Co-treatment with riluzole and GDNF is necessary for functional recovery after ventral root avulsion injury

Unilateral avulsion of lumbar ventral roots kills approximately 50% of injured motoneurons within 2 weeks of surgery. Immediate treatment involving surgical reimplantation of the ventral root (VRI) or intrathecal glial cell line-derived neurotrophic factor (GDNF) delivery or intraperitoneal injection of riluzole for 2 weeks ameliorates motoneuron death to 80% of control but combining the different treatment paradigms did not further enhance survival except when GDNF was combined with VRI. At 3 months, all combined treatments provided a neuroprotective effect compared to avulsion only, but the neuroprotective effect of surgical reimplantation alone was not maintained unless combined with riluzole and GDNF treatment. Analysis of regenerating motoneurons using retrograde labelling techniques showed that riluzole, but not GDNF, increased the number of dendrites per labelled motoneuron. However, when functional motor recovery was assessed using the BBB locomotor score and rotarod tests, only VRI animals treated with riluzole and GDNF application showed significantly improved locomotor function in both tests. Our results show that functional recovery appears related to a combination of enhanced dendrite formation, increased motoneuron survival and the neurotrophic actions of GDNF. Thus, combination treatment may offer a new therapeutic strategy for treating patients with avulsion injury.     

Development and validation of an HPLC method for AG331 bulk drug substance and lyophilized powder for injection

AG331 is a water soluble glucuronate salt of a novel antitumor compound synthesized by protein structure based drug design. A lyophilized powder for injection was developed for clinical studies. During HPLC assay development, AG331 showed an inherent tailing problem due to an amino group in the structure. An optimized reverse-phase gradient HPLC method was developed to minimize the tailing and separate AG331 from its synthetic intermediates (I-1, I-2, I-3, I-4, I-5, I-6, I-8), other impurities and degradation compounds. The method was shown to be linear, precise, accurate, rugged and stability-indicating.     

The impact of visual impairment on functional vision of children in rural South India: the Kariapatti Pediatric Eye Evaluation Project

PURPOSE: To determine the impact of visual impairment on functional vision of children in a rural population of south India. METHODS: A visual function questionnaire (LVP-VFQ) was administered to 1194 children aged 7 to 15 years identified through a systematic random sampling technique from 144 hamlets of Kariapatti in rural south India as part of a larger population-based project. Visual acuity estimations and clinical examinations for morbidity were performed in these 1194 children. A Rasch analysis was performed to validate the use of the instrument in this population. Bootstrap estimates (95% confidence intervals) of the regression coefficients were used to compare visual function scores between children with normal sight and children with uncorrected monocular and binocular visual impairment. RESULTS: The mean age of children was 10.3 +/- 2.1 years. The reliability estimates were 0.82 for person ability and 0.88 for item difficulty parameters, according to the Rasch analysis. A separation index of 2.15 was obtained for person measures and 2.74 for item measures, and the mean square infit and outfit statistics were 1.03 (Z(STD) 0.1) and 0.99 (Z(STD) -0.1), respectively. Children with monocular visual impairment (bootstrap estimate [95%CI] -0.05 [-0.08 to -0.01]) and binocular visual impairment (bootstrap estimate [95%CI] -0.09 [-0.11 to -0.07]) were more likely to have functional visual deficits than were normally sighted peers. CONCLUSIONS: Monocular or binocular visual impairment impacts on the functional vision of children in this rural population. Further studies are needed to determine the impact of treatment of visual impairment on functional vision in children of this population.     

Characterization of poly(D,L-lactic-co-glycolic acid) based nanoparticulate system for enhanced delivery of antigens to dendritic cells

Biodegradable nanoparticles made of poly(D,L-lactic acid-co-glycolic acid) (PLGA) copolymer were characterized for enhanced delivery of antigens to murine bone marrow derived dendritic cells (DCs) in vitro. PLGA nanoparticles were efficiently phagocytosed by the DCs (CD11c+, MHC class II+, CD86+) in culture, resulting in their intracellular localization. The efficiency of the uptake was influenced by the incubation time and nanoparticle concentration. DCs pulsed with PLGA nanoparticles containing an immunomodulator, monophosphoryl lipid A (MPLA), showed upregulation of surface expression of MHC class II and CD86 molecules. Delivery of a cancer-associated antigen (MUC1 mucin peptide: BLP25) and MPLA in PLGA nanoparticles was shown to be superior to their delivery in the soluble form for activation of na?ve T cells of normal and MUC1-transgenic mice. These results strongly suggest that PLGA nanoparticles provide an efficient vaccine delivery system for targeting DCs and the development of DC based cellular vaccines.     

Tracheobronchial foreign bodies

Ojective : Foreign body inhalation is an extremely serious problem in children and sometimes result in sudden death. The current mortality rate from foreign body inhalation is between 0% and 1.8% according to various studies. In spite of this, undiagnosed and unsuspected foreign bodies still occur in the airway.dMethods : Pediatric patients with documented foreign body inhalation, treated in the Department of Pediatrics, Bapuji Hospital, JJM Medical College during 1997-2000 are included in the analysis. Children with or without positive history of aspiration were examined and the diagnosis was made on the basis of history, clinical findings, radilogic evaluation and strong index of suspicion in those children where reasonable appropriate treatment failed to resolve the respiratory symptoms. Bronchoscopy was performed for a suspected foreign body on 165 children.Result : A review of 165 pediatric cases of suspected foreign body aspiration revealed, children between 1 and 3 years were found to be very vulnerable for aspiration. Majority of children were boys. Over 70% of the patients had positive history of inhalation. Only 60% of the patients presented immediately, that is within 24 hours after aspiration. Common symptoms were cough and respiratory distress. Physical examination showed abnormal finding in 91% of cases. Decreased air entry was the significant clinical sign. Obstructive emphysema was found in majority of the cases (49.5%). Rigid bronchoscopy under general anaesthesia was the preferred method for removal of aspirated foreign body. In 65 (61.9%) cases foreign body was lodged in the right main bronchus and majority of these were organic in nature, that is 96(91.43%).Conclusion : Tracheobronchial foreign bodies should be strongly suspected in pediatric age group who present with a suggestive history, even when physical and radiographie evidence is absent. The modalities of diagnosis, management and outcome are discussed.     

Electronic visual prosthesis

Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are incurable diseases that result in profound vision loss due to degeneration of the light sensing photoreceptors. However, the discovery that direct electrical stimulation of the retinal neurons creates visual sensation has inspired prosthetic devices aimed to restore useful vision in RP/AMD patients. The approach to one such electronic visual prosthesis is described in this article. The prosthesis consists of an external unit and an internal unit. The communication link has three components--power and data transfer from the external to the internal unit, and data transfer from the internal to the external unit. A novel method of integrating power transfer and back telemetry is described here. The goal is to design a stimulator chip with a small area with low power consumption. This chip, capable of stimulating 60 dedicated electrodes, is fabricated using AMI 1.2 microm process technology and the results are presented. Improvements in the design to increase the number of outputs to 1,000 have been discussed. The new circuit is aimed at increasing the circuit density, reducing power per stimulus, and meeting the requirements more closely than the previous designs. The results of the designed chip are presented.