PULSATILE RELEASE OF KETOPROFEN FROM COMPRESSION COATED TABLETS USING EUDRAGIT® POLYMERS

Objective: The objective of the present research work is to develop compression coated tablet of ketoprofen as a pulsatile release system for treatment of rheumatoid arthritis.Methods: Core tablets of ketoprofen were prepared using the wet granulation method and evaluated for appearance, hardness, friability, weight variation, thickness, disintegration time and % drug release. Core tablets were coated with Eudragit S100 and Eudragit L100 by compression coating method to achieve desired lag time. The blends of core and coating materials were evaluated for bulk density, tapped density, Hausner's ratio, % Compressibility index and angle of repose. Compression coated tablets were evaluated for appearance, hardness, friability, weight variation, thickness and % drug release.Results: Core tablets, as well as compression coated tablets, showed acceptable Pharmaco technical properties. Optimized core tablets were disintegrated within 15s due to the effectiveness of super disintegrant, sodium starch glycolate. Dissolution studies of compression coated tablets in media with different pH (1.2, 6.8, and 7.4) showed that drug release could be modulated by changing the concentration of EudragitL100 and Eudragit S100. The optimized batch exhibited 80% drug release up to 6 h with a 4 h lag time. Stability study of the optimized formulation indicated no significant change in appearance, physical parameters, drug content and drug release profile at accelerated conditions for two months.Conclusion: compression coated tablet of ketoprofen was successfully developed to achieve burst drug release after specific lag time.Keywords: Chronomodulated drug delivery, Pulsatile release, Compression coated tablets, Lag tim

Is Desmin Propensity to Aggregate Part of its Protective Function?

Desmin is the major protein component of the intermediate filaments (IFs) cytoskeleton in muscle cells, including cardiac. The accumulation of cleaved and misfolded desmin is a cellular hallmark of heart failure (HF). These desmin alterations are reversed by therapy, suggesting a causal role for the IFs in the development of HF. Though IFs are known to play a role in the protection from stress, a mechanistic model of how that occurs is currently lacking. On the other hand, the heart is uniquely suited to study the function of the IFs, due to its inherent, cyclic contraction. That is, HF can be used as a model to address how IFs afford protection from mechanical, and possibly redox, stress. In this review we provide a brief summary of the current views on the function of the IFs, focusing on desmin. We also propose a new model according to which the propensity of desmin to aggregate may have been selected during evolution as a way to dissipate excessive mechanical and possibly redox stress. According to this model, though desmin misfolding may afford protection from acute injury, the sustained or excessive accumulation of desmin aggregates could impair proteostasis and contribute to disease

Accommodation, Pattern Glare, and Coloured Overlays

We manipulated the accommodative response using positive and negative lenses to study any association between symptoms of pattern glare and accommodation. Two groups of eighteen young adults were selected from seventy-eight on the basis (i) that their rate of reading increased by 5% or more with an overlay compared to their rate without it, and (ii) that they reported more than 2 symptoms of pattern glare (group 1) or had no such increment in reading speed and reported fewer than 2 symptoms (group 2). Under double-masked conditions participants observed at 0.4 m a pattern of stripes while measurements of accommodation were made using an open field autorefractor with and without positive and negative trial lenses (0.75 D), and with and without a coloured overlay. Pattern glare was also assessed with and without the trial lenses. Without lenses, the mean accommodative response in group 1 was 1.55 D, a lag of 0.95 D ± 0.24 D relative to the demand. The lag decreased by 0.43 D ( p &lt; 0.0001) when the chosen overlay was used, an effect that was not shown in group 2 even when lag increased with negative trial lenses ( p = 0.13). In both groups, pattern glare scores were reduced by the trial lenses, but were unaffected by the sign of the lenses. This suggests that symptoms of pattern glare are not strongly associated with accommodative response. </jats:p

Maternal understandings of postnatal depression

Paper one is a systematic literature review of qualitative studies examining postnatal depression in immigrant mothers using a metasynthesis approach. This review involved three phases: a systematic literature search of qualitative studies reporting on postnatal depression among immigrant mothers, critical appraisal of the studies from the literature search, and the metasynthesis of these studies. Fifteen studies met the inclusion, exclusion and quality criteria. The synthesis of the studies demonstrated that immigrant mothers are subjected to two overarching factors of migration and cultural influences that interact and give rise to psychosocial understandings of postnatal depression, healthcare barriers and views of potential remedies lying within the psychosocial domain. Mothers use self-help coping strategies in line with this. Social support appears to play an integral and mediating role for these immigrant mothers removed from their sociocultural context.A grounded theory approach was taken in the second paper to explore illness beliefs in mothers with postnatal depression. Eleven participants were interviewed using a semi-structured interview schedule and data was analysed in line with a grounded theory methodology. A theory of illness beliefs in PND was developed encompassing six core categories: 'unmet expectations', 'identifying stressors in their life context', 'conflict over label', 'antidepressants: the lesser of two evils', 'loss of time' and 'uncertain futures.' It was concluded that participants made multiple appraisals of their PND in light of their initial difficulties, following service involvement, their improvements, their consequences and the future. Participants' narratives were conflicting and uncertain with internal struggles evident as mothers were torn between their desire to be good mothers and their perceptions that PND meant that they were not good enough mothers. The final paper is a critical appraisal that outlines my personal journey through a grounded theory methodology in exploring illness beliefs in postnatal depression. This appraisal first discusses why a qualitative design was chosen and more specifically a grounded theory approach. The difficulties attached to using grounded theory are then considered. Finally in keeping with the need for transparency within the methodology, there is a reflective account of the challenges encountered, the knowledge and skills gained throughout the process and how this has been important for my learning and progression towards becoming a qualified Clinical Psychologist.EThOS - Electronic Theses Online ServiceLynne MacRaeGBUnited Kingdo

IL-6 contributes to the suppression of T and NK cell anti-tumor activity in EGFR-mutant NSCLC

View full abstracthttps://openworks.mdanderson.org/leading-edge/1032/thumbnail.jp

A Novel Role for CCL3 (MIP-1α) in Myeloma-induced Bone Disease via Osteocalcin Downregulation and Inhibition of Osteoblast Function

Upregulation of cytokines and chemokines is a frequent finding in multiple myeloma (MM). CCL3 (also known as MIP-1α) is a pro-inflammatory chemokine whose levels in the MM microenvironment correlate with osteolytic lesions and tumor burden. CCL3 and its receptors, CCR1 and CCR5, contribute to the development of bone disease in MM by supporting tumor growth and regulating osteoclast (OC) differentiation. Here, we identify inhibition of osteoblast (OB) function as an additional pathogenic mechanism in CCL3-induced bone disease. MM-derived and exogenous CCL3 represses mineralization and osteocalcin production by primary human bone marrow stromal cells and HS27A cells. Our results suggest that CCL3 effects on OBs are mediated by ERK activation and subsequent downregulation of the osteogenic transcription factor osterix. CCR1 inhibition reduced ERK phosphorylation and restored both osterix and osteocalcin expression in the presence of CCL3. Finally, treating SCID-hu mice with a small molecule CCR1 inhibitor suggests an upregulation of osteocalcin expression along with OC downregulation. Our results show that CCL3, in addition to its known catabolic activity, reduces bone formation by inhibiting OB function and therefore contributes to OB/OC uncoupling in MM

A Paper-Based Test for Screening Newborns for Sickle Cell Disease

The high cost, complexity and reliance on electricity, specialized equipment and supplies associated with conventional diagnostic methods limit the scope and sustainability of newborn screening for sickle cell disease (SCD) in sub-Saharan Africa and other resource-limited areas worldwide. Here we describe the development of a simple, low-cost, rapid, equipment- and electricity-free paper-based test capable of detecting sickle hemoglobin (HbS) in newborn blood samples with a limit of detection of 2% HbS. We validated this newborn paper-based test in a cohort of 159 newborns at an obstetric hospital in Cabinda, Angola. Newborn screening results using the paper-based test were compared to conventional isoelectric focusing (IEF). The test detected the presence of HbS with 81.8% sensitivity and 83.3% specificity, and identified SCD newborns with 100.0% sensitivity and 70.7% specificity. The use of the paper-based test in a two-stage newborn screening process could have excluded about 70% of all newborns from expensive confirmatory testing by IEF, without missing any of the SCD newborns in the studied cohort. This study demonstrates the potential utility of the newborn paper-based test for reducing the overall cost of screening newborns for SCD and thus increasing the practicality of universal newborn SCD screening programs in resource-limited settings

Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis