Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection

Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5?mg/ml and 10?mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.     

Unilateral proptosis secondary to diffuse condensing osteomyelitis

Osteomyelitis of the skull is an uncommon disease in the present days, mainly due to the advent of modern and more effective antibiotics. Hematogenous osteomyelitis is very rare. Osteomyelitis of the skull is usually not associated with sclerosis which is commonly seen in the rest of the skeleton. There are only few occasional case reports of condensing osteomyelitis wherein there was sclerosis of the bone associated with osteomyelitis of the skull and epidural abscess. An unusual case of diffuse condensing osteomyelitis of the skull producing unilateral proptosis is reported. The clinical, radiological features and microbiological aspects are presented. The proptosis was treated by excision of the bone behind the eyeball and thus relieving the proptosis and the impaired vision. The patient was given broad spectrum antibiotics for a period of two months. Further management problems are discussed.     

Nutrition, health and psychosocial profile of institutionalized children.

A study was undertaken to assess the health, nutrition and psychosocial profile of Institutionalized children in four States--Uttar Pradesh, Andhra Pradesh, Karnataka and West Bengal. A sample of 3,822 children from 70 institutions in 6-18 years age group formed the subjects of the study. It was observed that the destitute children were mainly taken care of in three types of institutions, viz, Voluntary, Government Aided and Government run institutions. Calorie deficiency and deficiency of Vitamins and minerals characterized the diets of these children. In general, there was no deficit of protein in their diets. Growth wise, these children were retarded both in height and weight compared to standards. However, they fared better in comparison to their age and sex counterparts in the rural and urban poor. Psychosocial profile of these children indicated that the prevailing environment in the institutions is less conducive for intellectual stimulation but not so for the development of skills of self-help, locomotion, socialization and imagery.     

Identification of T-cell epitopes without B-cell activity in the first and second conserved regions of the HIV Env protein.

We have previously hypothesized that an effective vaccine against HIV should elicit cell-mediated immunity without antiviral antibody production. As a first step towards this goal we have identified potential T-cell epitopes, without B-cell activity against the native protein, from the first and second conserved sequences, and from three functionally important regions of the HIV-1 envelope protein gp160. For this approach, short peptide sequences selected by established computer programs were synthesized and chemically modified to generate either polymers with disulfide bonds, or micelles with two palmitic acid residues attached to the amino-terminal lysine. In both configurations several peptides were immunogenic without the need for coupling to carrier molecules. Of the 19 peptides we tested in our present studies, seven induced good T-cell proliferative response in mice representing four major histocompatibility complex haplotypes. None of these seven peptides produced antibodies that could recognize the envelope protein gp160.     

P-glycoprotein (MDR 1 gene product) in cells of the immune system: Its possible physiologic role and alteration in aging and human immunodeficiency virus-1 (HIV-1) infection

P-glycoprotein, a 170-kd glycoprotein encoded by theMDR 1 gene, is a member of a highly conserved superfamily of ATP-binding cassette (ABC) transport proteins. It shares extensive homology with numerous bacterial and eukaryotic ABC transport proteins. P-glycoprotein acts as an energy-dependent efflux pump that appears to transport structurally diverse agents ranging from ions to peptides. P-glycoprotein (P-gP) has been implicated as playing a role in multidrug (MDR) resistance in cancer, chloroquine-resistantPlasmodium falciparum infection, and possibly human immunodeficiency virus-1 (HIV-1) resistance to nucleoside compounds. A number of normal tissues in humans and rodents have been shown to express high levels of P-gp. The expression and function of P-gp in cells of the immune system have been explored in the past 2 years. This review presents a state of the art regarding the expression, regulation, and function of Pgp in cells of the immune system. In addition, its alteration in aging and HIV-1 infection is reviewed. A possible physiologic role of P-gp in cytokine secretion, antigen processing/presentation, and effector functions is also discussed.     

Isolation, distribution and prevalence of various species of enterococci isolated from clinical specimens in a tertiary care hospital

Various clinical specimens were processed to find the prevalence rate of enterococci and to identify the species of clinical isolates of enterococci. Screening of various clinical specimens revealed that enterococci were prevalent in 2% of the total specimens, with urine and wound to be the major site of isolation. Conventional test scheme proposed by Facklam and Collins and commercially available systems Rapid ID 32 Strep (biomereiux) were successfully used to speciate enterococcal strains. Five species of enterococci were identified in the study from a set of 396 cultures, with E. faecalis (79.79%), and E. faecium (11.11%) predominating. E. hirae (3.03%), E. gallinarum (3.03%), and E. casseliflavus (3.03%), were the other members of Enterococcus species identified.     

Inhibition of pilus-mediated adhesion of Pseudomonas aeruginosa to human buccal epithelial cells by monoclonal antibodies directed against pili.

The Pseudomonas aeruginosa PAK pilus is capable of mediating the binding of this strain to human respiratory epithelial cells. We have produced monoclonal antibodies (MAbs) to the PAK pilus in order to elucidate the location of the binding domain of the pilus for human buccal epithelial cells (BECs). Four MAbs are described. MAbs PK41C and PK34C were found to react with P. aeruginosa pilins produced by a large number of strains. The epitope recognized by PK41C was determined to lie within the N-terminal region of the pilin and is likely constituted by amino acid residues 22 through 33. The epitope for PK34C was located in the C-terminal region of the pilin and was partially dependent on an intact intrachain disulfide bridge between cysteine residues 129 and 142. PK99H and PK3B were found to react specifically with PAK pilin. The epitope for PK99H was also localized in the C-terminal region of the pilin protein and appears to reside between amino acid residues 130 and 138. The epitope for PK3B was not localized by using the methods of this study, but it is likely dependent on the three-dimensional structure of the pilin. Fab fragments of PK99H inhibited adhesion of strains PAK and 492c to BECs, but the adherence of five other strains was not affected. Fab fragments of PK34C inhibited adhesion of all piliated strains examined. Fab fragments from both of these antibodies inhibited PAK pilus binding to BECs. Fab fragments of PK41C and PK3B had no effect on P. aeruginosa binding to BECs. These results confirm that the C-terminal region of the pilin has adhesin qualities and that a conserved epitope lies within this region.