Safety profile of oxcarbazepine: results from a prescription-event monitoring study

Purpose: To monitor safety of oxcarbazepine, prescribed in primary care in England, using prescription-event monitoring (PEM). Methods: Postmarketing surveillance using observational cohort technique of PEM. Exposure data were obtained from dispensed British National Health Service prescriptions issued by general practitioners (GPs) March 2000–July 2003. Demographic, drug utilization, and clinical event data were collected from questionnaires posted to GPs at least 6 months after first prescription date for each patient. Incidence densities (IDs) (number of first reports per 1,000 patient-months of treatment) were calculated and differences for events reported in month 1 (ID1) and months 2–6 (ID2–6) (99% confidence intervals) were examined for changes in event rates. Follow-up and causality assessment of medically significant events were undertaken. Results: The cohort comprised 2,243 patients [mean age 40.4 years; range 2–99 years; standard deviation (SD) 18.8; 46.3% (n = 1,038) male]. Most frequently reported primary indications were epilepsy, convulsion (n = 1,111; 49.5%, n = 209; 9.3%, respectively). GPs recorded 932 reasons for stopping medication in 698 (31.1%) patients; most frequent clinical reason “drowsiness/sedation” (n = 57; 2.5% of cohort). Clinical events (excluding indication) associated with starting treatment (lower 99% CI > 0) included: “drowsiness/sedation” (ID1-ID2–6 = 14.2), “nausea/vomiting” (ID1-ID2–6 = 13.0), and dizziness (ID1-ID2–6 = 11.6). Events followed up and assessed as probably related to oxcarbazepine use included rash (7 of 11) and hyponatremia (15 of 38). Discussion:  There were no serious adverse drug reactions reported during this study. Results of the study should be taken in context with other epidemiologic studies

Cure monitoring of a UV cured epoxy resin using a long period grating Mach- Zehnder interferometer

A cascaded long period grating Mach-Zehnder interferometer is used to monitor the change in refractive index of a UV cured epoxy resin over a cure cycle. Fourier techniques are used to calculate the phase shift and frequency spectral amplitude of the associated fringe pattern during the cure. The results are compared with the refractive index change during cure calculated using a Fresnel reflection based technique

The Broad Spectrum HDAC Inhibitor PCI-24781 Induces Caspase- and ROS-Dependent Apoptosis and is Synergistic with Bortezomib in Lymphoma

We investigated the cytotoxicity and biology of the novel broad-spectrum hydroxamic acid-based histone deacetylase inhibitor (HDACi), PCI-24781. PCI-24781 was studied alone and combined with bortezomib in Hodgkin lymphoma (L428) and non-Hodgkin's lymphoma cell lines (Ramos, HF1, SUDHL4). PCI-24781 induced dose-dependent apoptosis that was associated with prominent G0/G1 arrest, decreased S-phase, increased p21 protein expression, and production of reactive oxygen species (ROS). Furthermore, PCI-24781-induced apoptosis was shown to be ROS- and caspase-dependent. Combined PCI-24781 and bortezomib exposure resulted in strong synergistic apoptosis in all cell lines (combination indices 0.19-0.6). Furthermore, compared to either agent alone, PCI-24781/bortezomib resulted in increased caspase cleavage, mitochondrial depolarization, and histone hyperacetylation. Microarray analyses showed that PCI-24781 alone significantly downregulated several antioxidant genes, proteasome components, and NF-kappaB pathway genes, effects which were enhanced further with bortezomib. RT-PCR confirmed downregulation of NF-kappaB targets NF-kappaB1 (p105), c-Myc, and IkappaB-kinase subunits, while gel-shift showed decreased NF-kappaB DNA-binding activity. Taken together, these results suggest that increased oxidative stress and NF-kappaB inhibition, leading to caspase activation and apoptosis, are likely responsible for the activity of PCI-24781 as well as the observed synergy with bortezomib. These data indicate that PCI-24781 has potential therapeutic value in lymphoma as a single-agent and combined with bortezomib

Tight intra-operative blood pressure control versus standard care for patients undergoing hip fracture repair - Hip Fracture Intervention Study for Prevention of Hypotension (HIP-HOP) trial: study protocol for a randomised controlled trial

Background: Hypotension during anaesthesia for hip fracture surgery is common. Recent data suggest that there is an association between the lowest intra-operative blood pressure and mortality, even when adjusted for co-morbidities. This is consistent with data derived from the wider surgical population, where magnitude and duration of hypotension are associated with mortality and peri-operative complications. However, there are no trial to data to support more aggressive blood pressure control. Methods/design: We are conducting a three-centre, randomised, double-blinded pilot study in three hospitals in the United Kingdom. The sample size will be 75 patients (25 from each centre). Randomisation will be done using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation. Participants will be aged >70 years, cognitively intact (Abbreviated Mental Test Score 7 or greater), able to give informed consent and admitted directly through the emergency department with a fractured neck of the femur requiring operative repair. Patients randomised to tight blood pressure control or avoidance of intra-operative hypotension will receive active treatment as required to maintain both of the following: systolic arterial blood pressure >80% of baseline pre-operative value and mean arterial pressure >75 mmHg throughout. All participants will receive standard hospital care, including spinal or general anaesthesia, at the discretion of the clinical team. The primary outcome is a composite of the presence or absence of defined cardiovascular, renal and delirium morbidity within 7 days of surgery (myocardial injury, stroke, acute kidney injury, delirium). Secondary endpoints will include the defined individual morbidities, mortality, early mobility and discharge to usual residence. Discussion: This is a small-scale pilot study investigating the feasibility of a trial of tight intra-operative blood pressure control in a frail elderly patient group with known high morbidity and mortality. Positive findings will provide the basis for a larger-scale study

Stabilising effect of α-lactalbumin on concentrated infant milk formula emulsions heat treated pre- or post-homogenisation

peer-reviewedProtein type and/or heat treatment pre- or post-homogenisation can affect the physical stability of infant formulations during manufacture. Previous research has described the use of α-lactalbumin addition in infant formulae, but has not demonstrated the effect of heating pre- or post-emulsion formulation during processing. The objective of this study was to evaluate the effect of both of these parameters. Three batches of model 1st-stage infant formula containing differing whey protein ratios (60:40 whey: casein with α-lactalbumin content 12, 30 or 48% of total protein) were prepared. Each batch was split; one half receiving heat treatment pre-homogenisation and the second half homogenised and then heat treated. Emulsion stability was determined by size exclusion chromatography, SDS-PAGE, particle size and viscosity measurements. There was a significant (P < 0.05) reduction in the formation of large soluble aggregates upon increasing α-lac concentration in emulsions heat treated either before or after homogenisation. Heat treatment of formulations post-homogenisation resulted in a higher (P < 0.05) D.v09 within the particle size distribution; increasing α-lactalbumin concentration to 30 or 48% significantly (P < 0.05) reduced the D.v09 within the particle size distribution in these emulsions. The viscosity of concentrates (55 % total solids) containing the 12% α-lactalbumin, heat treated post-homogenisation, was significantly greater (P < 0.05) than the equivalent emulsion heat treated pre-homogenisation; increasing the α-lactalbumin concentration to 30 or 48% significantly (P < 0.05) reduced viscosity. When the α-lactalbumin content was increased to 48% as a percentage of the total protein, heating before or after emulsion formation had no effect on concentrate viscosity. The findings demonstrate the importance of thermal denaturation/aggregation of whey proteins (and in particular, the ratio of α-lactalbumin to β-lactoglobulin) prior to homogenisation of infant formula emulsions

Синтез и свойства силикатов висмута, приготовленных методом механической активации

В настоящей работе были синтезированы серии силикатов висмута методоммеханической активации, а также исследованы их свойства такими методами, как ТГ-ДСК анализ и РФА-спектроскопия. Установлено, что для серии, приготовленной с соотношением реагентов Bi:Si = 2:1 после 800 °С наступает плавление, тогда как для серии с эквиатомным соотношением Bi и Si в исходных реагентах плавления в этом температурном интервале не наблюдается. Показано, что при увеличении температуры прокаливания с 500˚С до 700 °С фаза метасиликата висмута (Bi2SiO5) полностью переходит в ортосиликат висмута (Bi4Si3O12), а доля фазы силленита (Bi12SiO20) увеличивается при увеличении соотношения Bi:Si