Translational pharmacokinetics and pharmacodynamics of monoclonal antibodies

Monoclonal antibodies (mAbs) are an important therapeutic class with complex pharmacology and interdependent pharmacokinetic (PK) and pharmacodynamics (PD) properties. Understanding the PK and PD of mAbs and their biological and mechanistic underpinnings are crucial in enabling their design and selection, designing appropriate efficacy and toxicity studies, translating PK/PD parameters to humans, and optimizing dose and regimen to maximize success in the clinic. Significant progress has been made in this field however many critical questions still remain. This article gives a brief overview of the PK and PD of mAbs, factors that influence them, and areas of ongoing inquiry. Current tools and translational approaches to predict the PK/PD of mAbs in humans are also discussed

PROTECTIVE ROLE OF DAIDZEIN AGAINST CYCLOPHOSPHAMIDE INDUCED NEPHROTOXICITY IN EXPERIMENTAL RATS

Objective: To evaluate the protective effect of daidzein on cyclophosphamide (CPA) induced nephrotoxicity in experimental rats.Methods: The Wistar rats of either sex were randomly divided into five equal groups: Group I (normal saline 1 ml p. o.), Group II (CPA 150 mg/mg i. p), Group III (Daidzein 20 mg/kg p. o.+CPA 150 mg/kg, i. p.), Group IV (Daidzein 40 mg/kg p. o.+CPA 150 mg/kg, i. p.) and Group V (Daidzein 40 mg/kg p. o., alone). Rats of all groups except Group I and Group V treated with CPA in a dosage of 150 mg/mg i. p in the last five days of treatment. Blood samples were collected on 11th day from each rat and subjected for the evaluation of serum markers such as Serum creatinin, serum urea and serum uric acid. Kidney of each rat was excised and subjected for antioxidant parameters evaluation such as malonyl dialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase and histopathological study.Results: Daidzein explored a significant (P<0.001) role in CPA-induced nephrotoxicity by suppressing serum creatinine, serum urea and serum uric acid. Daidzein also demonstrated significant (P<0.001) protection against CPA-induced nephrotoxicity by decreasing MDA level and by elevating the GSH, SOD, catalase at different doses.Conclusions: The obtained results of present study revealed that daidzein attenuates the CPA-induced nephrotoxicity by antioxidant defence action in rats

Chromate uptake characteristics of the pristine layered double hydroxides of Mg with Al

The layered double hydroxides (LDHs) of Mg with Al readily scavenge dissolved chromate ions under a wide range of conditions. While the chromate uptake is quantitative in the LDH containing 33 mol% Al, the uptake is only 58% of the stoichiometric value in the LDH containing 25 mol% Al. This indicates that the lower symmetry of the NO3− ions in the LDH with 33 mol% Al facilitates the intercalation of chromate ions even under conditions of equilibration with excess dissolved nitrate ions. The chromate uptake obeys the Langmuir adsorption isotherm suggesting that the entire interlayer region of the LDH behaves like a surface. This surface is structural rather than morphological as the chromate uptake correlates negatively with the BET surface area of the LDHs

Behçet's pulmonary artery aneurysms treated with infliximab and monitored with the 6-min walk test

Pulmonary involvement in Behçet's disease (BD) is uncommon; however, it is potentially fatal due to the risk of massive haemoptysis. We describe the case of a 36-year-old male presenting with a 2-month history of worsening dyspnoea, weight loss, haemoptysis, oral ulceration, erythema nodosum and superficial thrombophlebitis. He was diagnosed with pulmonary vasculitis secondary to BD; however, his symptoms were refractory to initial treatment with cyclophosphamide, azathioprine and prednisolone. We therefore trialled infliximab alongside methotrexate, which led to a remarkable improvement in his condition, enabling eventual discontinuation of prednisolone. Whilst not being one of the treatments currently recommended for managing pulmonary involvement in BD, infliximab has previously been successfully used in cases refractory to conventional therapy. We used the 6-min walk test (distance covered and lowest oxygen saturations) to monitor his progress, which correlated with his symptoms. This may represent a useful adjunct in monitoring the activity of pulmonary vasculitis

Imaging the dust sublimation front of a circumbinary disk

We present the first near-IR milli-arcsecond-scale image of a post-AGB binary that is surrounded by hot circumbinary dust. A very rich interferometric data set in six spectral channels was acquired of IRAS08544-4431 with the new RAPID camera on the PIONIER beam combiner at the Very Large Telescope Interferometer (VLTI). A broadband image in the \textit{H} band was reconstructed by combining the data of all spectral channels using the SPARCO method. We spatially separate all the building blocks of the IRAS08544-4431 system in our milliarcsecond-resolution image. Our dissection reveals a dust sublimation front that is strikingly similar to that expected in early-stage protoplanetary disks, as well as an unexpected flux signal of $\sim$4\% from the secondary star. The energy output from this companion indicates the presence of a compact circum-companion accretion disk, which is likely the origin of the fast outflow detected in H$\alpha$. Our image provides the most detailed view into the heart of a dusty circumstellar disk to date. Our results demonstrate that binary evolution processes and circumstellar disk evolution can be studied in detail in space and over time.Comment: PR @ http://www.eso.org/public/news/eso1608

Micorwave Energy Aided Mineral Comminution

Mineral liberation during beneficiation is essentially through comminution. However, the fact that the major slice (up to 50 percent) in the pie for total energy requirements during beneficiation is occupied by comminution, dictates us to look into various possi-bilities to render comminution more energy-efficient. In the early 1900s, efforts for reduction in the crushing and grinding energies based on the concept, 'thermally assisted liberation' (T A L) were made but could not be commercially exploited. With the advent of microwave energy and applications in different commercial operat-ions based on its property of heat generation in materials encouraged it in utilizing as an aid during comminution. Microwave energy heats individual phases in an ore matrix to different heat levels as per individual microwave absorption characteristics. Exposure to microwave energy over discrete time intervals prior to comminution results in development of micro fractures due to differential heating. Weakening of interspatial bonding in the ore matrix helps in lesser energy requirements. Numerous studies on microwave energy applications in the field of mineral processing and extractive metallurgy are under-taken in many parts of the world in recent years

Explicit MBR All-Symbol Locality Codes

Node failures are inevitable in distributed storage systems (DSS). To enable efficient repair when faced with such failures, two main techniques are known: Regenerating codes, i.e., codes that minimize the total repair bandwidth; and codes with locality, which minimize the number of nodes participating in the repair process. This paper focuses on regenerating codes with locality, using pre-coding based on Gabidulin codes, and presents constructions that utilize minimum bandwidth regenerating (MBR) local codes. The constructions achieve maximum resilience (i.e., optimal minimum distance) and have maximum capacity (i.e., maximum rate). Finally, the same pre-coding mechanism can be combined with a subclass of fractional-repetition codes to enable maximum resilience and repair-by-transfer simultaneously