Design and characterization of biodegradable macroporous hybrid inorganic-organic polymer for orthopedic applications.

We have engineered hybrid polymer products based on a hybrid inorganic-organic comacromer consisting of hydroxyapatite (HA), carboxyl terminated polypropylene fumarate (CTPPF), PEG300 and ascorbic acid (AA) as a bone graft material. The integration and the spatial distribution of HA in the polymer backbone were facilitated by silanisation and 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) coupling technique. These comacromers and crosslinked polymer products were characterized by Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM) and Raman mapping techniques. SEM and EDAX analysis substantiate high invitro bioactivity of the polymer products. SEM studies depict a distinct macroporous structure with pore size of 50 to 300µm. These crosslinked hybrid products demonstrated no significant difference in compressive moduli after 4weeks immersion in SBF. In particular, the compressive moduli were found to be comparable with that of trabecular bone. We suggest that the formation of an apatite layer on the surface of the composites deter initial degradation leading to better mechanical stability. As expected, the polymer products displayed negligible degradation in SBF during the first 4weeks which increased to a maximum of 25% by the end of the 8weeks time period. In addition these crosslinked products which are hydrophilic exhibit favorable albumin adsorption, cell viability, HOS cell adhesion and exemplary compatibility. Cumulatively, the results deduced in the present study suggest that these hybrid products have potential as a bone graft material.

Europium Doped Calcium Deficient Hydroxyapatite as Theranostic Nanoplatforms: Effect of Structure and Aspect Ratio.

We present the development of theranostic nanoplatforms (NPs) based on a europium (Eu3+) doped calcium deficient hydroxyapatite (CDHA) core functionalized with cyclodextrin (ß-CD) and cucurbitural (CB[7]). The composition, crystalline structure, aspect ratio, surface area, morphology, and luminescence property of the NPs were investigated by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray analysis (EDAX), the Brunauer-Emmett-Teller (BET) method, transmission electron microscopy (TEM), and fluorescence spectroscopy. The perceivable effects of Eu3+ doping appear in the minor peak shift to larger angles attributed to lower crystallite size and smaller aspect ratios coupled with greater structural strain in the rod shaped theranostic NPs and a shift in their zeta potential toward less negative values. Cell parameter calculations suggest that the doping of Eu3+ would cause the a-axis parameter to decrease slightly as the ionic radius of Eu3+ is smaller than that of Ca2+. Moreover drug release profiles employing 5-fluorouracil (5FU) suggest that these luminescent NPs depict controlled and sustained release profiles. Further the emissive intensities of the NPs in the carrier systems increase with cumulative released amounts of 5FU, suggesting that release of the drug can be monitored by changes in luminescent intensity. In addition, native NPs manifest commendable cytocompatibility as demonstrated by MTT and live/dead protocols, whereas the 5FU loaded NPs demonstrated over 80% HeLa cell death, signifying their therapeutic potential. We envision that these NPs can serve as effective and practical multifunctional probes for theranostic applications.

Cytogenetics of neuroblastoma: a study using fine needle aspiration cultures.

Neuroblastoma is associated with chromosomal aberrations of 1p and 1q in a majority of cases. Some nonrandom secondary changes were observed in this study. The role of these changes in the development and progression of neuroblastoma is examined. Chromosomal analysis was performed on 33 children with neuroblastoma using fine needle aspiration cultures. Metaphases were observed in 57.5% of cases. 86.6% showed the involvement of chromosome 1. Double minutes and unidentifiable markers was also observed. The most frequent secondary changes included add(4)(q35), add(11)(p13), add(14)(q32), add(16)(q12). add(17)(p13), add(19)(q12) and add(21)(q22). Minority of cases showed deletions and translocations. Ploidy pattern ranged from diploid to hypotetraploid. The present study substantiates aberration of chromosome 1 in the form of deletions, additions, duplications and iso-chromosome with some notable secondary abnormalities.

Cytogenetic characterization of Ewing tumors using fine needle aspiration samples. a 10-year experience and review of the literature.

Chromosomal analysis was performed in fine needle aspiration samples of 98 primary Ewing tumors (ETs) prior to treatment. Among the 58 (59.18%) successful cultures, t(11;22)(q24;q12) was observed in 87.9% and 6.8% had abnormalities other than t(11;22), viz., del(22)(q12), der(16)t(1;16)(q12;q11), and variant t(8;22)(q24;q12). Involvement of breakpoints 1q21, 1q22, 3p14, 16q22, and 17p13 was also observed. Numerical abnormalities such as trisomies 8 and 12 were found in 29.3% and 20.6% and trisomy 18 in 17.2%. An attempt was made to evaluate the role of these additional changes in the process of tumor development, metastasis, and progression of the disease. This is the largest cytogenetic study on ET from a single center using a simple and reliable technique of fine-needle aspiration culture. The literature on cytogenetics of ET is reviewed.

Centronuclear myopathy--morphological relation to developing human skeletal muscle: a clinicopathological evaluation.

Centronuclear myopathy (CNM), an uncommon condition, is one of the congenital myopathies. It is believed to arise as a result of maturational arrest, with persistence of myotubes postnatally. However, denervation being the basic disease process and its possible influence on central nervous system causing defect in nuclear migration has also been postulated. Keeping in view these existing controversies, we have studied 17 cases of CNM (neonatal - 1, childhood - 13, adulthood - 3) during the last twelve and a half years. Diagnosis was based on histological and enzyme histochemical findings of muscle biopsy along with clinical data. Ultrastructural characterstics of muscle have been studied in 10 cases. The affected muscle fibres showed a central nucleus (40-99%) with perinuclear halo. Type I fibre predominance with hypoplasia was consistently seen. Fibre type disproportion was noticed in 7 cases. The neonatal form revealed dense oxidative enzyme reaction product in the centre. The morphological features of CNM were compared with foetal skeletal muscles obtained at gestational ages ranging from 9 weeks - 36 weeks (n = 18). In the severe neonatal form th myofibres resembled the foetal myotubes. In the less severe childhood and adult form of CNM, aberrant organization of cytoskeletal network might have played a pathogenetic role in causing the disease.

Neurofilament phosphorylation is increased in ventral horn neurons of neonatal rat spinal cord exposed to cerebrospinal fluid from patients with amyotrophic lateral sclerosis.

Aberrant neurofilament (NF) phosphorylation in the soma of the ventral horn neurons of neonatal rat spinal cord is observed following exposure to cerebrospinal fluid (CSF) of patients suffering from Amyotrophic Lateral Sclerosis (ALS). CSF samples from ALS and non-ALS neurological patients were injected into the spinal subarachnoid space of 3 day old rat pups. After 48 h, sections of spinal cords were stained for the presence of phosphorylated NF epitopes with SMI-31 antibody. The number of neuronal soma staining with this antibody in the ventral and dorsal horns sides of the spinal cord was counted. There was a significant 3-fold increase in the number of soma stained with SMI-31 antibody in the ventral horns of rat spinal cords exposed to CSF of patients with ALS compared to cords from rats exposed to CSF of non-ALS patients and those which were not exposed to any CSF samples. Such an increase in staining of neuronal soma was not observed in the dorsal horns. Hyperphosphorylation of neuronal soma suggests an initial stage of degenerative changes occurring in the motor (ventral horn) neurons following exposure to circulating factor(s) in the CSF of patients with ALS.

Cognitive functioning in patients with complex absence following treatment with sodium valproate.

The association of sodium valproate with cognitive functions was studied in 29 patients with complex absence seizures. Seventeen patients were on monotherapy and twelve on polypharmacy with sodium valproate. Cognitive functions assessed were attention, speech, visuo-speciat perception, memory and intelligence. Behavioral disturbances were also assessed. Two assessments were made six months apart; in the first assessment, attention and speech were adequate, while memory, visuo-spatial perception, and behavioral functioning were impaired. Intelligence was lower in the polypharmacy group, while other functions were similar. In the second assessment, intelligence and visual memory improved in the monotherapy group, while no changes were present in the polypharmacy group.

The blink reflex and somatosensory evoked potential in optic neuritis in south India.

Optic Neuritis (ON) proceeds to multiple sclerosis (MS) in a considerable number of patients. The blink reflex (BR) and somatosensory evoked potential (SSEP) are useful non-invasive tests that can detect silent lesions in the central nervous system in patients with clinically suspect MS. In the present study, the BR and SSEP were done in 20 healthy controls and 20 patients with ON. Abnormalities of the SSEP were seen in 20%, and of the BR in 30% of the patients with ON. On combining the results of SSEP and BR studies, 45% of the ON patients were seen to have abnormalities. Over a short period of follow-up, 2 of the 20 ON patients developed clinical MS and both of them had had abnormalities of the BR. These findings suggest that ON proceeding to MS in India may be more common than suspected at present.