Serpiginous choroiditis: a complex pharmacotherapeutic approach

Serpiginous choroiditis is a rare recurrent eye disorder which is characterized by formation of irregularly shaped (serpiginous) lesions involving two layers of the eye surface (the retinal pigment epithelium and the choriocapillaris). It is a rare clinical entity which causes less than 5% of posterior uveitis cases (3.9/1, 00,000 person-years). Diagnosing this rare disorder is a challenge in itself followed by its complex pharmacotherapeutic approach which is seen in the following case report. It will aid in bringing to light the various challenges faced in treatment to open a window for early diagnosis and better treatment regimens while keeping in mind the constant motivation and relaxed mind a patient needs to fight such a rare disease

MULTIPLE UNIT PELLET SYSTEM (MUPS) BASED FAST DISINTEGRATING DELAYED-RELEASE TABLETS FOR PANTOPRAZOLE DELIVERY

Objective: The rationale for the study was to develop multiple unit pellet system (MUPS) of delayed release pantoprazole with desired physical properties and unaltered drug release profile from pellets even after compression into a fast disintegrating tablet.Methods: In the presented study, delayed release pellets of pantoprazole were developed by two methods, i.e. extrusion-spheronization and drug layering techniques, coated using enteric polymer and subsequently compressed in to tablet. In drug layering technique, pantoprazole was loaded on Celphere®102 (microcrystalline cellulose spheres) as well as on Suglet® (sugar spheres) in fluid bed processor. Acid resistant polymer Eudragit ND 30D was subsequently coated on each type of drug loaded pellets. Suitable tableting excipients were prepared such as soft pellets, Ceolus® (fibrous grade of microcrystalline cellulose) granules, Ludipress® (compressible lactose composition), Avicel® PH 200 and different combination of them. Various factors like property of pellets to be compressed, coating level, the composition of tableting excipient and ratio of drug-loaded pellets to tableting excipients were identified and optimized.Results: MUPS with delayed releasing pellets of pantoprazole proved to provide sufficient hardness, rapid disintegration property, and unaltered release profile after compression. Delayed release pantoprazole pellets prepared by drug layering on celphere® 102 followed by coating with Eudragit® NE 30D showed better compressibility to withstand the drug release properties. The combination of Ceolus® granules and Ludipress (in 1:1 ratio) was found to be suitable tableting excipient that helped compression of pellets without rupturing polymeric coat. Pellets to excipients ratio at 1:3 was found optimum.Conclusion: Compaction behaviour of pantoprazole delayed-release pellets without loss of original delayed release profile was achieved by formulating as MUPS based tablet of pantoprazole delayed release pellets using celephere® 102 was developed which was found suitable for desired release profile and physical properties

A pharmacovigilance study in patients of chronic non-infective respiratory diseases attending outpatient department of pulmonary medicine in a tertiary care teaching hospital

Background: Adverse drug reactions (ADR) are the known dangers of any medicinal therapy. They are not only responsible for increasing the mortality and morbidity but also for multiplying the health care expenditure. It is important to monitor the adverse effects of the drugs in the patients on treatment for chronic non-infective respiratory diseases attending OPD of pulmonary medicine in a tertiary care teaching hospitalMethods: The study was single-centric, non-randomized and observational hospital-based study which was carried out for a period of 1 and a half years in JJ Hospital. The patients who were included in the study suffered from either of the 4 diseases-Chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis or interstitial lung diseases (ILD). Data were analyzed by using Microsoft excel sheet. Based on the outcome of modified Hartwig and Siegel severity assessment scale, ADRs were grouped into various severity categories.Results: One hundred and thirty-two number of ADRs were seen in 69 out of 352 patients (19.6 %) of the study population. The occurrence of ADR was found slightly higher in males i.e., 53.62% as compared to females i.e., 46.38%. The patients who were on treatment for ILD showed highest percentage of ADRs i.e., 57.89% which is followed by bronchiectasis (17.39%), COPD (16.17%) and lastly asthma (10.26%). The ADRs belonging to GIT system were highest in number i.e., 80. The most frequently occurring ADR in the study was palpitation which occurred in 14 cases i.e., 20.29%. Out of 132 ADRs observed, 96 i.e., 72.73% belonged to the mild category and 36 ADRs i.e., 27.27% belonged to the moderate category. Not a single severe ADR was found in the study.Conclusions: It was found that 19.6% of the patient population suffered from ADRs, which is a considerable number. It is essential that health care professionals should support ADR monitoring process for the safety of the medicinal product. Proper implementation of ADR monitoring will help to reduce the harmful effects by early detection of drug safety problems in patients, assessing the risk-benefit in an individual and the population, improving the selection, rational use of drugs through the provision of timely warning to healthcare professionals

MULTIPLE UNIT PELLET SYSTEM (MUPS) BASED FAST DISINTEGRATING DELAYED-RELEASE TABLETS FOR PANTOPRAZOLE DELIVERY

Objective: The rationale for the study was to develop multiple unit pellet system (MUPS) of delayed release pantoprazole with desired physical properties and unaltered drug release profile from pellets even after compression into a fast disintegrating tablet.Methods: In the presented study, delayed release pellets of pantoprazole were developed by two methods, i.e. extrusion-spheronization and drug layering techniques, coated using enteric polymer and subsequently compressed in to tablet. In drug layering technique, pantoprazole was loaded on Celphere®102 (microcrystalline cellulose spheres) as well as on Suglet® (sugar spheres) in fluid bed processor. Acid resistant polymer Eudragit ND 30D was subsequently coated on each type of drug loaded pellets. Suitable tableting excipients were prepared such as soft pellets, Ceolus® (fibrous grade of microcrystalline cellulose) granules, Ludipress® (compressible lactose composition), Avicel® PH 200 and different combination of them. Various factors like property of pellets to be compressed, coating level, the composition of tableting excipient and ratio of drug-loaded pellets to tableting excipients were identified and optimized.Results: MUPS with delayed releasing pellets of pantoprazole proved to provide sufficient hardness, rapid disintegration property, and unaltered release profile after compression. Delayed release pantoprazole pellets prepared by drug layering on celphere® 102 followed by coating with Eudragit® NE 30D showed better compressibility to withstand the drug release properties. The combination of Ceolus® granules and Ludipress (in 1:1 ratio) was found to be suitable tableting excipient that helped compression of pellets without rupturing polymeric coat. Pellets to excipients ratio at 1:3 was found optimum.Conclusion: Compaction behaviour of pantoprazole delayed-release pellets without loss of original delayed release profile was achieved by formulating as MUPS based tablet of pantoprazole delayed release pellets using celephere® 102 was developed which was found suitable for desired release profile and physical properties

Inhibition of Rho-kinase differentially affects axon regeneration of peripheral motor and sensory nerves

The small GTPase RhoA and its down-stream effector Rho-kinase (ROCK) are important effector molecules of the neuronal cytoskeleton. Modulation of the RhoA/ROCK pathway has been shown to promote axonal regeneration, however in vitro and animal studies are inconsistent regarding the extent of axonal outgrowth induced by pharmacological inhibition of ROCK. We hypothesized that injury to sensory and motor nerves result in diverse activation levels of RhoA, which may impact the response of those nerve fiber modalities to ROCK inhibition. We therefore examined the effects of Y-27632, a chemical ROCK inhibitor, on the axonal outgrowth of peripheral sensory and motor neurons grown in the presence of growth-inhibiting chondroitin sulfate proteoglycans (CSPGs). In addition we examined the effects of three different doses of Y-27632 on nerve regeneration of motor and sensory nerves in animal models of peripheral nerve crush. In vitro, sensory neurons were less responsive to Y-27632 compared to motor neurons in a non-growth permissive environment. These differences were associated with altered expression and activation of RhoA in sensory and motor axons. In vivo, systemic treatment with high doses of Y-27632 significantly enhanced the regeneration of motor axons over short distances, while the regeneration of sensory fibers remained largely unchanged. Our results support the concept that in a growth non-permissive environment, the regenerative capacity of sensory and motor axons is differentially affected by the RhoA/ROCK pathway, with motor neurons being more responsive compared to sensory. Future treatments, that are aimed to modulate RhoA activity, should consider this functional diversity. (C) 2014 Elsevier Inc. All rights reserved

Clinical management of chronic inflammatory demyelinating polyneuropathy (CIDP) in Europe and India: An exploratory study

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder causing inflammatory demyelination of peripheral nerves and consecutive disability. Diagnostic criteria and treatments are well established, but it is unknown how clinical practice may differ in different geographical regions. In this multicentre study, clinical management of CIDP was compared in 44 patients from Germany, India and Norway regarding diagnostic and therapeutic procedures. All centres used EFNS/PNS diagnostic criteria for CIDP but diagnostic workup varied regarding screening for infectious diseases, genetic testing and nerve biopsy. Intravenous immunoglobulin and prednisolone were the most common therapies in all centres with differences in indication and dosage. Patients from the Indian cohort were the most severely affected with less diverse therapeutic approaches, whereas psychological strain did not differ significantly from the two other cohorts. Our exploratory study discloses an unaddressed issue in management of CIDP that should be further investigated to optimise standard of care for CIDP worldwide

Mapping axon initial segment structure and function by multiplexed proximity biotinylation.

Axon initial segments (AISs) generate action potentials and regulate the polarized distribution of proteins, lipids, and organelles in neurons. While the mechanisms of AIS Na+ and K+ channel clustering are understood, the molecular mechanisms that stabilize the AIS and control neuronal polarity remain obscure. Here, we use proximity biotinylation and mass spectrometry to identify the AIS proteome. We target the biotin-ligase BirA* to the AIS by generating fusion proteins of BirA* with NF186, Ndel1, and Trim46; these chimeras map the molecular organization of AIS intracellular membrane, cytosolic, and microtubule compartments. Our experiments reveal a diverse set of biotinylated proteins not previously reported at the AIS. We show many are located at the AIS, interact with known AIS proteins, and their loss disrupts AIS structure and function. Our results provide conceptual insights and a resource for AIS molecular organization, the mechanisms of AIS stability, and polarized trafficking in neurons