Abstract This review shall familiarize the readers with various fundamental aspects of angiogenesis. Angiogenesis is a feature of a limited number of physiological processes like wound healing, ovulation, development of the corpus luteum, embryogenesis, lactating breast, during immune response, and during Inflammation. It is driven by a cocktail of growth factors and pro-angiogenic cytokines and is tempered by an equally diverse group of inhibitors of neovascularization. The properties and biological functions of angiogenic growth factors such as VEGF, FGF-2, nitric oxide, MMP, angiopoietin, TGF-beta as well as various inhibitors such as angiostatin, endostatin, thrombospondin, canstatin, DII4, PEDF are discussed in this review with respect to their impact on angiogenic process. In recent years, it has become increasingly evident that excessive, insufficient, or abnormal angiogenesis contributes to the pathogenesis of many more disorders. A long list of disorders is characterized or caused by excessive or insufficient angiogenesis whereas several congenital or inherited diseases are also caused by abnormal vascular remodeling. It may be possible in the future to develop specific anti-angiogenic agents that offer a potential therapy for cancer and angiogenic diseases.

Relatively little is known about exposures to traffic-related particulate matter at schools located in dense urban areas. The purpose of this study was to examine the influences of diesel traffic proximity and intensity on ambient concentrations of fine particulate matter (PM(2.5)) and black carbon (BC), an indicator of diesel exhaust particles, at New York City (NYC) high schools. Outdoor PM(2.5) and BC were monitored continuously for 4-6 weeks at each of 3 NYC schools and 1 suburban school located 20 kilometers upwind of the city. Traffic count data were obtained using an automated traffic counter or video camera. BC concentrations were 2-3 fold higher at urban schools compared with the suburban school, and among the 3 urban schools, BC concentrations were higher at schools located adjacent to highways. PM(2.5) concentrations were significantly higher at urban schools than at the suburban school, but concentrations did not vary significantly among urban schools. Both hourly average counts of trucks and buses and meteorological factors such as wind direction, wind speed, and humidity were significantly associated with hourly average ambient BC and PM(2.5) concentrations in multivariate regression models. An increase of 443 trucks/buses per hour was associated with a 0.62 mug/m(3) increase in hourly average BC at a NYC school located adjacent to a major interstate highway. Car traffic counts were not associated with BC. The results suggest that local diesel vehicle traffic may be important sources of airborne fine particles in dense urban areas and consequently may contribute to local variations in PM(2.5) concentrations. In urban areas with higher levels of diesel traffic, local, neighborhood-scale monitoring of pollutants such as BC, which compared to PM(2.5), is a more specific indicator of diesel exhaust particles, may more accurately represent population exposures.

The aim of the present study was to prepare and evaluate microspheres of Eudragit containing an antiviral drug stavudine. Microspheres were prepared by O/O solvent evaporation method using acetone/liquid paraffin system. The prepared microspheres were characterized for their micromeretic properties and entrapment efficiency; as well by Fourier transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD) and scanning electron microscopy (SEM) which revealed the crystalline nature of drug in a final state. The in vitro studies revealed the controlled release of drug from microspheres up to 12 h and the best fit release kinetics was achieved with a Higuchi plot and found to be diffusion controlled. The yields of preparation and entrapment efficiencies were very high with a larger particle size for all the formulations. Mean particle size, entrapment efficiency and production yield were highly influenced by the type of polymer and polymer concentration.

Objective: The goal was to assess the effectiveness of complete (3-dose) or partial (1- or 2-dose) immunization with pentavalent rotavirus vaccine (RV5) against rotavirus acute gastroenteritis (AGE) in US clinical practice. Methods: A case-control evaluation was conducted in February through June 2008 at an emergency department in Houston, Texas. Case patients with rotavirus AGE (N = 90) were identified through testing for rotavirus in fecal specimens obtained from 205 children 15 days through 23 months of age presenting with AGE. Control groups included rotavirus-negative AGE patients (N = 115), concurrently enrolled patients with acute respiratory infection (ARI)(N = 228), and up to 10 age- and zip code-matched children sampled from the Houston-Harris County Immunization Registry (HHCIR) for each case patient >8 months of age. Immunization data were obtained from parent records, health care providers, and/or the HHCIR. Vaccine effectiveness was calculated as 1 minus odds of RV5 vaccination for case patients versus control patients, after adjustment for age at presentation and birth date. Results: The vaccine effectiveness of a complete RV5 series was 89%(95% confidence interval [CI]: 70%-96%) and 85%(95% CI: 55%-95%) with rotavirus-negative AGE and ARI control patients, respectively. Immunization data were available for 44% of case patients (n = 40) from the HHCIR; the estimated 3-dose vaccine effectiveness with these HHCIR control patients was 82%(95% CI: 19%-96%). A complete RV5 series conferred 100% protection (95% CI: 71%-100%) against severe rotavirus disease requiring hospitalization and 96% protection (95% CI: 72%-99%) against disease requiring intravenous hydration. Vaccine effectiveness of 1 and 2 doses against hospitalization and emergency department visits was 69%(95% CI: 13%-89%) and 81%(95% CI: 13%-96%), respectively, using rotavirus-negative AGE and ARI control groups combined. Conclusions: In this setting, a complete series of RV5 was highly effective against severe rotavirus AGE. Partial immunization also conferred substantial protection.

Ubiquitin-interacting motifs (UIMs) are an important class of protein domains that interact with ubiquitin or ubiquitin-like proteins. These approximately 20 residue-long domains are found in a variety of ubiquitin receptor proteins and serve as recognition modules towards intracellular targets, which may be individual ubiquitin subunits or polyubiquitin chains attached to a variety of proteins. Previous structural studies of the interactions between UIMs with ubiquitin have shown that UIMs adopt an extended structure of a single alpha-helix, containing a hydrophobic surface with a conserved sequence pattern that interacts with key hydrophobic residues on ubiquitin. In light of this large body of structural studies, details regarding the presence and roles of structural dynamics and plasticity are surprisingly lacking. In order to better understand the structural basis of ubiquitin-UIM recognition, changes in the structure and dynamics of ubiquitin have been characterized upon binding of a UIM domain from the yeast Vps27 protein. The solution structure of a ubiquitin-UIM fusion protein designed to study these interactions is reported here and found to consist of a well-defined ubiquitin core and a bipartite UIM helix. Moreover, we have studied the plasticity of the docking interface as well as global changes in ubiquitin due to UIM binding at the picosecond to nanosecond and microsecond to millisecond protein motions by NMR relaxation. Changes in generalized order parameters of amide groups show a distinct trend toward increased structural rigidity at the UIM-ubiquitin interface relative to values determined in unbound ubiquitin. Analysis of (15)N CPMG relaxation dispersion measurements suggest the presence of two types of motions, one directly related to the UIM-binding interface, the other being induced to distal parts of the protein. This study demonstrates a case where localized interactions among protein domains have global effects in protein motions at timescales ranging from picoseconds to milliseconds.

Background. In a Latin American trial, a monovalent G1P[8] rotavirus vaccine showed high efficacy against severe rotavirus diarrhea. Protection was lower against serotypically unrelated G2P[4] strains, which circulated infrequently. This case-control study was undertaken to assess the effectiveness of this monovalent G1P[8] rotavirus vaccine against G2P[4] strains in Brazil. Methods. Case patients were children with severe G2P[4] rotavirus diarrhea who presented at a hospital in Recife, Brazil, from March 2006 through September 2008. Vaccination rates among case patients were compared with rates among 2 groups of control participants-children with rotavirus-negative diarrhea and children admitted for acute respiratory tract infection (ARI)-to calculate vaccine effectiveness, after controlling for the birth month and year. Results. We enrolled 70 G2P[4] rotavirus-positive case patients with severe diarrhea, 484 rotavirus-negative control participants with diarrhea, and 416 control participants with ARI, aged 6 months. Among children aged 6-11 months, the effectiveness of the vaccine against G2P[4] diarrhea was 77%(95% confidence interval [CI], 42%-91%) and 77%(95% CI, 43%-90%) among the rotavirus-negative control participants with diarrhea and control participants with ARI, respectively. Vaccine effectiveness in children aged 12 months decreased to -24%(95% CI,-190% to 47%) and 15%(95% CI,-101 to 64) among the rotavirus-negative control groups with diarrhea and ARI, respectively. Conclusions. This monovalent G1P[8] rotavirus vaccine was effective against severe G2P[4] rotavirus diarrhea among children aged 6-11 months. Effectiveness declined among children aged 12 months, which suggests waning immunity.

Two live oral rotavirus vaccines (RotaTeq) and Rotarix) have recently been recommended by the WHO for inclusion into the national immunization programs of countries worldwide. Owing to the association of the withdrawn Rotashield vaccine with intussusception, these two new rotavirus vaccines underwent large clinical trials of over 60,000 infants each to assess safety with regard to this medical condition. For these two new vaccines, clinical trials and available postmarketing safety monitoring data do not indicate a risk of intussusception after vaccination, although a low-level risk cannot be excluded at present. We review these safety data for the new vaccines and for Rotashield to provide background information relevant for considering age recommendations for rotavirus vaccination.

Mucoadhesive buccal patches containing propranolol hydrochloride were prepared using the solvent casting method. Chitosan was used as bioadhesive polymer and different ratios of chitosan to PVP K-30 were used. The patches were evaluated for their physical characteristics like mass variation, drug content uniformity, folding endurance, ex vivo mucoadhesion strength, ex vivo mucoadhesion time, surface pH, in vitro drug release, and in vitro buccal permeation study. Patches exhibited controlled release for a period of 7 h. The mechanism of drug release was found to be non-Fickian diffusion and followed the first-order kinetics. Incorporation of PVP K-30 generally enhanced the release rate. Swelling index was proportional to the concentration of PVP K-30. Optimized patches (F4) showed satisfactory bioadhesive strength of 9.6 +/- 2.0 g, and ex vivo mucoadhesion time of 272 minutes. The surface pH of all patches was between 5.7 and 6.3 and hence patches should not cause irritation in the buccal cavity. Patches containing 10 mg of drug had higher bioadhesive strength with sustained drug release as compared to patches containing 20 mg of drug. Good correlation was observed between the in vitro drug release and in vitro drug permeation with a correlation coefficient of 0.9364. Stability study of optimized patches was done in human saliva and it was found that both drug and buccal patches were stable.

Objectives: The goals were to assess, among pediatricians and family medicine physicians,(1) rates of offering the vaccine in their office;(2) knowledge of Advisory Committee on Immunization Practices recommendations;(3) barriers to use; and (4) factors associated with offering the vaccine. Methods: Surveys of pediatricians and family medicine physicians were conducted in August to October 2007. Results: Response rates were 84% for pediatricians and 79% for family medicine physicians (N = 623). Proportions routinely offering the vaccine were 85% of pediatricians and 45% of family medicine physicians (P <.0001); 70% of pediatricians and 22% of family medicine strongly recommended the vaccine (P <.0001). Sixty-two percent of pediatricians and 32% of family medicine physicians (P <.0001) knew the age by which all 3 doses should be completed. Definite barriers to vaccine use included reported lack of coverage by insurance companies (family medicine physicians: 22%; pediatricians: 19%; not significant), costs of purchasing vaccine (family medicine physicians: 22%; pediatricians: 17%; not significant), lack of adequate reimbursement (family medicine physicians: 18%; pediatricians: 15%; not significant), concerns about safety (family medicine physicians: 25%; pediatricians: 9%; P <.0001), and concerns about adding another vaccine to the schedule (family medicine physicians: 22%; pediatricians: 5%; P <.0001). Conclusions: Rates of offering the new rotavirus vaccine are high among pediatricians but <50% among family medicine physicians. Both specialties identified financial barriers to use of the vaccine, but family medicine physicians had significantly more concerns about safety and about adding another vaccine to the vaccination schedule.