Rate-controlled rectal drug delivery in man with a hydrogel preparation

Cylindrical hydrogels of hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent were prepared by radical polymerization at 70°C. After washing they were soaked in an aqueous drug solution of antipyrine or theophylline. The in vitro drug release experiments were performed in 100 ml isotonic glucose at 37°C. Rectal administration of a hydrogel preparation containing antipyrine was performed in two subjects for 72 h. With a theophylline-containing hydrogel preparation rectal drug administration was performed in six volunteers for 24 h. Plasma and saliva samples were taken regularly and the in vivo drug release was determined by means of a deconuolution procedure. In vitro 1.12g antipyrine had been released according to a matrix-type profile for 72 h, whereas it was calculated that this was 1.13 and 1.09 g in vivo in the two subjects. The release profile in vivo was very similar to that in vitro. The theophylline hydrogel preparation released in vitro a total of 288 ± 6 mg of drug in 24 h and in vivo this amount was calculated to be 288 ± 11 mg (mean ± s.d.). Near-constant plasma theophylline concentrations were obtained after administering the hydrogel preparation. In all six subjects the cumulative drug profile was in almost perfect agreement with that observed in vitro. Hydrogels offer interesting perspectives as rate-controlled rectal drug delivery systems because of the predictable release profile in vivo on the basis of observations in a simple in vitro model

Rekenprogramma's voor adviseur en veehouder

Wageningen UR Livestock Research heeft rekenprogramma’s voor melkvee (Bedrijfs Begrotingsprogramma Rundvee -BBPR), pluimvee (Bedrijfswijzer Pluimvee) en varkens (Bedrijfswijzer Varkens). Deze programma’s simuleren de bedrijfsvoering van een praktijkbedrijf. Wat je daarmee als adviseur en veehouder kunt, beschrijft dit artike

Vitamin K-Dependent Carboxylase in Skin

Vitamin K-dependent carboxylase is demonstrated in skin microsomes from humans, rats, rabbits, and mice. This enzyme converts a number of distinct protein-bound glutamic acid residues into γ-carboxyglutamic acid residues, which strongly interact with Ca++ ions. The enzymatic activity (expressed per mg protein) in skin is about 20% of that in liver. Vitamin K-dependent carboxylase is present in both epidermal and dermal tissue. It is demonstrated that warfarin treatment in mice results in an accumulation of noncarboxylated precursor proteins in both dermal and epidermal microsomes. Most probably this effect of warfarin is not restricted to mice, but occurs also in the skin of patients under oral anticoagulant therapy. A possible relation between vitamin K-dependent skin carboxylase and the γ-carboxyglutamic acid-containing protein in calcified nodules from patients with scleroderma and dermatomyositis is discussed

Curci-Ferrari mass and the Neuberger problem

We study the massive Curci-Ferrari model as a starting point for defining BRST quantisation for Yang-Mills theory on the lattice. In particular, we elucidate this proposal in light of topological approaches to gauge-fixing and study the case of a simple one-link Abelian model.Comment: 10 pages, uses elsart.cls style file. Eq.(18) corrected for final publicatio

Economie van mais in bedrijfsverband

In dit rapport staan de financiële gevolgen van managementmaatregelen op het gebied van snijmaos. Belangrijke aandachtspunten zijn bemesting, onkruidbestrijding, opbrengst en kwaliteit, mechanisatie en voeding

Source population synthesis and the Galactic diffuse gamma-ray emission

Population synthesis is used to study the contribution from undetected sources to the Galactic ridge emission measured by EGRET. Synthesized source counts are compared with the 3rd EGRET catalogue at low and high latitudes. For pulsar-like populations, 5-10% of the emission >100 MeV comes from sources below the EGRET threshold. A steeper luminosity function can increase this to 20% without violating EGRET source statistics. Less luminous populations can produce much higher values without being detected. Since the unresolved source spectrum is different from the interstellar spectrum, it could provide an explanation of the observed MeV and GeV excesses above the predictions, and we give an explicit example of how this could work.Comment: Astrophysics and Space Science, in press. (Proceedings of Conference 'The multi-messenger approach to high-energy gamma-ray sources', Barcelona, 2006). Minor changes for accepted version, updated reference

Broeikasgasmodule BBPR

De Nederlandse melkveehouderij draagt via de emissies van lachgas en methaan bij aan de emissies van broeikasgassen. De uitbreiding van het BedrijfsBegrotingsProgramma Rundvee (BBPR) met een boeikasgasmodule maakt het mogelijk om de kosteneffectiviteit van emissiereducerende maatregelen in één rekengang te berekenen. De kosteneffectiviteit is het verschil in financieel saldo gedeeld door het verschil in emissie. De emissie van het gemiddelde melkveebedrijf in Nederland bedraagt volgens de berekening met de broeikasgasmodule van BBPR 0.8 kg CO2-equivalenten per kg melk voor bedrijven op minerale grondsoorten en 1.3 kg CO2-equivalenten per kg melk voor bedrijven op veengrond. Het verhogen van het aandeel maïs in het rantsoen verlaagt de emissie slechts vrij gering, maar levert financieel voordeel op. Minder weidegang resulteert in een aanzienlijke emissiereductie, maar is een dure maatregel. Het gebruik van nitraatloze voorjaarsmeststoffen levert slechts een geringe bijdrage aan de emissiereductie. Mestvergisting, volgens het principe van co-vergisting van aangevoerde snijmaïskuil, kan de emissie tot 24% reduceren, maar is voor een gemiddeld bedrijf te duur

Practicalities of using non-local or non-recent multilocus sequence typing data for source attribution in space and time of human campylobacteriosis

In this study, 1208 Campylobacter jejuni and C. coli isolates from humans and 400 isolates from chicken, collected in two separate periods over 12 years in The Netherlands, were typed using multilocus sequence typing (MLST). Statistical evidence was found for a shift of ST frequencies in human isolates over time. The human MLST data were also compared to published data from other countries to determine geographical variation. Because only MLST typed data from chicken, taken from the same time point and spatial location, were available in addition to the human data, MLST datasets for other Campylobacter reservoirs from selected countries were used. The selection was based on the degree of similarity of the human isolates between countries. The main aim of this study was to better understand the consequences of using non-local or non-recent MLST data for attributing domestically acquired human Campylobacter infections to specific sources of origin when applying the asymmetric island model for source attribution. In addition, a power-analysis was done to find the minimum number of source isolates needed to perform source attribution using an asymmetric island model. This study showed that using source data from other countries can have a significant biasing effect on the attribution results so it is important to carefully select data if the available local data lack in quality and/or quantity. Methods aimed at reducing this bias were proposed

Association of polymorphisms in the beta-2 adrenergic receptor gene with fracture risk and bone mineral density

Summary: Signaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms influence receptor function. We show that these polymorphisms are not associated with fracture risk or bone mineral density in the UCP, Rotterdam Study, and GEFOS cohorts. Introduction: Signaling through the beta-2 adrenergic receptor (B2AR) on the osteoblast influences bone remodeling in rodents. In the B2AR gene, three polymorphisms are known to influence receptor function in vitro and in vivo (rs1042713, rs1042714, and rs1800888). We examined the role of these polymorphisms in the B2AR gene on human bone metabolism. Methods: We performed nested case–control studies to determine the association of these polymorphisms with fracture risk in the Utrecht Cardiovascular Pharmacogenetics (UCP) cohort and in three cohorts of the Rotterdam Study. We also determined the association of these polymorphisms with bone mineral density (BMD) in the GEFOS Consortium. UCP contains drug-dispensing histories from community pharmacies linked to national registrations of hospital discharges in the Netherlands. The Rotterdam Study is a prospective cohort study investigating demographics and risk factors of chronic diseases. GEFOS is a large international collaboration studying the genetics of osteoporosis. Fractures were defined by ICD-9 codes 800–829 in the UCP cohort (158 cases and 2617 unmatched controls) and by regular X-ray examinations, general practitioner, and hospital records in the Rotterdam Study (2209 cases and 8559 unmatched controls). BMD was measured at the femoral neck and lumbar spine using dual-energy X-ray absorptiometry in GEFOS (N = 32,961). Results: Meta-analysis of the two nested case–control studies showed pooled odds ratios of 0.98 (0.91–1.05, p = 0.52), 1.04 (0.97–1.12, p = 0.28), and 1.16 (0.83–1.62, p = 0.38) for the associations betwee

Intraperitoneal pharmacokinetics of systemic oxaliplatin, 5-fluorouracil and bevacizumab in patients with colorectal peritoneal metastases

Background: Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population. This study investigates to what extent systemic anti-cancer therapy crosses the peritoneal barrier. Methods: In a Phase I study, eighteen patients received systemic oxaliplatin, 5-FU, and bevacizumab. Plasma and peritoneal fluid samples were collected to measure drug concentrations. A non-compartmental analysis determined the Area Under the Curve (AUC) for oxaliplatin and 5-FU in both matrices. Intraperitoneal (IP) and intravenous (IV) exposure ratios were calculated, along with the bevacizumab concentration IP/IV ratio. The relationship between tumour load and IP/IV ratios and the correlation between the IP/IV ratios of different treatments were assessed statistically. Results: A total of 438 5-FU samples and 578 oxaliplatin samples were analysed in plasma and peritoneal fluid. Bevacizumab was quantified with 17 measurements in plasma and 15 measurements IP. Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A correlation was found between oxaliplatin and bevacizumab IP/IV ratios (R=0.69, p=0.01). No statistical correlations were found between the other investigated drugs. Conclusions: Our findings indicate that only a small percentage of systemically administered anti-cancer treatment reaches the IP cavity, questioning their efficacy against PM. This strengthens the hypothesis for repeated intraperitoneal chemotherapy to reach adequate anti-cancer drug levels.</p