bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells
Authors: Choi Hyun Ju , Lim Do Young , Park Jung Han Yoon
Published: June 2009

Background

3,3'-Diindolylmethane (DIM), an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in bothin vivoandin vitromodels. We have previously determined that DIM (0 – 30 μmol/L) inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells.

Methods

HT-29 cells were cultured with various concentrations of DIM (0 – 30 μmol/L) and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [3H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation andin vitrokinase assays for cyclin-dependent kinase (CDK) and cell division cycle (CDC)2 were conducted.

Results

The percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb) and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21CIP1/WAF1and p27KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1.

Conclusion

Here, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.
A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth
Authors: Mita Hiroaki , Toyota Minoru , Aoki Fumio , Akashi Hirofumi , Maruyama Reo , Sasaki Yasushi , Suzuki Hiromu , Idogawa Masashi , Kashima Lisa , Yanagihara Kazuyoshi , Fujita Masahiro , Hosokawa Masao , Kusano Masanobu , Sabau Sorin Vasile , Tatsumi Haruyuki , Imai Kohzoh , Shinomura Yasuhisa , Tokino Takashi
Published: June 2009

Background

Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations ofKRASare infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells.

Methods

DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors forKRASamplification by quantitative PCR, and investigatedKRASamplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect ofKRASknock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively.

Results

DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains theKRASgene locus. Amplification of theKRASlocus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification).KRASmutations were identified in two of the three cell lines in whichKRASwas amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increasedKRAScopy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-typeKRAS, but not in cells with amplified mutantKRAS. Knock-down ofKRASin gastric cancer cells that carried amplified wild-typeKRASresulted in the inhibition of cell growth and suppression of p44/42 MAP kinase and AKT activity.

Conclusion

Our study highlights the utility of DGS for identification of copy-number alterations. Using DGS, we identifiedKRASas a gene that is amplified in human gastric cancer. We demonstrated that gene amplification likely forms the molecular basis of overactivation of KRAS in gastric cancer. Additional studies using a larger cohort of gastric cancer specimens are required to determine the diagnostic and therapeutic implications ofKRASamplification and overexpression.
Health beliefs about bottled water: a qualitative study
Authors: Ward Lorna A , Cain Owen L , Mullally Ryan A , Holliday Kathryn S , Wernham Aaron GH , Baillie Paul D , Greenfield Sheila M
Published: June 2009

Background

There has been a consistent rise in bottled water consumption over the last decade. Little is known about the health beliefs held by the general public about bottled water as this issue is not addressed by the existing quantitative literature. The purpose of this study was to improve understanding of the public's health beliefs concerning bottled mineral water, and the extent to which these beliefs and other views they hold, influence drinking habits.

Methods

A qualitative study using semi-structured interviews, with 23 users of the Munrow Sports Centre on the University of Birmingham campus.

Results

Health beliefs about bottled water could be classified as general or specific beliefs. Most participants believed that bottled water conferred general health benefits but were unsure as to the nature of these. In terms of specific health beliefs, the idea that the minerals in bottled water conferred a health benefit was the most commonly cited. There were concerns over links between the plastic bottle itself and cancer. Participants believed that bottled water has a detrimental effect on the environment. Convenience, cost and taste were influential factors when making decisions as to whether to buy bottled water; health beliefs were unimportant motivating factors.

Conclusion

The majority of participants believed that bottled water has some health benefits. However, these beliefs played a minor role in determining bottled water consumption and are unlikely to be helpful in explaining recent trends in bottled water consumption if generalised to the UK population. The health beliefs elicited were supported by scientific evidence to varying extents. Most participants did not feel that bottled water conferred significant, if any, health benefits over tap water.
Changes in physical health among participants in a multidisciplinary health programme for long-term unemployed persons
Authors: Schutgens Christine AE , Schuring Merel , Voorham Toon AJ , Burdorf Alex
Published: June 2009

Background

The relationship between poor health and unemployment is well established. Health promotion among unemployed persons may improve their health. The aims of this study were to investigate characteristics of non-participants and drop-outs in a multidisciplinary health promotion programme for long-term unemployed persons with health complaints, to evaluate changes in physical health among participants, and to investigate determinants of improvement in physical health.

Methods

A longitudinal, non-controlled design was used. The programme consisted of two weekly exercise sessions and one weekly cognitive session during 12 weeks. The main outcome measures were body mass index, blood pressure, cardiorespiratory fitness, abdominal muscle strength, and low back and hamstring flexibility. Potential determinants of change in physical health were demographic variables, psychological variables (self-esteem, mastery, and kinesiophobia), and self-perceived health.

Results

The initial response was 73% and 252 persons had complete data collection at baseline. In total, 36 subjects were lost during follow-up. Participants were predominantly low educated, long-term unemployed, and in poor health. Participation in the programme was not influenced by demographic and psychological factors or by self-reported health. Drop-outs were younger and had a lower body mass index at baseline than subjects who completed the programme. At post-test, participants' cardiorespiratory fitness, abdominal muscle strength, and flexibility had increased by 6.8%–51.0%, whereas diastolic and systolic blood pressures had decreased by 2.2%–2.5%. The effect sizes ranges from 0.17–0.68.

Conclusion

Participants with the poorest physical health benefited most from the programme and gender differences in improvement were observed. Physical health of unemployed persons with health complaints improved after participation in this health promotion programme, but not sufficiently, considering their poor physical health at baseline.
Effectiveness of physical training for self-employed persons with musculoskeletal disorders: a randomized controlled trial
Authors: Heinrich Judith , Anema Johannes R , de Vroome Ernest MM , Blatter Birgitte M
Published: June 2009

Background

Despite the fact that the population of self-employed persons is still growing and at risk for long term disability due to a number of risk factors, there is still a lack of information on the effectiveness of interventions for this specific group.

Methods

To determine the effectiveness of physical training without a cognitive behavioral component and workplace specific exercises (PT) and physical training with a cognitive behavioral component and workplace specific exercises (PTCBWE), we conducted a pragmatic Randomized Controlled Trial, stratified into two groups. Self-employed persons with a new work disability claim because of musculoskeletal disorders were randomized to PT (n = 53) or PTCBWE (n = 76), or to a corresponding usual care group (n = 50 and n = 75 respectively). Both types of training consisted of cardiovascular training, strengthening, relaxation and posture exercises and took place two or three times a week, for 1–1.5 hours, during three months, also if someone had already returned to work full-time. The primary outcome measure was claim duration (in days) during 12 months follow-up. Pain severity and functional status were secondary outcome measures. All data were assessed at baseline and at 6 and 12 months follow-up. The data with regard to claim duration were analyzed by survival analysis and Cox regression analysis. Secondary outcome measures were analyzed by means of linear regression analysis.

Results

After 12 months of follow-up there was no difference in claim duration between PT and usual care (Hazard Ratio 0.7; 95%CI, 0.4–1.1; p = 0.12) or PTCBWE and usual care (Hazard Ratio 0.9; 95%CI, 0.6–1.4; p = 0.72). Both types of physical training and usual care improved in pain and functional status over time, but there was only a statistically significant difference in favor of PT on pain improvement at 6 months.

Conclusion

In this study, physical training with and without a cognitive behavioral component and workplace specific exercises for self-employed persons with musculoskeletal disorders was not shown to be effective on claim duration, pain severity and functional status at 12 months follow-up.

Trial registration

Current Controlled Trials ISRCTN67766245.
Effect of 6-months of physical exercise on the nitrate/nitrite levels in hypertensive postmenopausal women
Authors: Zaros Pedro R , Pires Carla EM Romero , Bacci Mauricio , Moraes Camila , Zanesco Angelina
Published: June 2009

Background

Evidences have showed that the incidence of arterial hypertension is greater in postmenopausal women as compared to premenopausal. Physical inactivity has been implicated as a major contributor to weight gain and abdominal obesity in postmenopausal women and the incidence of cardiovascular disease increases dramatically after menopause. Additionally, more women than men die each year of coronary heart disease and are twice as likely as men to die within the first year after a heart attack. A healthy lifestyle has been strongly associated with the regular physical activity and evidences have shown that physically active subjects have more longevity with reduction of morbidity and mortality. Nitric oxide (NO) produced by endothelial cells has been implicated in this beneficial effect with improvement of vascular relaxing and reduction in blood pressure in both laboratory animals and human. Although the effect of exercise training in the human cardiovascular system has been largely studied, the majority of these studies were predominantly conducted in men or young volunteers. Therefore, the aim of this work was to investigate the effects of 6 months of dynamic exercise training (ET) on blood pressure and plasma nitrate/nitrite concentration (NOx-) in hypertensive postmenopausal women.

Methods

Eleven volunteers were submitted to the ET consisting in 3 days a week, each session of 60 minutes during 6 months at moderate intensity (50% of heart rate reserve). Anthropometric parameters, blood pressure, NOx- concentration were measured at initial time and after ET.

Results

A significant reduction in both systolic and diastolic blood pressure values was seen after ET which was accompanied by markedly increase of NOx- levels (basal: 10 ± 0.9; ET: 16 ± 2 μM). Total cholesterol was significantly reduced (basal: 220 ± 38 and ET: 178 ± 22 mg/dl), whereas triglycerides levels were not modified after ET (basal: 141 ± 89 and ET: 147 ± 8 mg/dl).

Conclusion

Our study shows that changing in lifestyle promotes reduction of arterial pressure which was accompanied by increase in nitrite/nitrate concentration. Therefore, 6-months of exercise training are an important approach in management arterial hypertension and play a protective effect in postmenopausal women.
Plasmodium falciparum genotypes diversity in symptomatic malaria of children living in an urban and a rural setting in Burkina Faso
Authors: Soulama Issiaka , Nébié Issa , Ouédraogo Alphonse , Gansane Adama , Diarra Amidou , Tiono Alfred B , Bougouma Edith C , Konaté Amadou T , Kabré Gustave B , Taylor Walter RJ , Sirima Sodiomon B
Published: June 2009

Background

The clinical presentation of malaria, considered as the result of a complex interaction between parasite and human genetics, is described to be different between rural and urban areas. The analysis of the Plasmodium falciparum genetic diversity in children with uncomplicated malaria, living in these two different areas, may help to understand the effect of urbanization on the distribution of P. falciparum genotypes.

Methods

Isolates collected from 75 and 89 children with uncomplicated malaria infection living in a rural and an urban area of Burkina Faso, respectively, were analysed by a nested PCR amplification of msp1 and msp2 genes to compare P. falciparum diversity.

Results

The K1 allelic family was widespread in children living in the two sites, compared to other msp1 allelic families (frequency >90%). The MAD 20 allelic family of msp1 was more prevalent (p = 0.0001) in the urban (85.3%) than the rural area (63.2%). In the urban area, the 3D7 alleles of msp2 were more prevalent compared to FC27 alleles, with a high frequency for the 3D7 300bp allele (>30%). The multiplicity of infection was in the range of one to six in the urban area and of one to seven in the rural area. There was no difference in the frequency of multiple infections (p = 0.6): 96.0% (95% C.I: 91.6–100) in urban versus 93.1% (95%C.I: 87.6–98.6) in rural areas. The complexity of infection increased with age [p = 0.04 (rural area), p = 0.06 (urban area)].

Conclusion

Urban-rural area differences were observed in some allelic families (MAD20, FC27, 3D7), suggesting a probable impact of urbanization on genetic variability of P. falciparum. This should be taken into account in the implementation of malaria control measures.
Protein Never in Mitosis Gene A Interacting-1 regulates calpain activity and the degradation of cyclooxygenase-2 in endothelial cells
Authors: Liu Tongzheng , Schneider Ryan A , Shah Vaibhav , Huang Yongcheng , Likhotvorik Rostislav I , Keshvara Lakhu , Hoyt Dale G
Published: June 2009

Background

The peptidyl-proline isomerase, Protein Never in Mitosis Gene A Interacting-1 (PIN1), regulates turnover of inducible nitric oxide synthase (iNOS) in murine aortic endothelial cells (MAEC) stimulated with E. coli endotoxin (LPS) and interferon-γ (IFN). Degradation of iNOS was reduced by a calpain inhibitor, suggesting that PIN1 may affect induction of other calpain-sensitive inflammatory proteins, such as cyclooxygenase (COX)-2, in MAEC.

Methods

MAEC, transduced with lentivirus encoding an inactive control short hairpin (sh) RNA or one targeting PIN1 that reduced PIN1 by 85%, were used. Cells were treated with LPS/IFN, calpain inhibitors (carbobenzoxy-valinyl-phenylalaninal (zVF), PD150606), cycloheximide and COX inhibitors to determine the effect of PIN1 depletion on COX-2 and calpain.

Results

LPS or IFN alone did not induce COX-2. However, treatment with 10 μg LPS plus 20 ng IFN per ml induced COX-2 protein 10-fold in Control shRNA MAEC. Induction was significantly greater (47-fold) in PIN1 shRNA cells. COX-2-dependent prostaglandin E2 production increased 3-fold in KD MAEC, but did not increase in Control cells. The additional increase in COX-2 protein due to PIN1 depletion was post-transcriptional, as induction of COX-2 mRNA by LPS/IFN was the same in cells containing or lacking PIN1. Instead, the loss of COX-2 protein, after treatment with cycloheximide to block protein synthesis, was reduced in cells lacking PIN1 in comparison with Control cells, indicating that degradation of the enzyme was reduced. zVF and PD150606 each enhanced the induction of COX-2 by LPS/IFN. zVF also slowed the loss of COX-2 after treatment with cycloheximide, and COX-2 was degraded by exogenous μ-calpain in vitro. In contrast to iNOS, physical interaction between COX-2 and PIN1 was not detected, suggesting that effects of PIN1 on calpain, rather than COX-2 itself, affect COX-2 degradation. While cathepsin activity was unaltered, depletion of PIN1 reduced calpain activity by 55% in comparison with Control shRNA cells.

Conclusion

PIN1 reduced calpain activity and slowed the degradation of COX-2 in MAEC, an effect recapitulated by an inhibitor of calpain. Given the sensitivity of COX-2 and iNOS to calpain, PIN1 may normally limit induction of these and other calpain substrates by maintaining calpain activity in endothelial cells.
Conflicting priorities: evaluation of an intervention to improve nurse-parent relationships on a Tanzanian paediatric ward
Authors: Manongi Rachel N , Nasuwa Fortunata R , Mwangi Rose , Reyburn Hugh , Poulsen Anja , Chandler Clare IR
Published: June 2009

Background

Patient, or parent/guardian, satisfaction with health care provision is important to health outcomes. Poor relationships with health workers, particularly with nursing staff, have been reported to reduce satisfaction with care in Africa. Participatory research approaches such as the Health Workers for Change initiative have been successful in improving provider-client relationships in various developing country settings, but have not yet been reported in the complex environment of hospital wards. We evaluated the HWC approach for improving the relationship between nurses and parents on a paediatric ward in a busy regional hospital in Tanzania.

Methods

The intervention consisted of six workshops, attended by 29 of 31 trained nurses and nurse attendants working on the paediatric ward. Parental satisfaction with nursing care was measured with 288 parents before and six weeks after the workshops, by means of an adapted Picker questionnaire. Two focus-group discussions were held with the workshop participants six months after the intervention.

Results

During the workshops, nurses demonstrated awareness of poor relationships between themselves and mothers. To tackle this, they proposed measures including weekly meetings to solve problems, maintain respect and increase cooperation, and representation to administrative forces to request better working conditions such as equipment, salaries and staff numbers. The results of the parent satisfaction questionnaire showed some improvement in responsiveness of nurses to client needs, but overall the mean percentage of parents reporting each of 20 problems was not statistically significantly different after the intervention, compared to before it (38.9% versus 41.2%). Post-workshop focus-group discussions with nursing staff suggested that nurses felt more empathic towards mothers and perceived an improvement in the relationship, but that this was hindered by persisting problems in their working environment, including poor relationships with other staff and a lack of response from hospital administration to their needs.

Conclusion

The intended outcome of the intervention was not met. The priorities of the intervention – to improve nurse-parent relationships – did not match the priorities of the nursing staff. Development of awareness and empathy was not enough to provide care that was satisfactory to clients in the context of working conditions that were unsatisfactory to nurses.
Anti-tumor effects of a human VEGFR-2-based DNA vaccine in mouse models
Authors: Xie Ke , Bai Rui-Zhen , Wu Yang , Liu Quan , Liu Kang , Wei Yu-Quan
Published: June 2009

Background

Vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2 (Flk-1/KDR), play a key role in tumor angiogenesis. Blocking the VEGF-VEGFR-2 pathway may inhibit tumor growth. Here, we used human VEGFR-2 as a model antigen to explore the feasibility of immunotherapy with a plasmid DNA vaccine based on a xenogeneic homologue of this receptor.

Methods

The protective effects and therapeutic anti-tumor immunity mediated by the DNA vaccine were investigated in mouse models. Anti-angiogenesis effects were detected by immunohistochemical staining and the alginate-encapsulate tumor cell assay. The mechanism of action of the DNA vaccine was primarily explored by detection of auto-antibodies and CTL activity.

Results

The DNA vaccine elicited a strong, protective and therapeutic anti-tumor immunity through an anti-angiogenesis mechanism in mouse models, mediated by the stimulation of an antigen-specific response against mFlk-1.

Conclusion

Our study shows that a DNA vaccine based on a xenogeneic homologue plasmid DNA induced autoimmunity against VEGFR-2, resulting in inhibition of tumor growth. Such vaccines may be clinically relevant for cancer immunotherapy.
Identifying alemtuzumab as an anti-myeloid cell antiangiogenic therapy for the treatment of ovarian cancer
Authors: Pulaski Heather L , Spahlinger Gregory , Silva Ines A , McLean Karen , Kueck Angela S , Reynolds R Kevin , Coukos George , Conejo-Garcia Jose R , Buckanovich Ronald J
Published: June 2009

Background

Murine studies suggest that myeloid cells such as vascular leukocytes (VLC) and Tie2+ monocytes play a critical role in tumor angiogenesis and vasculogenesis. Myeloid cells are a primary cause of resistance to anti-VEGF therapy. The elimination of these cells from the tumor microenvironment significantly restricts tumor growth in both spontaneous and xenograft murine tumor models. Thus animal studies indicate that myeloid cells are potential therapeutic targets for solid tumor therapy. Abundant VLC and Tie2+ monocytes have been reported in human cancer. Unfortunately, the importance of VLC in human cancer growth remains untested as there are no confirmed therapeutics to target human VLC.

Methods

We used FACS to analyze VLC in ovarian and non-ovarian tumors, and characterize the relationship of VLC and Tie2-monocytes. We performed qRT-PCR and FACS on human VLC to assess the expression of the CD52 antigen, the target of the immunotherapeutic Alemtuzumab. We assessed Alemtuzumab's ability to induce complement-mediated VLC killing in vitro and in human tumor ascites. Finally we assessed the impact of anti-CD52 immuno-toxin therapy on murine ovarian tumor growth.

Results

Human VLC are present in ovarian and non-ovarian tumors. The majority of VLC appear to be Tie2+ monocytes. VLC and Tie2+ monocytes express high levels of CD52, the target of the immunotherapeutic Alemtuzumab. Alemtuzumab potently induces complement-mediated lysis of VLC in vitro and ex-vivo in ovarian tumor ascites. Anti-CD52 immunotherapy targeting VLC restricts tumor angiogenesis and growth in murine ovarian cancer.

Conclusion

These studies confirm VLC/myeloid cells as therapeutic targets in ovarian cancer. Our data provide critical pre-clinical evidence supporting the use of Alemtuzumab in clinical trials to test its efficacy as an anti-myeloid cell antiangiogenic therapeutic in ovarian cancer. The identification of an FDA approved anti-VLC agent with a history of clinical use will allow immediate proof-of-principle clinical trials in patients with ovarian cancer.
Ethnicity and OPRM Variant Independently Predict Pain Perception and Patient-Controlled Analgesia Usage for Post-Operative Pain
Authors: Tan Ene-choo , Lim Eileen CP , Teo Yik-ying , Lim Yvonne , Law Hai-yang , Sia Alex T
Published: June 2009

Background

Morphine consumption can vary widely between individuals even for identical surgical procedures. As mu-opioid receptor (OPRM1) is known to modulate pain perception and mediate the analgesic effects of opioid compounds in the central nervous system, we examined the influence of two OPRM polymorphisms on acute post-operative pain and morphine usage in women undergoing elective caesarean delivery.

Results

Data on self-reported pain scores and amount of total morphine use according to patient-controlled analgesia were collected from 994 women from the three main ethnic groups in Singapore. We found statistically significant association of the OPRM 118A>G with self-administered morphine during the first 24-hour postoperative period both in terms of total morphine (p = 1.7 × 10−5) and weight-adjusted morphine (p = 6.6 × 10−5). There was also significant association of this OPRM variant and time-averaged self-rated pain scores (p = 0.024). OPRM 118G homozygotes used more morphine and reported higher pain scores than 118A carriers. Other factors which influenced pain score and morphine usage include ethnicity, age and paying class.

Conclusion

Our results suggest that ethnicity and OPRM 118A>G genotype are independent and significant contributors to variation in pain perception and postoperative morphine use in patients undergoing cesarean delivery.
Human rights of persons with mental illness in Indonesia: more than legislation is needed
Authors: Irmansyah I , Prasetyo YA , Minas H
Published: June 2009

Background

Although attention to human rights in Indonesia has been improving over the past decade, the human rights situation of persons with mental disorders is still far from satisfactory. The purpose of this paper is to examine the legal framework for protection of human rights of persons with mental disorder and the extent to which Indonesia's international obligations concerning the right to health are being met.

Methods

We examined the Indonesian constitution, Indonesian laws relevant to the right to health, the structure and operation of the National Human Rights Commission, and what is known about violations of the human rights of persons with mental illness from research and the media.

Results

The focus of the Indonesian Constitution on rights pre-dated the Universal Declaration, Indonesia has ratified relevant international covenants and domestic law provides an adequate legal framework for human rights protections. However, human rights abuses persist, are widespread, and go essentially unremarked and unchallenged. The National Human Rights Commission has only recently become engaged in the issue of protection of the rights of persons with mental illness.

Conclusion

More than legislation is needed to protect the human rights of persons with mental illness. Improving the human rights situation for persons with mental illness in Indonesia will require action by governments at national, provincial and district levels, substantial increases in the level of investment in mental health services, coordinated action by mental health professionals and consumer and carer organisations, and a central role for the National Human Rights Commission in protecting the rights of persons with mental illness.
Antimicrobial activities of commercial nanoparticles against an environmental soil microbe, Pseudomonas putida KT2440
Authors: Gajjar Priyanka , Pettee Brian , Britt David W , Huang Wenjie , Johnson William P , Anderson Anne J
Published: June 2009

Background

The release of heavy metal-containing nanoparticles (NP) into the environment may be harmful to the efficacy of beneficial microbes that function in element cycling, pollutant degradation and plant growth. Nanoparticles of Ag, CuO and ZnO are of interest as antimicrobials against pathogenic bacteria. We demonstrate here their antimicrobial activity against the beneficial soil microbe, Pseudomonas putida KT2440.

Results

Toxicity was detected in a KT2440 construct possessing a plasmid bearing the luxAB reporter genes. "As manufactured" preparations of nano- Ag, -CuO and -ZnO caused rapid dose-dependent loss of light output in the biosensor. Cell death accompanied loss in Lux activity with treatments by nano-Ag and -CuO, but with -ZnO the treatments were bacteriostatic rather than bactericidal. Bulk equivalents of these products showed no inhibitory activity, indicating that particle size was determinant in activity. Flow Field-Flow Fractionation (FlFFF) of an aqueous suspension of the nano-CuO and ZnO revealed a small proportion of 5 nm NP and aggregated particulates with sizes ranging between 70 nm and 300 nm; the majority portion of material was aggregated into particles larger than 300 nm in size. Thus within the commercial preparation there may be microbially active and inactive forms.

Conclusion

The "as-made" NP of Ag, CuO and ZnO have toxic effects on a beneficial soil microbe, leading to bactericidal or bacteriostatic effects depending on the NP employed. The lack of toxicity from bulk materials suggests that aggregation of the NP into larger particles, possibly by factors present in the environment may reduce their nontarget antimicrobial activity.
Collagen fleece-bound fibrin sealant is not associated with an increased risk of thromboembolic events or major bleeding after its use for haemostasis in surgery: a prospective multicentre surveillance study
Authors: Birth Mathias , Figueras Joan , Bernardini Stéphane , Troen Tine , Günther Klaus , Mirza Darius , Mortensen Frank Viborg
Published: June 2009

Background

Topical haemostatic agents are used to help achieve haemostasis during surgery when standard surgical techniques are insufficient. The objective of this study was to confirm the safety profile of an equine collagen patch coated with human fibrinogen and human thrombin with particular focus on the occurrence of thromboembolic events (TEEs), major bleeding and immunological events.

Methods

This was a non-interventional, multicentre, prospective, surveillance study in which a collagen fleece-bound fibrin sealant was prescribed in accordance with its marketing authorisation. The decision to use the sealant was based solely on current surgical practice. All patients that received the sealant and provided informed consent were included. TEEs (any coagula-based occlusion in a vessel or the heart identified by symptomatic clinical signs and/or verified by paraclinical examination), major bleeding (any bleeding that required intervention), and immunological events (hypersensitivity including anaphylaxis) that occurred during surgery, post-operative hospital stay or 6 months of follow-up were reported as adverse events. The primary endpoint was the proportion of patients experiencing a confirmed TEE.

Results

A total of 3098 patients were recruited at 227 centres in 12 European countries. The most frequent types of surgery were hepatic (33%), gastrointestinal (16%) and urological (14%) and the main indication for surgery was for primary (35%) or secondary (20%) malignancy. Forty-six patients (1.5%, 95% CI 1.1–2.0%) had at least one TEE during the study. The most commonly reported TEEs were pulmonary embolism or post-procedural pulmonary embolism (n = 18) and deep vein thrombosis (n = 9). There were 64 major bleedings in 62 patients and 9 immunological events in 8 patients.

Conclusion

Collagen fleece-bound fibrin sealant does not appear to be associated with an increased risk of TEEs, major bleeding or immunological events in patients undergoing surgery.

Trial registration

Clinicaltrials.gov number: NCT00285623
Maternal epileptic seizure induced by Pentylenetetrazol: Apoptotic neurodegeneration and decreased GABAB1 receptor expression in prenatal rat brain
Authors: Naseer Muhammad Imran , Shupeng Li , Kim Myeong Ok
Published: June 2009

Epilepsy is a prominent sign of neurological dysfunction in children with various fetal and maternal deficiencies. However, the detailed mechanism and influences underlying epileptic disorders are still unrevealed. The hippocampal neurons are vulnerable to epilepsy-induced pathologic changes and often manifests as neuronal death. The present study was designed to investigate the effect of maternal epileptic seizure on apoptotic neuronal death, modulation of GABAB1receptor (R), and protein kinase A-α (PKA) in prenatal rat hippocampal neurons at gestational days (GD) 17.5. Seizure was induced in pregnant rat using intraperitoneal injection of pentylenetetrazol (PTZ) (40 mg/kg for 15 days). To confirm the seizure electroencephalography (EEG) data was obtained by the Laxtha EEG-monitoring device in the EEG recording room and EEG were monitored 5 min and 15 min after PTZ injection. The RT-PCR and Western blot results showed significant increased expression of cytochrome-c and caspases-3, while decreased levels of GABAB1R, and PKA protein expression upon ethanol, PTZ and ethanol plus PTZ exposure in primary neuronal cells cultured from PTZ-induced seizure model as compare to non-PTZ treated maternal group. Apoptotic neurodegeneration was further confirmed with Fluoro-Jade B and propidium iodide staining, where neurons were scattered and shrunken, with markedly condensed nuclei in PTZ treated group compared with control. This study for the first time indicate that PTZ-induced seizures triggered activation of caspases-3 to induce widespread apoptotic neuronal death and decreased GABAB1R expression in hippocampal neurons, providing a possible mechanistic link between maternal epilepsy induced neurodegeneration alteration of GABAB1R and PKA expression level during prenatal brain development. This revealed new aspects of PTZ and ethanol's modulation on GABAB1R, learning and memory. Further, explain the possibility that children delivered by epileptic mothers may have higher risk of developmental disturbances and malformations.
Incidence of breast cancer in Italy: mastectomies and quadrantectomies performed between 2000 and 2005
Authors: Piscitelli Prisco , Santoriello Antonio , Buonaguro Franco M , Di Maio Massimo , Iolascon Giovanni , Gimigliano Francesca , Marinelli Alessandra , Distante Alessandro , Serravezza Giuseppe , Sordi Emiliano , Cagossi Katia , Artioli Fabrizio , Santangelo Michele , Fucito Alfredo , Gimigliano Raffaele , Brandi Maria Luisa , Crespi Massimo , Giordano Antonio ,   the CROM and the Human Health Foundation study group
Published: June 2009

Objectives

We aimed to determine the incidence of women's breast cancer in Italy without using statistical approximations.

Methods

We analyzed the national hospitalizations database at the Ministry of Health to calculate the number of major surgeries in Italian women (mastectomies and quadrantectomies) due to breast cancer between 2000 and 2005, overall and by age groups (<44, 45–64, 65–74 and ≥ 75 years old).

Results

Over the six years examined, an overall number of 100,745 mastectomies and 168,147 quadrantectomies were performed. A total of 41,608 major surgeries due to breast cancer were performed in the year 2000 and this number rose to 47,200 in 2005, with a 13.4% increase over six years.

Conclusion

by analyzing the hospitalizations database concerning major breast surgery, incidence of breast cancer in Italy was found to be 26.5% higher than the official estimations which have been computed using statistical models (namely 47,200 vs. 37,300 cases in year 2005).
Disease association with two Helicobacter pylori duplicate outer membrane protein genes, homB and homA
Authors: Oleastro Monica , Cordeiro Rita , Yamaoka Yoshio , Queiroz Dulciene , Mégraud Francis , Monteiro Lurdes , Ménard Armelle
Published: June 2009

Background

homB encodes a Helicobacter pylori outer membrane protein. This gene was previously associated with peptic ulcer disease (PUD) and was shown to induce activation of interleukin-8 secretion in vitro, as well as contributing to bacterial adherence. Its 90%-similar gene, homA, was previously correlated with gastritis. The present study aimed to evaluate the gastric disease association with homB and homA, as well as with the H. pylori virulence factors cagA, babA and vacA, in 415 H. pylori strains isolated from patients from East Asian and Western countries. The correlation among these genotypes was also evaluated.

Results

Both homB and homA genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains. In Western strains (n = 234, 124 PUD and 110 non-ulcer dyspepsia (NUD), homB, cagA and vacA s1 were all significantly associated with PUD (p = 0.025, p = 0.014, p = 0.039, respectively), and homA was closely correlated with NUD (p = 0.072). In East Asian strains (n = 138, 73 PUD and 65 NUD), homB was found more frequently than homA, and none of these genes was associated with the clinical outcome.

Overall, homB was associated with the presence of cagA (p = 0.043) and vacA s1 (p < 0.001), whereas homA was found more frequently in cagA-negative (p = 0.062) and vacA s2 (p < 0.001) strains.

Polymorphisms in homB and homA copy number were observed, with a clear geographical specificity, suggesting an involvement of these genes in host adaptation. A correlation between the homB two-copy genotype and PUD was also observed, emphasizing the role of homB in the virulence of the strain.

Conclusion

The global results suggest that homB and homA contribute to the determination of clinical outcome.
Antiphospholipid antibody profiles in lupus nephritis with glomerular microthrombosis: a prospective study of 124 cases
Authors: Zheng Hui , Chen Yi , Ao Wen , Shen Yan , Chen Xiao-wei , Dai Min , Wang Xiao-dong , Yan Yu-cheng , Yang Cheng-de
Published: June 2009

Introduction

Glomerular microthrombosis (GMT) is a common vascular change in patients with lupus nephritis (LN). The mechanism underlying GMT is largely unknown. Although several studies have reported the association of antiphospholipid antibodies (aPL) with GMT, the relation between GMT and aPL remains controversial. Previous studies have demonstrated that some aPL could bind to several hemostatic and fibrinolytic proteases that share homologous enzymatic domains. Of the protease-reactive aPL, some can inhibit the anticoagulant activity of activated protein C and the fibrinolytic function of plasmin, and hinder the antithrombin inactivation of thrombin. The purpose of this study was to investigate the prevalence of GMT in LN patients and examine the relation between the aPL profiles (including some protease-reactive aPL) and GMT.

Methods

Renal biopsy specimens were examined for the presence of glomerular microthrombi. Plasma samples from 25 LN patients with GMT (LN-GMT group) and 99 LN patients without GMT (LN-non-GMT group) were tested for lupus anticoagulant and antibodies against cardiolipin, β2 glycoprotein I, plasmin, thrombin, tissue plasminogen activator, and annexin II.

Results

The prevalence of GMT in LN patients was 20.2%. Compared with the LN-non-GMT group, the LN-GMT group had an elevated systemic lupus erythematosus disease activity index; elevated renal tissue injury activity and chronicity indices; elevated serum creatinine, blood urea nitrogen, and proteinuria levels; a lower serum C3 level and much intense glomerular C3, C1q staining; and a higher frequency of hypertension (P < 0.05 for all). Additionally, the detection rate of lupus anticoagulant, immunoglobulin G (IgG) anti-β2 glycoprotein I and anti-thrombin antibodies were higher in the LN-GMT group than in the LN-non-GMT group (P < 0.05 for all). No statistical differences were found in the detection rates of IgG anti-cardiolipin, plasmin, tissue plasminogen activator, or annexin II antibodies (P > 0.05 for all). No detectable difference in IgM autoantibodies to the above antigens was observed between the two groups.

Conclusions

GMT occurs in approximately 20.2% of LN patients. Patients with GMT have severer renal tissue injuries and poorer renal functions than patients without GMT. The lupus anticoagulant and antibodies against β2 glycoprotein I and thrombin may play a role in GMT.
The utility of MRI in predicting radiographic erosions in the metatarsophalangeal joints of the rheumatoid foot: a prospective longitudinal cohort study
Authors: Mundwiler Matthew L , Maranian Paul , Brown Douglas H , Silverman Jeffrey M , Wallace Daniel , Khanna Dinesh , Louie James , Furst Daniel E , Weisman Michael H
Published: June 2009

Introduction

Magnetic resonance imaging (MRI) may reveal rheumatoid arthritis (RA) changes in the feet when hands are normal. The purpose of this study was to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a metatarsophalangeal (MTP) erosion on MRI to predict a subsequent radiographic erosion in the same joint. Similar analyses were performed for bone marrow edema, predicting a subsequent MRI erosion. Descriptive results of other lesions are reported.

Methods

Fifty patients with RA of less than 5 years' duration who were rheumatoid factor-positive and/or anti-cyclic citrullinated peptide-positive were recruited. Patients on anti-tumor necrosis factor (TNF) therapy were excluded. Anti-TNF therapy could begin after enrollment. MRI and radiographs of the 3rd, 4th, and 5th MTP joints bilaterally were taken at baseline and at 6, 12, and 24 months. Clinical data were collected.

Results

Fifty patients were recruited; 46 patients had suitable data. Results for MRI erosions predicting subsequent radiographic erosions for 6, 12, and 24 months, respectively, were as follows: sensitivity 0.75, 0.60, 0.75; specificity 0.93, 0.94, 0.94; PPV 0.086, 0.10, 0.17; NPV 0.998, 0.995, 0.995. Results for MRI bone marrow edema predicting MRI erosions at 6 and 12 months, respectively, revealed sensitivity 0.50, 0.67; specificity 0.97, 0.97; PPV 0.25, 0.50; NPV 0.99, 0.99. Synovitis was the most common finding and, when present in isolation, resolved on 67.3% of subsequent studies. MRI erosions persisted on subsequent studies with one exception. Forty-six percent of the cohort was on anti-TNF therapy after study inception.

Conclusions

The PPV of MRI erosions to predict subsequent radiographic erosions was low. Similarly, the PPV of bone marrow edema to predict a later MRI erosion was low. Alternatively, the NPV of the absence of an MRI erosion or bone marrow edema predicts that a later radiographic erosion or MRI erosion will likely not develop. Anti-TNF therapies may have resulted in the lower-than-anticipated PPVs. MRI descriptions of bone edema may represent a more critical time to treat in order to avoid damage, whereas an MRI erosion represents more permanent damage. This study suggests that imaging modalities more sensitive than radiographs are necessary to monitor disease in the biologic era.
Degradome expression profiling in human articular cartilage
Authors: Swingler Tracey E , Waters Jasmine G , Davidson Rosemary K , Pennington Caroline J , Puente Xose S , Darrah Clare , Cooper Adele , Donell Simon T , Guile Geoffrey R , Wang Wenjia , Clark Ian M
Published: June 2009

Introduction

The molecular mechanisms underlying cartilage destruction in osteoarthritis are poorly understood. Proteolysis is a key feature in the turnover and degradation of cartilage extracellular matrix where the focus of research has been on the metzincin family of metalloproteinases. However, there is strong evidence to indicate important roles for other catalytic classes of proteases, with both extracellular and intracellular activities. The aim of this study was to profile the expression of the majority of protease genes in all catalytic classes in normal human cartilage and that from patients with osteoarthritis (OA) using a quantitative method.

Methods

Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur (NOF). Total RNA was purified, and expression of genes assayed using Taqman® low-density array quantitative RT-PCR.

Results

A total of 538 protease genes were profiled, of which 431 were expressed in cartilage. A total of 179 genes were differentially expressed in OA versus NOF cartilage: eight aspartic proteases, 44 cysteine proteases, 76 metalloproteases, 46 serine proteases and five threonine proteases. Wilcoxon ranking as well as the LogitBoost-NR machine learning approach were used to assign significance to each gene, with the most highly ranked genes broadly similar using each method.

Conclusions

This study is the most complete quantitative analysis of protease gene expression in cartilage to date. The data help give direction to future research on the specific function(s) of individual proteases or protease families in cartilage and may help to refine anti-proteolytic strategies in OA.