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The mainstays of Parkinson's disease (PD) treatment remain symptomatic, including initial dopamine replacement and subsequent deep brain stimulation, however, neither of these approaches is neuroprotective. Neurotrophic factors — proteins that activate cell signalling pathways regulating neuronal survival, differentiation, growth and regeneration — represent an alternative for treating dopaminergic neurons in PD but are difficult to administer clinically because they do not pass through the blood-brain barrier. Glial cell line-derived neurotrophic factor (GDNF) has potent neurotrophic effects particularly but not exclusively on dopaminergic neurons; in animal models of PD, it has consistently demonstrated both neuroprotective and neuroregenerative effects when provided continuously, either by means of a viral vector or through continuous infusion either into the cerebral ventricles (ICV) or directly into the denervated putamen. This led to a human PD study in which GDNF was administered by monthly bolus intracerebroventricular injections, however, no clinical benefit resulted, probably because of the limited penetration to the target brain areas, and instead significant side effects occurred. In an open-label study of continuous intraputamenal GDNF infusion in five patients (one unilaterally and four bilaterally), we reported excellent tolerance, few side effects and clinical benefit evident within three months of the commencement of treatment. The clinical improvement was sustained and progressive, and by 24-months patients demonstrated a 57 and 63% improvement in their off-medication motor and activities of daily living UPDRS subscores, respectively, with clear benefit in dyskinesias. The benefit was associated with a significant increase in putamenal 18F-dopa uptake on positron emission tomography (PET), and in one patient coming to autopsy after 43 months of unilateral infusion there was evident increased tyrosine hydroxylase immunopositive nerve fibres in the infused putamen. A second open trial in 10 patients using unilateral intraputamenal GDNF infusions has also demonstrated a greater than 30% bilateral benefit in both on- and off-medication scores at 24 weeks. Based on our 6-month results, a randomized controlled clinical trial was conducted to confirm the open-label results, however, GDNF infusion over 6-months did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F-dopa uptake surrounding the catheter tip. It is possible that technical differences between this trial and the positive open label studies contributed to this negative outcome. [ABSTRACT FROM AUTHOR]

Recombinant protein pharmaceuticals have revolutionized the treatment of a variety of medical ailments, including cancer, autoimmune diseases, and hemostatic disorders. Proteins manufactured with eukaryotic expression systems may be complex and heterogeneous because of posttranslational modifications (PTMs) and differential proteolytic processing. At one time, detailed characterization and definition of the protein structure were difficult, and the manufacturing process defined the product. If process changes were made, clinical trials were required to demonstrate product equivalence prior to regulatory agency acceptance of the product manufactured by the modified process. To adopt new manufacturing processes in a timely manner, the biopharmaceutical industry and regulatory agencies have worked together over the last few years to develop new guidance documents based on knowledge gained from industry experience in the manufacture and clinical testing of protein pharmaceuticals (1,2). Manufacturers of protein pharmaceuticals consistently strive to deliver the highest quality product in a cost-efficient manner. This can be accomplished through optimization of the production process and incorporation of new technologies to enhance product purity and yield. Process improvements may include a change of the host cell line, enhancement of the cell culture medium or cell culture management, or modifications to the purification process. In some cases, an additional manufacturing site is brought online to augment production capacity. [ABSTRACT FROM AUTHOR]

Apoptosis, or programmed cell death (PCD), is a highly organized physiologic event that plays an essential role in controlling cell number in many normal processes, ranging from fetal development to adult tissue homeostasis. The process of apoptosis is tightly regulated by a number of gene products that promote or block cell death at different stages of apoptosis. Abnormal regulation of apoptosis has been implicated in the onset of a wide range of diseases, including cancer. Approaches to resensitize cancer cells to apoptosis represent an important future strategy for cancer treatment, which include restoring lost apoptosis intermediates, inactivating antiapoptotic proteins, triggering apoptosis pathways that remain intact in cancer cells, and inducing apoptosis by targeting specific tumorigenic lesions. This chapter discusses recent advances in this field and highlights novel therapeutic approaches exploiting apoptotic pathways for cancer treatment. [ABSTRACT FROM AUTHOR]

This paper evaluates the performance of some major ICA algorithms like Bell and Sejnowski's infomax algorithm, Cardoso's Joint Approximate Diagonalization of Eigen matrices (JADE) and Comon's algorithm in a biomedical blind source separation problem. Independent signals representing Fetal ECG (FECG) and Maternal ECG (MECG) are generated and then mixed linearly in the presence of white or pink noise to simulate a recording of electrocardiogram. ICA has been used to extract FECG, but very less literature is available on the performance, i.e., how does it behave in clinical environment. So there is a used to evaluate performance of these algorithms in Biomedical. To quantify the performance of ICA algorithms, two scenarios, i.e., (a) different amplitude ratios of simulated maternal and fetal ECG, (b) different values of additive white gaussian noise or pink noise, were investigated. Higher order and Second order performances were measured by performance index and signal-to-error ratio respectively. The selected ICA algorithms separate the white and pink noises equally well. The performance of the Comon's algorithm is slightly less compared to the other two algorithms. [ABSTRACT FROM AUTHOR]