Monoclonal antibodies to gonadotropin-releasing hormone (GnRH) inhibit binding of the hormone to its receptor

Monoclonal antibodies (MAbs) specific to gonadotropin-releasing hormone (GnRH) were obtained using different strategies of conjugation of the peptide to carrier protein and immunization. Of several antibodies obtained, two, namely F1D3C5 and E2D2 bound GnRH in solution phase. Though the epitopes corresponding to the two overlapped, there was a one amino acid shift in the core epitope. These two antibodies were characterized with respect to inhibition of GnRH induced responses in rat pituitary cultures and alpha-T3.1 mouse gonadotrope cell line.     

Intracameral 2.3% sodium hyaluronate to treat postoperative hypotony in patients with glaucoma.

BACKGROUND AND OBJECTIVE: To evaluate the intracameral use of Healon5 (2.3% sodium hyaluronate) (Advanced Medical Optics, Santa Ana, CA) in patients with hypotony. PATIENTS AND METHODS: Fifteen consecutive patients with glaucoma who had hypotony for at least 7 days were prospectively recruited. Indications for the intracameral injection of Healon5 were an intraocular pressure (IOP) of less than 6 mm Hg with negative results on Seidel test. RESULTS: The mean IOP readings at baseline, 1 to 2 weeks post-injection, and 4 to 6 weeks post-injection were 3.8 +/- 1.58, 6.58 +/- 2.62, and 6.50 +/- 2.24 mm Hg, respectively. The increase in IOP at both follow-up points was significant (P < .01). The visual acuity improvement was small but significant at the 4 to 6 week point (P = .05). In the early-onset cases, IOP increased significantly from baseline at both follow-up points (P< .05), but visual acuity did not. No significant change from baseline IOP or visual acuity occurred among the late-onset cases. The existing hypotony-related conditions consistently improved by the 4 to 6 week point. CONCLUSIONS: Intracameral injection of Healon5 raised IOP more in early-onset hypotony cases than in late-onset cases. Although the improvements in IOP and visual acuity were statistically significant, the overall clinical picture did not change because the endpoint IOP was still hypotonus. Twenty percent of the patients had IOP spikes that required medical treatment.     

Long-circulating polymeric nanovectors for tumor-selective gene delivery

Significant advances in the understanding of the genetic abnormalities that lead to the development, progression, and metastasis of neoplastic diseases has raised the promise of gene therapy as an approach to medical intervention. Most of the clinical protocols that have been approved in the United States for gene therapy have used the viral vectors because of the high efficiency of gene transfer. Conventional means of gene delivery using viral vectors, however, has undesirable side effects such as insertion of mutational viral gene into the host genome and development of replication competent viruses. Among non-viral gene delivery methods, polymeric nanoparticles are increasingly becoming popular as vectors of choice. The major limitation of these nanoparticles is poor transfection efficiency at the target site after systemic administration due to uptake by the cells of reticuloendothelial system (RES). In order to reduce the uptake by the cells of the RES and improve blood circulation time, these nanoparticles are coated with hydrophilic polymers such as poly(ethylene glycol) (PEG). This article reviews the use of such hydrophilic polymers employed for improving the circulation time of the nanocarriers. The mechanism of polymer coating and factors affecting the circulation time of these nanocarriers will be discussed. In addition to the long circulating property, modifications to improve the target specificity of the particles and the limitations of steric protection will be analyzed.     

Television health promotion in four countries

OBJECTIVE: The research plan was to conduct a comparative, longitudinal field experiment in Russia, Hungary, the Czech Republic, and Poland to evaluate the effect of a nutritional and general health promotion television series. The series addressed four health topics: a healthy diet, avoidance of tobacco use and alcohol abuse, and enhanced physical activity. METHODS: Because of different infrastructure and contingency conditions in the four countries, data collection ranged from group-administered surveys at a central location to individual personal interviews using a quasi-experiment comparing viewers and non-viewers 18 y and older. It occurred between 1996 and 1998. RESULTS: Overall, the television programs were found to provide new, useful, and practical information to viewers. Most (53.4% to 64.0%) learned useful information. Nearly 33% or more (29.5% to 37.9%) intended to change their lifestyle, with about 25% or more (24.0% to 60.2%) of this group indicating that they would eat more fruits and vegetables. Subsequently, 16.7% to 45.0% reported actual dietary changes consistent with health promotion. CONCLUSIONS: The study addressed diet and nutritional patterns in this region and the underlying social and behavioral factors, topics on which there is very limited information. Methodologic equivalence was sought through consistent measures despite the differential research infrastructure in the four countries. Results indicated that viewers rated the nutritional and general health promotion television programs favorably and that media messages can be used to motivate and educate viewers. More sustained television programs focused on health promotion will benefit audiences in Central and Eastern Europe.     

Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14

Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry. In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period. The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor-beta1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas. These results suggest that, in addition to p57/KIP2, EGCG-induced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications.     

Effect of nutrition education of mothers on infant feeding practices

Objective : To assess current infant feeding practices (IFP) in a relocated slum, to identity the lacunae, to outline, implement, and evaluate the gain in awareness and IFP followed by mothers.Methods. Thirty–five mothers of infants aged 5–19 months were interviewed. Based on lacunae, Nutrition Education (NE) was imparted to mothers over two months. Tools used were individual counseling, participatory learning methods, positive deviance and early adopters approach aided with existing information education communication materials. Monthly weight and length of infants was also taken. Awareness and practices on infant feeding (IF) were reviewed at mid and post NE.Results. Areas of concern at baseline were (i) discarding colostrum (77.0%), (ii) feeding prelacteals (80.0%), (iii) initiation of breast-feeding (BF) after 3 days (54.3%), (iv) absence of exclusive breast-feeding (86.3%), (v) delayed complementary feeding (CF) and (vi) feeding CF grossly inadequate in quality, quantity, frequency and consistency. Post NE results revealed an improved awareness about IF amongst the mothers. An improvement was seen in variety, quantity and consistency of CF fed. Active feeding behaviours were adopted (6.6% pre-NE vs 66.6% post-NE). Early adopters (24%) served as motivators. Weight for age and weight for length showed improvement.Conclusion : NE programs of shorter duration using a ‘communication mix’ of channels with repeated reinforcement can bring about improvement not only in awareness but also in IFP.     

Propofol for pediatric radiotherapy

Objective : Pediatric radiotherapy is a day care procedure. In children, anaesthesia is necessary to prevent movement during the therapy. Traditionally intramuscular ketamine is used for these procedure because of its inherent safety in a child who used to be left alone in the cobalt room.Methods : This study was designed to explore the efficacy of propofol and ketamine in pediatric radiotherapy in nineteen children. The inclusion criteria was a child fasting for six hours with no fever or URTI in the past week. A child coming to the radiotherapy (RT) unit without an intravenous cannula was given intramuscular ketamine 10 mg/kg and taken for the procedure. Before the child recovered from anaesthesia an intravenous cannula, 20–22G, Vasofix was inserted for subsequent sittings of RT. The child coming with an intravenous cannula was given propofol 2.5 mg/kg with xylocaine (0.1 mg/kg) without adrenaline. The parameters recorded were pulse rate, oxygen saturation and respiratory rate-baseline to every 30 seconds till five minutes. Onset time, recovery time, oral feeding time and any untoward effects like nausea, vomiting, nystagmus were also noted.Result: The drug was graded on a scale of 0–10 according to parental acceptability where 0 is the worst and 10 is the best acceptability. The mean (±SD) of all the measured parameters were calculated and compared between the two groups.Conclusion : Propofol was associated with faster onset, better recovery, early oral feeding time, no nausea and vomiting and better parental acceptability. There was no hypotension, bradycardia and oxygen saturation at 60 seconds, which was betwen 94–95%, was easily treatable with supplementation of oxygen by face mask     

Downregulation of uPA inhibits migration and PI3k/Akt signaling in glioblastoma cells

The ability of glioma cells to migrate great distances from a primary tumor mass is the primary cause of tumor recurrence. The urokinase-type plasminogen activator (uPA) is a serine protease that can initiate proteolytic cascades, which result in remodeling of extracellular matrix and basement membrane, allowing cells to move across and through these barriers. The binding between uPA and its receptor uPAR also mediates several signaling events that seem to contribute to the evolution of a migratory phenotype. In this study, we determined how the downregulation of uPA affects the signaling pathways leading to cell migration. Stably transfecting human glioblastoma cells with antisense uPA decreased the amount of cell-bound uPA and disrupted actin cytoskeleton formation and cell migration. The phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathway has been suggested to mediate migration in various cancer cells. The antisense-uPA clones also had less phosphorylated PI3k and Akt than control cells, a finding associated with decreased cell migration, G2/M-phase arrest, and decreased clonogenic survival. Decreased activation of PI3k and the antiapoptotic factor Akt was not sufficient to induce apoptosis in the antisense-uPA clones, but staurosporine sensitized them to apoptosis to a greater extent than control cells. These results indicate that PI3k/Akt pathway is involved in the signaling cascade required to induce cell migration and that uPA has a direct role in regulating migration.