contributor to impaired autophagic process and protein accumulation in Lewy body diseases.

Clinical characteristics and antimicrobial susceptibilities of viridans streptococcal bacteremia during febrile neutropenia in patients with hematologic malignancies: a comparison between adults and children.

BACKGROUND: This study was performed to compare the clinical characteristics and antibiotic susceptibilities of viridans streptococcal bacteremia (VSB) between febrile neutropenic adults and children with hematologic malignancies. METHODS: The consecutive medical records of neutropenic patients with hematologic malignancies who were admitted to the Catholic Blood and Marrow Transplantation Center between April 2009 and July 2012, and who were subsequently diagnosed with VSB were reviewed retrospectively. A comparison was made between the clinical and laboratory characteristics of adults and pediatric patients and also between patients with cefepime susceptible or not susceptible VSB. RESULTS: A total of 202 episodes (141 in adults, 61 in children) of VSB were identified. Among them, 26 (12.9%) cases had severe complications including four (2.0%) cases of death attributable to VSB. For antibacterial prophylaxis, most adults received ciprofloxacin (97.1%), but children more frequently received trimethoprim/sulfamethoxazole (86.9%). Oral mucositis (p = 0.005) and abdominal pain (p = 0.001) were found more frequently in adults, and cough was found more frequently in children (p = 0.004). The occurrence rates of severe complications and death attributable to VSB were not significantly different between adults and children. Susceptibility rate to cefepime was significantly higher in adults than children (85.7% vs. 66.1%, p = 0.002). However, in multivariate analysis, cefepime susceptibility had no impact on clinical outcome. CONCLUSIONS: There was no significant difference in clinical outcome between adults and children with VSB despite a difference in cefepime susceptibility. Hence, different antibiotic treatment strategies may not be necessary.

Differential diagnosis of myelofibrosis based on WHO 2008 criteria: acute panmyelosis with myelofibrosis, acute megakaryoblastic leukemia with myelofibrosis, primary myelofibrosis and myelodysplastic syndrome with myelofibrosis.

INTRODUCTION: The aim of this study was to characterize clinicopathological features of acute panmyelosis with myelofibrosis (APMF), acute megakaryoblastic leukemia with myelofibrosis (AMKL-MF), primary myelofibrosis (PMF) and myelodysplastic syndrome with myelofibrosis (MDS-MF) in order to provide the keys to the differential diagnosis of bone marrow (BM) fibrosis. METHODS: We compared age, gender, splenomegaly, serum lactate dehydrogenase level, blood cell counts, blast counts in peripheral blood (PB) and BM, megakaryocyte counts, BM cellularity, dysplasia, and the karyotypes of patients with APMF (n = 6), AMKL-MF (n = 7), PMF (n = 44), and MDS-MF (n = 44). RESULTS: APMF showed hyperplasia of all three lineages, increase in megakaryocyte count with dysplasia and frequent abnormal karyotypes. AMKL-MF was associated with elevated BM blast counts, decreased BM megakaryocyte count with rare megakaryocytic dysplasia and chromosome 21 abnormality. PMF patients displayed splenomegaly, rare blasts in PB/BM, and JAK2 V617F mutation. MDS-MF patients showed pancytopenia, dysplasia in all three lineages and recurrent chromosomal abnormalities involving chromosome 5,7,12, and 17. CONCLUSIONS: Although differential diagnosis among APMF, AMKL-MF, PMF, and MDS-MF is very challenging due to the overlapping clinical and morphological features, meticulous investigation of the patient with respect to splenomegaly, blood cell count, PB and BM findings, and karyotype will serve as a guide to correct diagnosis.

Clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia in children with febrile neutropenia.

PURPOSE: This retrospective study was performed in order to investigate the clinical characteristics and antibiotic susceptibility of viridans streptococcal bacteremia (VSB) in febrile neutropenic children in the context of the increase in incidence and antibiotic resistance of VSB. METHODS: We conducted this study among neutropenic children with underlying hematology/oncology diseases who were diagnosed with VSB at a single institution from April 2009 to June 2012. Clinical and laboratory characteristics of the children as well as antibiotic susceptibility of the causative viridans streptococci were evaluated. RESULTS: Fifty-seven episodes of VSB were diagnosed in 50 children. Severe complications occurred in four children (7.0%), and a death of one child (1.8%) was attributable to VSB. Acute myeloid leukemia was the most common underlying disease (70.2% of all cases), and 71.9% of all cases received chemotherapy including high-dose cytarabine. VSB occurred at a median of 13 days (range 8-21 days) after the beginning of chemotherapy, and fever lasted for a median of 4 days (range 1-21 days). The C-reactive protein level significantly increased within a week after the occurrence of VSB (p < 0.001) and the maximum C-reactive protein level showed a positive correlation with fever duration (r = 0.362, p = 0.007). Second blood cultures were done before the use of glycopeptides in 33 children, and negative results were observed in 30 children (90.9%). Susceptibilities to cefotaxime, cefepime, and vancomycin were 58.9, 69.1, and 100%, respectively. CONCLUSIONS: Severe complications of VSB in neutropenic febrile children were rare. We suggest glycopeptide use according to the results of blood culture and antibiotic susceptibility tests based on the susceptibility to cefepime and the microbiologic response to empirical antibiotic treatment not including glycopeptides in this study.

A case of isolated bilateral pulmonary arterial calcification diagnosed in utero.

We report a very rare case of isolated multiple pulmonary arterial calcification with severe bilateral peripheral pulmonary arterial stenosis diagnosed in utero. Despite treatment with bisphosphonate for 6 months, systolic right ventricular pressure increased persistently and surpassed left ventricular pressure. After successful bilateral pulmonary arterioplasty at 13 months of age, the patient showed decreased systolic right ventricular pressure with normal interventricular septal configuration. This is the first case report for an isolated pulmonary artery calcification without other arterial calcification proven by non-contrast computed tomography of a living patient.

Mannitol facilitates neurotrophic factor up-regulation and behavioural recovery in neonatal hypoxic-ischaemic rats with human umbilical cord blood grafts.

We recently demonstrated that blood-brain barrier permeabilization using mannitol enhances the therapeutic efficacy of systemically administered human umbilical cord blood (HUCB) by facilitating the entry of neurotrophic factors from the periphery into the adult stroke brain. Here, we examined whether the same blood-brain barrier manipulation approach increases the therapeutic effects of intravenously delivered HUCB in a neonatal hypoxic-ischaemic (HI) injury model. Seven-day-old Sprague-Dawley rats were subjected to unilateral HI injury and then at day 7 after the insult, animals intravenously received vehicle alone, mannitol alone, HUCB cells (15k mononuclear fraction) alone or a combination of mannitol and HUCB cells. Behavioural tests at post-transplantation days 7 and 14 showed that HI animals that received HUCB cells alone or when combined with mannitol were significantly less impaired in motor asymmetry and motor coordination compared with those that received vehicle alone or mannitol alone. Brain tissues from a separate animal cohort from the four treatment conditions were processed for enzyme-linked immunosorbent assay at day 3 post-transplantation, and revealed elevated levels of GDNF, NGF and BDNF in those that received HUCB cells alone or when combined with mannitol compared with those that received vehicle or mannitol alone, with the combined HUCB cells and mannitol exhibiting the most robust neurotropic factor up-regulation. Histological assays revealed only sporadic detection of HUCB cells, suggesting that the trophic factor-mediated mechanism, rather than cell replacement per se, principally contributed to the behavioural improvement. These findings extend the utility of blood-brain barrier permeabilization in facilitating cell therapy for treating neonatal HI injury.

Dental panoramic radiographic evaluation in bisphosphonate-associated osteonecrosis of the jaws.

OBJECTIVES: To determine the extent to which clinical and radiographic features of bisphosphonate-associated osteonecrosis of the jaw (BONJ) are correlated. DESIGN: Retrospective case review. METHODS: The records of 39 patients diagnosed with BONJ and examined by panoramic radiography were retrospectively evaluated. The arches were divided into sextants (n = 234) and evaluated for the following signs: sclerosis, surface irregularity, sockets, fragmentation and lysis. MAIN OUTCOME MEASURES: The McNemar, Kruskall-Wallis and equivalency tests were performed to analyze the association between clinical and radiographic signs and BONJ severity. RESULTS: Sixty-two out of 234 sextants were abnormal by clinical criteria and 61 out of 234 sextants demonstrated at least one radiographic abnormality. There was agreement between clinical and radiographic detection in 41 sextants. The data showed equivalency between BONJ diagnosis and both sclerosis and surface irregularity. The correlation between number of clinical sites and any radiographic finding was significant in the maxilla (P < 0.001) but not in the mandible (P = 0.178). The total number of radiographic signs per patient increased with BONJ stage. CONCLUSION: Focal panoramic radiographic findings of sclerosis and surface irregularity correlate with clinical sites of BONJ. This may be a useful and reliable tool to detect early changes of BONJ or to confirm a clinical diagnosis.

Caspase-3 activation as a key factor for HBx-transformed cell death.

OBJECTIVES: Nuclear factor-kappa B (NF-kappaB) activation has been associated with the tumorigenic growth of hepatitis B virus X protein (HBx)-transformed cells. This study was aimed to find a key target for treatment of HBx-mediated cancers. MATERIALS AND METHODS: NF-kappaB activation, endoplasmic reticulum-stress (ER-stress), caspase-3 activation, and cell proliferation were evaluated after Chang/HBx cells permanently expressing HBx viral protein were treated with inhibitors of NF-kappaB, proteasome and DNA topoisomerase. RESULTS: Inhibition of NF-kappaB transcriptional activity by transient transfection with mutant plasmids encoding Akt1 and glycogen synthase kinase-3beta (GSK-3beta), or by treatment with chemical inhibitors, wortmannin and LY294002, showed little effect on the survival of Chang/HBx cells. Furthermore, IkappaBalpha (S32/36A) mutant plasmid or other NF-kappaB inhibitors, 1-pyrrolidinecarbonidithioic acid and sulphasalazine, were also shown to have little effect on the cell proliferation. By contrast, proteasome inhibitor-1 (Pro1) and MG132 enhanced the HBx-induced ER-stress response and the subsequent activation of caspase-12, -9 and -3 and reduced cell proliferation. Camptothecin (CPT), however, triggered activation of caspase-3 without induction of caspase-12, and reduced cell proliferation. In addition, CPT-induced cell death was reversed by pre-treatment with z-DEVD, a caspase-3-specific inhibitor. CONCLUSIONS: Detailed exploitation of the regulators of caspase-3 activation could open the gate for finding an efficient target for development of anticancer therapeutics against HBx-transformed hepatocellular carcinoma.

Microencapsulation of avocado oil by spray drying using whey protein and maltodextrin.

Cold pressed avocado oil was microencapsulated by spray drying in four different wall systems consisting of whey protein isolate (WPI) alone or in combination with maltodextrin (MD) DE 5 at various ratios (90 : 10, 50 : 50 and 10 : 90). The WPI only or WPI/MD (90 : 10) powders were spherical and smooth, whereas the WPI/MD (50 : 50 and 10 : 90) powders exhibited pronounced surface collapse. Increasing the MD ratio resulted in higher bulk density and wettability, probably due to more compact physical structure and hydrophilic wall matrix. Surface free oil contents and microencapsulation efficiencies of powders were 11-16% and 45-66%, respectively, and no significant differences were observed between the samples. The crude avocado oil used in this study appeared to be stable against oxidation at cold and ambient temperatures, irrespective of microencapsulation. However, at high temperature of 60 degrees C, the oxidative stability decreased significantly in all cases but it was improved to some extent by microencapsulation.

Glucocorticoid-induced tumour necrosis factor receptor-related protein-mediated macrophage stimulation may induce cellular adhesion and cytokine expression in rheumatoid arthritis.

Glucocorticoid-induced tumour necrosis factor receptor (TNFR)-related protein (GITR) is one of the T cell co-stimulatory molecules and is associated with the pathogenesis of a number of autoimmune diseases. We investigated the expression patterns of GITR in human arthritic synovium and the role of GITR in the pathogenesis of rheumatoid arthritis (RA). Immunohistochemical analyses revealed the expression of GITR and its cognate ligand, GITRL, in macrophages in RA, but not in osteoarthritis (OA), synovium. To investigate the role of GITR in macrophage functions, primary macrophages from RA patients and a human macrophage cell line, THP-1, were analysed. Stimulation of the macrophages with anti-GITR monoclonal antibody induced up-regulation of intercellular adhesion molecule (ICAM)-1 and subsequent aggregation/adhesion, which was enhanced by the presence of extracellular matrix proteins and blocked by anti-ICAM-1 monoclonal antibody. The validity of these in vitro observations was confirmed by immunohistochemical analyses of RA synovium, which showed strong expression of ICAM-1 in GITR-positive macrophages. Additionally, GITR stimulation induced expression of proinflammatory cytokines/chemokines and matrix metalloproteinase-9 in synovial macrophages. These data indicate that GITR, expressed on macrophages in human RA synovium, may enhance inflammatory activation of macrophages by promoting cytokine gene expression and adhesion between cells and to extracellular matrix in RA synovium.

The effects of curcumin on the invasiveness of prostate cancer in vitro and in vivo.

Curcumin has become a focus of interest with regard to its antitumor effects in prostate cancer; however, the effects of this agent on invasion and metastasis remain less well understood. Matrix metalloproteinases (MMPs) are important prerequisite for tumor invasion and metastasis. In this study, we evaluated the effects of curcumin on prostate cancer cells (DU-145) invasion in both in vitro and in vivo. We utilized zymography and ELISA in order to determine the MMP-2 and MMP-9 activity. Matrigel invasion assay was performed to assess cellular invasion. We developed a xenograft model to examine tumorigenicity. Curcumin treatment resulted not only in a significant reduction in the expression of MMP-2 and MMP-9, but also effected the inhibition of invasive ability in vitro. Curcumin was shown to induce a marked reduction of tumor volume, MMP-2, and MMP-9 activity in the tumor-bearing site. The metastatic nodules in vivo were significantly fewer in the curcumin-treated group than untreated group. Curcumin appears to constitute a potential agent for the prevention of cancer progression, or at least of the initial phase of metastasis, in prostate cancer.