131 research outputs found

    Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: Experimental animal study

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    <p>Abstract</p> <p>Background</p> <p>Alkali injury is one of the most devastating injuries to the eye. It results in permanent unilateral or bilateral visual impairment. Chemical eye injury is accompanied by an increase in the oxidative stress. Anti-inflammatory and antioxidant agents play a major role in the treatment of chemical eye injuries. The purpose of this study is to evaluate the anti-inflammatory (clinical and histopathological) and antioxidant effects of Tualang honey versus conventional treatment in alkali injury on the eyes of rabbits.</p> <p>Methods</p> <p>A preliminary study was carried out prior to the actual study to establish the alkali chemical injury on rabbit's cornea and we found that alkali chemical injury with 2 N NaOH showed severe clinical inflammatory features. In actual study, alkali injury with 2 N NaOH was induced in the right eye of 10 New Zealand White rabbits' cornea. The rabbits were divided into two groups, Group A was given conventional treatment and Group B was treated with both topical and oral Tualang honey. Clinical inflammatory features of the right eye were recorded at 12 hours, 24 hours, 72 hours, 5<sup>th </sup>day and 7<sup>th </sup>day post induction of alkali burn on the cornea. The histopathological inflammatory features of the right corneas of all rabbits were also evaluated on day-7. The level of total antioxidant status and lipid peroxidation products in the aqueous humour, vitreous humour and serum at day-7 were estimated biochemically. Fisher's Exact, Chi-Square and Mann-Whitney test were used to analyse the data.</p> <p>Results</p> <p>There was no statistically significant difference in clinical inflammatory features (p > 0.05) between honey treated and the conventional treated group at different times of examination. Histopathological examination of the cornea showed the number of polymorphonuclear leucocytes was below 50 for both groups (mild grade). There was also no significant difference in the level of total antioxidant status as well as lipid peroxidation products in aqueous humour (p = 0.117, p = 0.382 respectively), vitreous humour (p = 0.917, p = 0.248 respectively) and serum (p = 0.917, p = 0.332 respectively) between honey treated and the conventional treated group.</p> <p>Conclusion</p> <p>Tualang honey has almost the equal effects when compared with the conventional treatment in treating alkali injury on rabbit's eye. Future research with more number of rabbits and control group is warranted to explore the anti-inflammatory and antioxidant effects of Tualang honey.</p

    Pharmacokinetics and pharmacodynamics of medication in asphyxiated newborns during controlled hypothermia. The PharmaCool multicenter study

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    <p>Abstract</p> <p>Background</p> <p>In the Netherlands, perinatal asphyxia (severe perinatal oxygen shortage) necessitating newborn resuscitation occurs in at least 200 of the 180–185.000 newly born infants per year. International randomized controlled trials have demonstrated an improved neurological outcome with therapeutic hypothermia. During hypothermia neonates receive sedative, analgesic, anti-epileptic and antibiotic drugs. So far little information is available how the pharmacokinetics (PK) and pharmacodynamics (PD) of these drugs are influenced by post resuscitation multi organ failure and the metabolic effects of the cooling treatment itself. As a result, evidence based dosing guidelines are lacking. This multicenter observational cohort study was designed to answer the question how hypothermia influences the distribution, metabolism and elimination of commonly used drugs in neonatal intensive care.</p> <p>Methods/Design</p> <p>Multicenter cohort study. All term neonates treated with hypothermia for Hypoxic Ischemic Encephalopathy (HIE) resulting from perinatal asphyxia in all ten Dutch Neonatal Intensive Care Units (NICUs) will be eligible for this study. During hypothermia and rewarming blood samples will be taken from indwelling catheters to investigate blood concentrations of several antibiotics, analgesics, sedatives and anti-epileptic drugs. For each individual drug the population PK will be characterized using Nonlinear Mixed Effects Modelling (NONMEM). It will be investigated how clearance and volume of distribution are influenced by hypothermia also taking maturation of neonate into account. Similarly, integrated PK-PD models will be developed relating the time course of drug concentration to pharmacodynamic parameters such as successful seizure treatment; pain assessment and infection clearance.</p> <p>Discussion</p> <p>On basis of the derived population PK-PD models dosing guidelines will be developed for the application of drugs during neonatal hypothermia treatment. The results of this study will lead to an evidence based drug treatment of hypothermic neonatal patients. Results will be published in a national web based evidence based paediatric formulary, peer reviewed journals and international paediatric drug references.</p> <p>Trial registration</p> <p>NTR2529.</p

    Implementing the chronic care model for frail older adults in the Netherlands: study protocol of ACT (frail older adults: care in transition)

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    <p>Abstract</p> <p>Background</p> <p>Care for older adults is facing a number of challenges: health problems are not consistently identified at a timely stage, older adults report a lack of autonomy in their care process, and care systems are often confronted with the need for better coordination between health care professionals. We aim to address these challenges by introducing the geriatric care model, based on the chronic care model, and to evaluate its effects on the quality of life of community-dwelling frail older adults.</p> <p>Methods/design</p> <p>In a 2-year stepped-wedge cluster randomised clinical trial with 6-monthly measurements, the chronic care model will be compared with usual care. The trial will be carried out among 35 primary care practices in two regions in the Netherlands. Per region, practices will be randomly allocated to four allocation arms designating the starting point of the intervention. <it>Participants</it>: 1200 community-dwelling older adults aged 65 or over and their primary informal caregivers. Primary care physicians will identify frail individuals based on a composite definition of frailty and a polypharmacy criterion. Final inclusion criterion: scoring 3 or more on a disability case-finding tool. <it>Intervention</it>: Every 6 months patients will receive a geriatric in-home assessment by a practice nurse, followed by a tailored care plan. Expert teams will manage and train practice nurses. Patients with complex care needs will be reviewed in interdisciplinary consultations. <it>Evaluation</it>: We will perform an effect evaluation, an economic evaluation, and a process evaluation. Primary outcome is quality of life as measured with the Short Form-12 questionnaire. Effect analyses will be based on the “intention-to-treat” principle, using multilevel regression analysis. Cost measurements will be administered continually during the study period. A cost-effectiveness analysis and cost-utility analysis will be conducted comparing mean total costs to functional status, care needs and QALYs. We will investigate the level of implementation, barriers and facilitators to successful implementation and the extent to which the intervention manages to achieve the transition necessary to overcome challenges in elderly care.</p> <p>Discussion</p> <p>This is one of the first studies assessing the effectiveness, cost-effectiveness and implementation process of the chronic care model for frail community-dwelling older adults.</p> <p>Trial registration</p> <p>The Netherlands National Trial Register NTR2160.</p

    Tyrosine kinase signalling in breast cancer: Tyrosine kinase-mediated signal transduction in transgenic mouse models of human breast cancer

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    The ability of growth factors and their cognate receptors to induce mammary epithelial proliferation and differentiation is dependent on their ability to activate a number of specific signal transduction pathways. Aberrant expression of specific receptor tyrosine kinases (RTKs) has been implicated in the genesis of a significant proportion of sporadic human breast cancers. Indeed, mammary epithelial expression of activated RTKs such as ErbB2/neu in transgenic mice has resulted in the efficient induction of metastatic mammary tumours. Although it is clear from these studies that activation these growth factor receptor signalling cascades are directly involved in mammary tumour progression, the precise interaction of each of these signalling pathways in mammary tumourigenesis and metastasis remains to be elucidated. The present review focuses on the role of several specific signalling pathways that have been implicated as important components in RTK-mediated signal transduction. In particular, it focuses on two well characterized transgenic breast cancer models that carry the polyomavirus middle T(PyV mT) and neu oncogenes

    Bioavailability of Iron, Zinc, Phytate and Phytase Activity during Soaking and Germination of White Sorghum Varieties

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    The changes in phytate, phytase activity and in vitro bioavailability of iron and zinc during soaking and germination of three white sorghum varieties (Sorghum bicolor L. Moench), named Dorado, Shandweel-6, and Giza-15 were investigated. Sorghum varieties were soaked for 20 h and germinated for 72 h after soaking for 20 h to reduce phytate content and increase iron and zinc in vitro bioavailability. The results revealed that iron and zinc content was significantly reduced from 28.16 to 32.16% and 13.78 to 26.69% for soaking treatment and 38.43 to 39.18% and 21.80 to 31.27% for germination treatments, respectively. Phytate content was significantly reduced from 23.59 to 32.40% for soaking treatment and 24.92 to 35.27% for germination treatments, respectively. Phytase enzymes will be activated during drying in equal form in all varieties. The results proved that the main distinct point is the change of phytase activity as well as specific activity during different treatment which showed no significant differences between the varieties used. The in vitro bioavailability of iron and zinc were significantly improved as a result of soaking and germination treatments

    Patients' experiences of living with and receiving treatment for fibromyalgia syndrome: a qualitative study

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    <p>Abstract</p> <p>Background</p> <p>Fibromyalgia syndrome (FMS) presents a challenge for patients and health care staff across many medical specialities. The aetiology is multi-dimensional, involving somatic, psychological and social factors. Patients' views were obtained to understand their experience of living with this long-term condition, using qualitative interviews.</p> <p>Methods</p> <p>12 patients were recruited and stratified by age, gender and ethnicity from one rheumatology outpatient clinic, and a departmental held database of patients diagnosed with FMS.</p> <p>Results</p> <p>Patients' accounts of their experience of FMS resonated well with two central concepts: social identity and illness intrusiveness. These suggested three themes for the analytical framework: life before and after diagnosis (e.g. lack of information about FMS, invisibility of FMS); change in health identity (e.g. mental distress, impact on social life) and perceived quality of care (e.g. lack of contact with nurses, attitudes of specialists). The information provided from one male participant did not differ from the female patients, but black and ethnic community patients expressed a degree of suspicion towards the medication prescribed, and the attitudes displayed by some doctors, a finding that has not been previously reported amongst this patient group. Patients expected more consultation time and effective treatment than they received. Subjective experiences and objective physical and emotional changes were non-overlapping. Patients' accounts revealed that their physical, mental and social health was compromised, at times overwhelming and affected their identity.</p> <p>Conclusion</p> <p>FMS is a condition that intrudes upon many aspects of patients' lives and is little understood. At the same time, it is a syndrome that evokes uneasiness in health care staff (as current diagnostic criteria are not well supported by objective markers of physiological or biochemical nature, and indeed because of doubt about the existence of the condition) and places great demands on resources in clinical practice. Greater attention needs to be paid to the links between the explanatory models of patients and staff, and most important, to the interrelationship between the complex physical, psychological and social needs of patients with FMS. Taking a less medical but more holistic approach when drawing up new diagnostic criteria for FMS might match better individuals' somatic and psycho-social symptom profile and may result in more effective treatment.</p

    RAD51B in Familial Breast Cancer.

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    Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk
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