Effects of Glycyrrhiza polysaccharide in diet on growth performance, serum antioxidant capacity, and biochemistry of broilers.

In the present study, we analyzed the effects of Glycyrrhiza polysaccharide (GCP) on growth performance, serum antioxidant capacity, and biochemistry of broilers. A total of 600, one-day-old AA broilers randomly divided into 5 treatment groups with 6 replicate pens of 20 birds per cage received dietary supplementation with GCP (0, 200, 500, 1,000, and 1,500 mg/kg) for 42 d. The supplementation of GCP linearly decreased (P < 0.05) feed conversion rate on day 22 to 42. Dietary supplementation with GCP reduced (P < 0.05) serum total cholesterol on day 21 and 42 and linearly improved (P < 0.05) albumin and high-density lipoprotein cholesterol. Dietary supplementation with 1,000 or 1,500 mg/kg GCP significantly increased (P < 0.05) serum total superoxide dismutase (T-SOD) activity on day 21 and 42 and reduced (P < 0.05) serum malondialdehyde content on 21 d. Dietary supplementation with 1,000 or 1,500 mg/kg GCP significantly improved (P < 0.05) interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ) expressions in liver on day 21 and 42. At the end of the experiment, we randomly selected 20 broilers from 3 treatment groups (0, 1,000, and 1,500 mg/kg), respectively, to perform an lipopolysaccharide (LPS)-induced acute stress experiment. The 60 broilers were divided into 6 treatment groups with 10 birds per cage. The experiment was designed as a 3 × 2 factorial arrangement with GCP (0, 1,000, or 1,500 mg/kg) and LPS (injection of saline or 1 mg/kg body weight) levels as treatments. When the grouping was finished, the broilers were immediately intraperitoneally injected with LPS or normal saline. Six hours after challenged, serum antioxidant and liver immunity were analyzed. The results showed that dietary GCP prevented LPS-induced reductions in T-SOD activity and increases in malonaldehyde content (P < 0.05). Also, dietary GCP supplementation mitigated the LPS-induced increase in IL-1ß and IFN-γ in the liver. Supplementation with 1,500 mg/kg GCP showed the most optimal effect in broilers. GCP has the potential to be used as feed additive in broilers.

Survival Outcomes of Oversized Cardiac Allografts in Pediatric Patients-A Single-Center Experience in Taiwan.

OBJECTIVES: An oversized cardiac allograft may have a negative impact on survival outcomes according to previous studies; however, due to the shortage of pediatric donor hearts, the use of oversized cardiac allografts is sometimes inevitable. In this study, we reported the survival outcomes of pediatric patients in relation with the donor-recipient weight ratio. METHODS: Twenty-eight children, aged 3 months to 17 years, with dilated cardiomyopathy underwent primary cardiac transplantation at the National Taiwan University Hospital between 1995 and 2012. We analyzed these patients according to the donor-recipient weight ratio: group 1 (n = 19) with donor-recipient weight ratio <2.5 (median 1.1, interquartile range 1.0-1.6), and group 2 (n = 9) with donor-recipient weight ratio ≥2.5 (median 3.0, inter-quartile range 2.87-3.5). RESULTS: The 30-day survival rate was 100% for both group 1 and group 2 (P = 1). The survival rates for group 1 and group 2 were 95% vs 100% at 1 year, 84% vs 89% at 5 years, and 73% vs 61% at 10 years. The median survival was 14.4 years vs 12.9 years (P = .6313). CONCLUSION: In this cohort, the use of oversized cardiac allograft in pediatric patients for dilated cardiomyopathy did not have a negative effect on short-term and long-term survival.

Changes in Renal Function After Heart Transplantation.

Renal function after heart transplantation (HTx) typically follows a biphasic pattern and an initial decay within 1 to 2 years. Trajectory of renal function after HTx is less reported, especially in Asia. The aims of this cohort study were to describe the changes in HTx recipients' serum creatinine and estimated glomerular filtration rate (eGFR) levels 5 years following HTx in Taiwan. METHODS: We retrospectively reviewed 5 years of 440 consecutive adult patients (≥ 18 years) who underwent first HTx from June 1987 to December 2014 at the National Taiwan University Hospital. RESULTS: Among 422 participants, they received induction therapy consisting of intravenous rabbit antithymocyte globulin. Here, we illustrated the trends over the years by dividing the subjects into 2 groups based on their immunosuppressive regimen of transplantation (1987-2002 and 2003-2014) The pretransplantation median serum creatinine concentration level was 1.2 mg/dL, rose to 1.4 mg/dL at 3 months after surgery, and remained steady over 5 years after HTx. Pretransplant median eGFR was 67 mL/min/1.73 m2.The median serum creatinine concentration level and eGFR at baseline were all significantly difference than pretransplantation (P > .05). This result has showed that an initial steep decline within 3 months after transplant remained stable 5 years after HTx. CONCLUSION: As renal function deteriorates after HTx, we observed a steep decline in serum creatinine level and glomerular filtration rate within the 3 months after HTx, followed by a slow rate of deterioration over the following months. We found a time-related progressive deterioration in renal function during the 5 years after HTx.

Characterization of titanium dioxide and zinc oxide nanoparticles in sunscreen powder by comparing different measurement methods.

Numerous consumer products, such as cosmetics, contain nanoparticles (NPs) of titanium dioxide (TiO2) or zinc oxide (ZnO); however, this raises questions concerning the safety of such additives. Most of these products do not indicate whether the product includes NPs. In this study, we characterized metal oxide NPs according to size, shape, and composition as well as their aggregation/agglomeration characteristics. In order to comprehend quickly the characterization of metal oxide NPs, we employed single particle inductively coupled plasma (SP-ICPMS) to help quantify the size of metal oxide NPs; then, we use transmission electron microscopy (TEM) to corroborate the results. The crystal size and structure was measured by X-ray diffraction (XRD), there are two crystal phase of TiO2 NPs in sunscreen powder showed in XRD. However, SP-ICPMS proved highly effective in determining the size of NPs, the results of which remarkably good agreement with the TEM measurements. Pre-treatment included a conventional copper grid (requiring sample dilution) to evaluate the size, shape and composition of primary particles or plastic embedding (without the need for sample dilution) to evaluate the aggregate/aggregation of native NOAAs. The proposed method is an effective and fast approach to the characterization of oxide NPs in cosmetic sunscreen powder. These findings outline an alternative approach to the analysis of NPs in powder-form matrix.

Human Polyomavirus Is Associated With Earlier Onset of Upper Urinary Tract Urothelial Carcinoma in Patients After Kidney Transplantation.

OBJECTIVES: Polyomavirus has been reported to be oncogenic due to viral integration into the human genome. A relatively high prevalence of upper urinary tract urothelial carcinoma (UTUC) was noted after kidney transplantation (KT) in Taiwan. However, little was known about the impact of polyomavirus on the urothelial cancer behavior. Therefore, the aim of this study is to analyze the characteristics of polyomavirus-related UTUC after KT. METHODS: From 2005 to 2014, 27 patients were found to have UTUCs after KT. All the patients underwent standard nephroureterectomy. Detailed perioperative parameters were obtained from chart records. A qualified pathologist who is blinded to the clinical outcome examined large T antigen expression and pathological features. All the patients were divided into two groups according to positive or negative expression of large T antigen. RESULTS: In the patient demography, a significantly younger median age was found in patients with large T antigen-positive UTUCs compared with the negative control group (48.1 ± 8.3 years versus 54.6 ± 4.1 years, respectively, P = .013). As for the pathological features and oncologic outcome, there were no obvious differences between these two groups. Non-organ-confined status and positive lymphovascular invasion are prognostic factors associated with systemic disease recurrence (P = .017 and .001, respectively). CONCLUSIONS: Although UTUC commonly develops in the elderly, earlier onset of post-KT UTUCs was observed especially in patients with positive large T antigen expression in our cohort. This preliminary result provides valuable experience suggesting more frequent upper urinary tract screening for polyomavirus infected patients after KT in Taiwan.

Molecular characterization of ascaris from Tibetan pigs by three mitochondrial markers of nad1, cox1 and cox2.

Ascaris is a helminthic parasite, which infects a wide range of host species causing ascariasis, a predominant disease worldwide. This parasite causes significant economic losses to the pig industry. The current study was designed to determine the Ascaris nematode by the genetic characterization of three mitochondrial (mt) genes namely NADH dehydrogenase subunit 1 (nad1), cytochrome oxidase subunit 1 (cox1) and cytochrome oxidase subunit 2 (cox2). A high infection rate of Ascaris nematode has been found in Tibetan pigs at the slaughter houses in Tibet Autonomous Region of China. The nad1, cox1 and cox2 genes sequences collected from adult Ascaris individuals were amplified by polymerase chain reaction. The cloned-amplicons and the positive products were sequenced and phylogenetic analysis was performed. The results indicated that the Ascaris infecting the Tibetan pigs were Ascaris suum (A. suum). This is the first report on the isolation, identification and genetic characterization of three mitochondrial genomes (nad1, cox1, and cox2) of A. suum originated from Tibetan pigs at high altitudes in Tibet.

Molecular characterization of ascaris from Tibetan pigs by three mitochondrial markers of nad1, cox1 and cox2

Ascaris is a helminthic parasite, which infects a wide range of host species causing ascariasis, a predominant disease worldwide. This parasite causes significant economic losses to the pig industry. The current study was designed to determine the Ascaris nematode by the genetic characterization of three mitochondrial (mt) genes namely NADH dehydrogenase subunit 1 (nad1), cytochrome oxidase subunit 1 (cox1) and cytochrome oxidase subunit 2 (cox2). A high infection rate of Ascaris nematode has been found in Tibetan pigs at the slaughter houses in Tibet Autonomous Region of China. The nad1, cox1 and cox2 genes sequences collected from adult Ascaris individuals were amplified by polymerase chain reaction. The cloned-amplicons and the positive products were sequenced and phylogenetic analysis was performed. The results indicated that the Ascaris infecting the Tibetan pigs were Ascaris suum (A. suum). This is the first report on the isolation, identification and genetic characterization of three mitochondrial genomes (nad1, cox1, and cox2) of A. suum originated from Tibetan pigs at high altitudes in Tibet.

The different effects of probiotics treatment on Salmonella-induced interleukin-8 response in intestinal epithelia cells via PI3K/Akt and NOD2 expression.

Salmonella spp. remains a major public health problem for the whole world. Intestinal epithelial cells serve as an essential component of the innate mucosal immune system to defend against Salmonella infection. A substantial amount of evidence has accumulated that probiotics can regulate interleukin 8 (IL-8) involved in innate immunity. However, the exact effect of probiotics on epithelial IL-8 response to Salmonella infection is not well understood. Therefore, we investigated the action of probiotics on Salmonella-infected Caco-2 cells and its novel mechanisms. Two probiotic strains were examined for Salmonella-induced IL-8 responses and regulating proteins using Caco-2 cell cultures. We demonstrated probiotic, either Lactobacillus rhamnosus GG or Bifidobacterium animalis subsp. lactis DSM10140, administered before Salmonella infection conferred significantly suppressive effect on Salmonella-induced IL-8 responses in Caco-2 cells, either in secreted protein or mRNA, via the PI3K/Akt signal pathway while probiotic administered after infection enhanced Salmonella-induced IL-8 responses via nucleotide-binding oligomerisation domain-containing protein 2 expression in membrane. These findings suggest that the different regulation of probiotics on Salmonella-induced IL-8 responses in Caco-2 cells according to the administered timing supports a rationale for the therapeutic use of probiotics in the treatment of Salmonella colitis and inflammatory bowel disease. This can explain the reported controversial effect of probiotics on these diseases.

The comparative, long-term effect of the Salter osteotomy and Pemberton acetabuloplasty on pelvic height, scoliosis and functional outcome.

AIMS: This study compared the long-term results following Salter osteotomy and Pemberton acetabuloplasty in children with developmental dysplasia of the hip (DDH). We assessed if there was a greater increase in pelvic height following the Salter osteotomy, and if this had a continued effect on pelvic tilt, lumbar curvature or functional outcomes. PATIENTS AND METHODS: We reviewed 42 children at more than ten years post-operatively following a unilateral Salter osteotomy or Pemberton acetabuloplasty. We measured the increase in pelvic height and the iliac crest tilt and sacral tilt at the most recent review and at an earlier review point in the first decade of follow-up. We measured the lumbar Cobb angle and the Short Form-36 (SF-36) and Harris hip scores were collected at the most recent review. RESULTS: During the first decade of follow-up, there was a greater increase in pelvic height in the children who had a Salter osteotomy (Salter, 10.1%; Pemberton, 4.3%, p < 0.001). The difference in the increase in pelvic height was insignificant at the most recent review (Salter, 4.4%; Pemberton, 3.1%, p = 0.249). There was no significant difference between the two groups for the lumbar Cobb angle, (Salter, 3.1°; Pemberton, 3.3°, p = 0.906). A coronal lumbar curve was seen in 41 children (97%), 30 of these had a compensatory curve. Sacral tilt was the radiographic parameter for pelvic imbalance that correlated most with the lumbar Cobb angle (Pearson correlation co-efficient 0.59). The Harris hip score and SF-36 were good and showed no differences between the two groups. CONCLUSION: In the long-term, we found no difference in the functional results or pelvic imbalance between Salter osteotomy and Pemberton acetabuloplasty in the management of children with DDH. Cite this article: Bone Joint J 2016;98-B:1145-50.

Case Series: Heart Transplantation After Fontan Operation-Single-Center Experience.

BACKGROUND: Fontan failure (FF) occurs rarely. In patients with Fontan failure, heart transplantation is believed to be the most effective therapy. We review our experience in heart transplantations after the Fontan operation. METHODS: From July 1987 to December 2014, 4 of 513 patients underwent orthotopic heart transplantation (OHT). Among them, 4 were due to FF. We reviewed these 4 cases via retrospective chart review. Clinical history, laboratory data, surgical technique, perioperative variables, and outcomes of long-term follow-up are presented herein. The primary outcomes were hospital mortality, 1-year-survival rate, and 4-year-survival rate. The secondary outcome is the improvement in patients with protein-losing enteropathy. RESULTS: The hospital mortality rate was 0% in the 4 FF patients receiving OHT. No surgically related hemorrhage or infection was observed. The 1-year-survival rate was 100% (n = 4) and the 4-year-survival rate 50% (n = 2). One patient died of posttransplantation lymphoproliferative disorder. Hypoalbuminemia improved in 1 of 3 patients 4 months after OHT. CONCLUSIONS: Despite technical challenges, heart transplantation can be performed successfully in patients with Fontan operation. However, protein-losing enteropathy might not be resolved quickly after heart transplantation.

Malignancy After Heart Transplantation Under Everolimus Versus Mycophenolate Mofetil Immunosuppression.

BACKGROUND: With advances in immunosuppressive therapy, heart transplantation is currently recommended as the only established surgical treatment for refractory heart failure. However, chronic immunosuppression increases the risk for malignancy. Everolimus (EVR) is a potent mammalian target of rapamycin inhibitor that is used after transplantation and to treat advanced malignancies, as we have done in Taiwan after heart transplantation since 2004. Mycophenolate mofetil (MMF) and EVR are frequently used as cell-cycle inhibitors to optimize post-transplantation outcomes. METHODS: We retrospectively analyzed the characteristics and outcomes of 454 patients who received either MMF (n = 232) or EVR (n = 222) after heart transplantation at the National Taiwan University Hospital from March 1, 1990, to March 1, 2015. Patient characteristics and Kaplan-Meier survival curves were compared between groups. RESULTS: During a median follow-up of 69.2 months, malignancy was diagnosed in 27 patients receiving MMF (n = 23) or EVR (n = 4). There was a significant difference in malignancy risk between groups (9.91% vs 1.80%, P = .001). The most common malignancies were non-Hodgkin lymphoma, skin cancers, and lung squamous cell carcinoma. The 2-year overall survival after malignancy was 50% in the EVR group and 47% in the MMF group (P = .745). CONCLUSIONS: EVR treatment after heart transplant is associated with a lower risk of malignancy than is MMF treatment. The 2-year survival rate after malignancy was similar between EVR and MMF groups.

Heart Transplantation Under Mechanical Circulatory Support for Acute Fulminant Myocarditis With Cardiogenic Shock: 10 Years' Experience of a Single Center.

BACKGROUND: Acute fulminant myocarditis with intractable cardiogenic shock is a fatal condition; its only therapeutic option is mechanical circulatory support. The use of mechanical circulatory support, either extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD), serves as a bridge to recovery or as a bridge to transplantation. OBJECTIVES: The aim of this research was to advance our understanding of the outcome of heart transplantation under mechanical support for acute myocarditis. Two groups of patients were compared: those recovered without undergoing transplantation and those who underwent transplantation. METHODS: We reviewed 134 patients experiencing acute myocarditis who required mechanical circulatory support (including ECMO and/or VAD) in our institute between 1994 and 2014. Demographic data, clinical characteristics, support duration, and outcome of individuals were retrospectively analyzed. RESULTS: Patients taking part in this study were aged from 1 month to 70 years, with an average age of 28 years. The transplantation-free survival rate in adults was 54%. A total of 6 adult patients receive a heart transplant under ECMO/left VAD; 2 of these patients died of uncontrolled sepsis after the heart transplantation. The duration of mechanical support ranged from 10 to 130 days (average, 41 days). CONCLUSIONS: Mechanical circulatory support in patients with acute myocarditis proved to be effective. Approximately one half of all adult patients in this study experienced myocardium recovery under mechanical support, with only 5% undergoing a successful heart transplantation. In terms of patients who survived after heart transplantation, the mid-term and long-term outcomes are favorable.

Low Incidence of Malignancy After Heart Transplantation in Taiwan.

BACKGROUND: Malignancy is the leading cause of death in Taiwan. The risk of malignancy is higher in heart transplant recipients than in the general population. We reviewed the malignancy incidence among the patients who underwent heart transplantation (HT) at the National Taiwan University Hospital (NTUH) during the past 28 years. We found that the incidence of malignancy is low in Taiwan and that the pattern of malignancy is different from that in the Western population. METHODS: From July 1987 to March 2015, 518 patients underwent HT at NTUH. Forty-four patients who died within 1 month after transplantation were excluded from this study. Thus, a total of 476 patients were enrolled in this study. There were 393 male and 83 female patients, with a mean age of 45 years at transplantation. The major indications for HT were dilated cardiomyopathy (52%) and ischemic cardiomyopathy (33%). After HT, all patients received triple immunosuppressive therapy, including a calcineurin inhibitor (cyclosporine or tacrolimus), cell-cycle inhibitor (azathioprine, mycophenolate mofetil, or everolimus), and steroid. After 1995, induction with rabbit anti-human thymocyte globulin was routinely performed. Survival was estimated by means of the Kaplan-Meier method. RESULTS: Twenty-seven patients without pre-transplantation malignancy developed malignancies after HT. The median survival time (MST) of these 27 HT patients was 76.8 months. After malignancy was diagnosed, the overall MST was 20.7 months. The 3- and 5-year overall survival rates were 44% and 27%, respectively. Twenty-one patients (77.8%) died, 10 of them because of cancer. The most common malignancy was non-Hodgkin lymphoma (n = 6), followed by skin cancer (including 2 keratoacanthomas, 2 squamous cell carcinomas, and 1 basal cell carcinoma; n = 5) and lung squamous cell carcinoma (n = 3). The univariate analysis identified cancer stage (P = .044) and comorbidity (P = .002) as factors associated with poor malignancy survival. In the multivariate analysis, comorbidity was an independent prognostic factor for greater risk of death because of post-transplantation malignancy (P = .002). CONCLUSIONS: In Taiwan, the risk of malignancy after HT is low (5.7%), as is the incidence of skin cancer. The most common malignancy was non-Hodgkin lymphoma, followed by skin cancer and lung cancer. Comorbidity was an independent factor for overall survival in cancer patients who previously underwent HT.

Surveillance of Immunosuppression During Pregnancy After Heart Transplantation: Case Report.

BACKGROUND: Transplantation and immunosuppressive drugs are major limitations to the success of pregnancy. In 1988, the first pregnancy after a heart transplant was reported, which has given female recipients the hope to give birth. During pregnancy, physiologic changes with increased blood volume and hemodilution may influence blood drug level. CASE REPORT: We reported our experience in monitoring on immunosuppressive drugs for 2 cases. Both of them underwent heart transplantation in 2006 and were 34 and 37 years old at time of pregnancy. For both cases, we frequently monitored the blood level and increased the dosage of immunosuppressive drugs accordingly. Both cases had uneventful pregnancy and delivery to healthy babies at the National Taiwan University Hospital in Taiwan. Their postpartum courses were uneventful as well. CONCLUSIONS: We advocate adjusting the immunosuppressive dosage according to the blood level before pregnancy.

Prolonged postprocedural outbreak of Mycobacterium massiliense infections associated with ultrasound transmission gel.

Postprocedural infections by Mycobacterium abscessus complex are increasing worldwide, and the source and route of transmission are infrequently identified. Here the extension of a previous clustering of paediatric patients with surgical site infections due to a single strain of the subspecies M. massiliense is reported. The investigation was conducted at a 2200-bed teaching hospital in Taiwan and included microbial surveillance of the environment (water, air, equipment and supplies) and a case-control study. We performed molecular identification and typing of the isolates by a trilocus sequencing scheme, confirmed by multilocus sequencing typing and pulsed-field gel electrophoresis. We investigated 40 patients who developed postprocedure soft tissue or bloodstream infections by M. massiliense (TPE101) during a 3-year period. Thirty-eight patients were identified at hospital A, and one newborn and her mother were identified at hospital B (185 km from hospital A). A case-control study identified the association of invasive procedures (adjusted odds ratio, 9.13) and ultrasonography (adjusted odds ratio, 2.97) (both p <0.05) with acquiring the outbreak strain. Isolates from the cases and unopened bottles of ultrasound transmission gel were all of strain ST48 and indistinguishable or closely related by pulsed-field gel electrophoresis. After replacement of contaminated gel, no new cases were detected during 18 months' follow-up. This investigation identified the use of contaminated gel as the common source causing an outbreak on a larger scale than had been recognized. Our findings halted production by the manufacturer and prompted revision of hospital guidelines.

Transcriptome sequencing and analysis of the coconut leaf beetle, Brontispa longissima.

The coconut leaf beetle, Brontispa longissima, is a destructive pest of palm plants. Although its ecological and biological characteristics are well understood, its genetic information remains largely unknown. To advance our understanding of its molecular ba-sis of biology and ecology, we sequenced and analyzed its whole transcriptome by using high-throughput Illumina paired-end sequencing technology. Approximately 8.08 Gb of clean reads were generated in a single run, which were assembled by using Trinity into 41,652 unigenes with an average length of 932 bp. By sequence similarity searches for known proteins, 23,077 (55.4%) unigenes were annotated by BLASTx searches against the NCBI non-redundant protein database. Of the unigenes assembled, 18,153 and 13,733 were assigned to Gene Ontology and Clusters of Orthologous Groups of proteins, respectively. In addition, 10,415 unigenes were mapped onto 247 pathways using the Kyoto Encyclopedia of Genes and Genomes Pathway database. These transcriptomic resources will facilitate gene identification and elucidate the molecular mechanisms of biological and ecological aspects under-lying this palm pest, in order to design a new control strategy.

Validation of the traditional Chinese version of the Menopausal Rating Scale with WHOQOL-BREF.

Objective To assess the criterion validity, construct validity and test-retest reliability of the traditional Chinese language version of the Menopause Rating Scale (MRS-TC version). Methods This was an observational, cross-sectional study covering hospital and community samples of 317 women aged 39-62 years. Two questionnaires were administered, namely, the MRS-TC version, made up of 11 items in three dimensions, and the World Health Organization Quality of Life-BREF (WHOQOL-BREF). The intraclass correlation coefficient was used to examine the test-retest reliability of the questionnaire on two separate occasions, 2 weeks apart. The internal consistency was assessed with Cronbach's α. To evaluate criterion validity, the relationship between the individual items and dimension scores of both instruments was estimated. Pearson's correlation was used to assess convergent and discriminant validity; construct validity was evaluated by comparing the mean scores of menopausal and non-menopausal women for each of the MRS dimensions. Results The final questionnaire comprised 11 items in three dimensions. The intra-class correlation (ICC) for the test-retest reliability ranged from 0.83 to 0.93; values of Cronbach's α for psychological, somatic, and urogenital symptom domains were 0.88, 0.68, and 0.59, respectively. For the convergent and discriminant validity, the correlations between the individual questionnaire and the WHOQOL-BREF were significant; those with the MRS dimensions were significantly negatively associated for the physical, psychological, social and environmental domains. Conclusion The MRS-TC version using the traditional Chinese language is a reliable and valid questionnaire for assessing menopausal symptoms and global quality of life in climacteric women.

Characterizing titanium dioxide and zinc oxide nanoparticles in sunscreen spray.

OBJECTIVE: Numerous commercial products contain titanium dioxide (TiO2 ) and zinc oxide (ZnO) nanoparticles (NPs); however, many of these are not labelled as containing NPs. This study sought to develop an effective means of characterizing TiO2 and ZnO NPs in sunscreen sprays, including the size, shape and composition of the particles as well as their aggregation/agglomeration characteristics. METHODS: Transmission electron microscopy (TEM) coupled with a window-type microchip K-kit/copper grid and X-ray diffraction (XRD) was used to characterize the oxide NPs. RESULTS: TME pre-treatment was performed using two approaches: using a conventional copper grid (requiring dilution) and using a K-kit (not requiring dilution). The use of K-kit in conjunction with XRD makes it possible to obtain direct measurements from samples that have not undergone pre-treatment, which could otherwise alter the nature of the samples, such as the degree of agglomeration. XRD was used to obtain information related to particle size and crystal structure. A strong correlation was observed between XRD and TEM measurements. CONCLUSION: The proposed measurement methods were shown to be highly effective in the characterization of oxide NPs in sunscreen sprays, providing consistent information related to NPs and their interactions in the formulations.

DNA-PK/Chk2 induces centrosome amplification during prolonged replication stress.

The antineoplastic drug hydroxyurea (HU), when used at subtoxic doses, induces prolonged replication stress and centrosome amplification. This causes genomic instability and increases the malignancy of the recurring tumor. The mechanism of centrosome amplification induced by prolonged replication stress, however, is still unclear. Here, we examined the involvement of ataxia telangiectasia, mutated (ATM), ataxia telangiectasia, mutated and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK) and found that HU-induced centrosome amplification was inhibited by the depletion of DNA-PKcs, but not ATM and ATR. Inactivation of ATM/ATR in U2OS cells instead caused aneuploidy and cell death. We found DNA-PKcs depletion also abrogated ATM phosphorylation, indicating that ATM activation during prolonged replication stress depends on DNA-PK. Depletion of DNA-PK abrogated checkpoint kinase (Chk)2 activation and partially reduced Chk1 activation. Chk2 depletion blocked HU-induced centrosome amplification, indicating a function of Chk2 in centrosome amplification. We further found that Chk2 was phosphorylated at Thr68 on the mother centriole at late G2 and mitosis when unstressed and on all amplified centrioles induced by HU. In summary, we have elucidated that DNA-PK/Chk2 signaling induces centrosome amplification upon long-term HU treatment, therefore increasing our insight into tumor recurrence after initial chemotherapy.