No abstract

No abstract

No abstract

A macromolecular pro-drug of a known anti-viral agent Zidovudine (AZT) was synthesized and evaluated as a sustained drug delivery system. The pro-drug was synthesized by coupling the drug to 2-hydroxyethyl methacrylate (HEMA) through a succinic spacer to get a monomeric drug conjugate which was polymerized to obtain the polymeric pro-drug. The pro-drug was subjected for in-vitro drug release study in buffers of pH 1.2 and 7.4. The hydrolytic stability of the pro-drug to pepsin was assessed in simulated gastric fluid (SGF, pH 1.2) and to α-chymotrypsin in simulated intestinal fluid (SIF, pH 7.4). The results showed that the drug release from the polymeric backbone takes place in a sustained manner over a period of 24 h, and the amount of drug released was comparatively higher at pH 7.4. Plasmatic hydrolysis studies of succinylzidovudine showed nearly complete release of AZT. At all pH conditions in the presence and absence of α-chymotrypsin, AZT was released preferentially in comparison with the succinyl derivative. The in-vivo release studies in rabbits after oral administration of AZT conjugate demonstrated a sustained release of parent drug over a period of 24 h. The pro-drug provided a significant increase in the area under the plasma concentration time curve as compared to free drug and extended the plasma half-life from 1.06 h to 8.08 h. This study suggested that, after oral administration, the drug-polymer conjugate can release AZT for prolonged periods, thus improving the pharmacokinetics of AZT and decreasing the fluctuation in plasma drug levels that can lead to toxicity.

The primary aim of day-care surgery units is to allow for early recovery of the patients so that they can return to their familiar 'home' environment; the management hence should be focused towards achieving these ends. The benefits could include a possible reduction in the risk of thromboembolism and hospital-acquired infections. Furthermore, day-care surgery is believed to reduce the average unit cost of treatment by up to 70% as compared to inpatient surgery. With more than 20% of the world's disease burden, India only has 6% of the world's hospital beds. Hence, there is an immense opportunity for expansion in day-care surgery in India to ensure faster and safer, cost-effective patient turnover. For this to happen, there is a need of change in the mindset of all concerned clinicians, surgeons, anaesthesiologists and even the patients. A group of nine senior consultants from various parts of India, a mix of private and government anaesthesiologists, assembled in Mumbai and deliberated and discussed on the various aspects of day-care surgery. They formulated a consensus statement, the first of its kind in the Indian scenario, which can act as a guidance and tool for day-care anaesthesia in India. The statements are derived from the available published evidence in peer-reviewed literature including guidelines of several bodies such as the American Society of Anesthesiologists, British Association of Day Surgery and International Association of Ambulatory Surgery. The authors also offer interpretive comments wherever such evidence is inadequate or contradictory.

No abstract

In conclusion, concentrating solely in development of drug discovery programs is not enough but it is important to maintain balance between the drug discovery and drug delivery systems that are more specific and effective in targeting CNS of AD patients.

Pim kinases, also known as Serine/Threonine kinases, are intensively studied protein drug targets in cancer research. They play crucial role in the regulation of signal transduction cascades that promote cell survival, proliferation and drug resistance. Pim kinases are overexpressed in several hematopoietic and solid tumors and support in vitro/in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. Pim kinases do not have an identified regulatory domain, as they are constitutively active. They appear to be critical downstream effectors of number of oncoproteins. When overexpressed, they mediate drug resistance to agents such as Rapamycin. X-ray crystallographic studies reveal that unlike other kinases, Pim kinases have a hinge region, which forms a unique binding pocket for ATP, offering a target for a large number of potent small-molecule Pim kinase inhibitors. Combination therapy of Pim kinase inhibitors with chemotherapeutic and other kinase modulators seems to produce an additive cytotoxic effect in cancer cells. Though clinical trials have been carried out on the first Pim inhibitory agent, SGI-1776, no concept data could be generated due to its early withdrawal. However, It has helped in accelerating the discovery of several novel Pim inhibitors in recent years. Current research on Pim kinase is expected to lead to a new generation of potent Pim kinase inhibitors with appropriate pharmacological profiles suitable for human cancer therapy in the near future. Herein, we review the synthetic route and mechanistical studies of Pim kinase inhibitors which are currently in human trials.