Characterization of pilocarpine-loaded chitosan/Carbopol nanoparticles

Patients using ophthalmic drops are faced with frequent dosing schedules and difficult drop instillation. Therefore, a long-lasting pilocarpine-loaded chitosan (CS)/Carbopol nanoparticle ophthalmic formulation was developed. The physicochemical properties of the prepared nanoparticles were investigated using dynamic light scattering, zeta-potential, transmission electron microscopy, Fourier transform infrared ray spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The sustained-release effects of pilocarpine-loaded nanoparticles were evaluated using in-vitro release and in-vivo miotic tests, and compared with pilocarpine in solution, gel and liposomes. We found that the prepared nanoparticles were about 294 nm in size. DSC and FT-IR studies suggested that an electrostatic interaction between CS and Carbopol contributes at least in part to the stabilization of pilocarpine/CS/Carbopol nanoparticles. When compared with pilocarpine in solution, gel or liposomes, the best slow-release profile of pilocarpine from the prepared nanoparticles occurred in a dissolution test. In the in-vivo miotic study, pilocarpine-loaded CS/Carbopol nanoparticles showed the most significant long-lasting decrease in the pupil diameter of rabbits. The advantages of CS and Carbopol are good biocompatibility, biodegradability and low toxicity. CS is also a mucoadhesive polymer. Thus, pilocarpine/CS/Carbopol nanoparticles may provide an excellent potential alternative ophthalmic sustained-release formulation of pilocarpine for clinical use. CS/Carbopol nanoparticles may also be useful for a variety of other therapeutic delivery systems.     

Long-lasting neurotoxicity of prenatal benzene acute exposure in rats

Benzene is a common element of environmental pollution. Although this substance is not recognized as a teratogenic agent, it is not known whether prenatal exposure to benzene may induce neurobehavioral changes in the progeny. Benzene 0.1mg/kg was injected subcutaneously (s.c.) acutely at day 15 of gestation into pregnant female rats of the Sprague-Dawley strain and neurotoxicity of the substance was studied in pups and male adult animals of the same progeny. No change was found in total number of neonates, body weight and eye opening time between benzene-exposed animals and controls. No malformations were observed. At birth, neonatal reflexes (cliff aversion, forelimb placing, bar holding, forelimb grasping, startle) were scored in benzene-exposed pups and their percent appearance was found to be anticipated (more benzene-exposed pups exhibited reflexes each day) in comparison to that of control animals. Also, the completion (maximum appearance, i.e. 100% of the brood was found to exhibit each reflex) of neonatal reflexes in benzene-exposed animals preceded that of controls. Starting 2 months after birth, cognitive and motor performance was assessed only in male animals of the prenatally benzene-exposed progeny. The overall evaluation of motor activity in benzene-exposed animals in the open-field test revealed reduced ambulation in these rats as compared to control animals. Acquisition of active avoidance responses in the shuttle-box test, as assessed by the number of conditioned avoidance responses and the percent of learners, was impaired in benzene-exposed rats as compared to control animals. Prenatal exposure to benzene was also followed by reduced retention latency in a step-through passive avoidance task in two retention tests. These results suggest that acute exposure to benzene during gestational organogenesis may cause long-lasting changes in motor behavior and cognitive processes. This may be relevant for the assessment of benzene toxic profile for the progeny of pregnant subjects, although teratogenic effects are not observed.     

Matrix protein 2 vaccination and protection against influenza viruses, including subtype H5N1

Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that crossreacted with human and avian M2 sequences and produced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A.     

Experience of hepatitis A vaccination during an outbreak in a nursery school of Tuscany,Italy.

An outbreak of hepatitis A started in late October 1996 in a nursery school in Tuscany, Italy. A programme of hepatitis A vaccination without the use of immunoglobulin started at the beginning of December 1996 and included 33 children, 21 household contacts and 6 adults working in the school. Overall, 11 cases occurred in children attending the school (attack rate 27%) and 10 among their household contacts (attack rate 9 %). The latter also included parents, and, in two cases, grandmothers. The data indicate that susceptibility to HAV has increased over recent decades in central Italy. Past and recent experience shows that the usual duration of hepatitis A epidemics in the absence of immune prophylaxis is longer than that described here. The use of hepatitis A vaccine probably contributed to the early extinction of the outbreak, because no further cases were notified in the area after 7 February 1997.     

Susceptibility variants for waist size in relation to abdominal, visceral, and hepatic adiposity in postmenopausal women

Genome-wide association studies have identified common genetic variants that can contribute specifically to the risk of abdominal adiposity, as measured by waist circumference or waist-to-hip ratio. However, it is unknown whether these genetic risk factors affect relative body fat distribution in the abdominal visceral and subcutaneous compartments. The association between imaging-based abdominal fat mass and waist-size risk variants in the FTO, LEPR, LYPLAL1, MSRA, NRXN3, and TFAP2B genes was investigated. A cross-sectional sample of 60 women was selected among study participants of The Multiethnic Cohort, who were aged 60 to 65 years, of European or Japanese descent, and with a body mass index (calculated as kg/m(2)) between 18.5 and 40. Dual-energy x-ray absorptiometry and abdominal magnetic resonance imaging scans were used to measure adiposity. After adjustments for age, ethnicity, and total fat mass, the FTO variants showed an association with less abdominal subcutaneous fat and a higher visceral-to-subcutaneous abdominal fat ratio, with the variant rs9941349 showing significant associations most consistently (P=0.003 and 0.03, respectively). Similarly, the LEPR rs1137101 variant was associated with less subcutaneous fat (P=0.01) and a greater visceral-to-subcutaneous fat ratio (P=0.03) and percent liver fat (P=0.007). MSRA rs545854 variant carriers had a lower percent of leg fat. Our findings provide initial evidence that some of the genetic risk factors identified for larger waist size might also contribute to disproportionately greater intra-abdominal and liver fat distribution in postmenopausal women. If replicated, these genetic variants can be incorporated with other biomarkers to predict high-risk body fat distribution.     

Assessing psychosocial well-being of adolescents: a systematic review of measuring instruments

Background The paradigm shift from the clinically deficit‐oriented approach to that of educationally strength‐based model in assessing adolescents' psychosocial well‐being has brought about a recent increase in school‐based health promotion and prevention initiatives. This prompted this systematic review of measuring instruments designed to assess psychosocial well‐being of children and adolescents. Methods Using electronic databases on Academic Search Premier, MEDLINE, PROQUEST, PsycINFO, CINAHL Plus and Psychosocial and Health Instrument, a systematic review of literature of measuring instruments was conducted from their inception to December 2009 using the keywords of child, emotion, assessment, scale and measure. Measuring instruments from selected articles were critically appraised using a predetermined set of quality indicators which guided the rating of the psychometric properties of the instruments into grades of A, B, and C. The constructs of psychosocial well‐being from the measuring instruments were categorized into themes. Results Twenty‐nine out of the 908 articles met the inclusion criteria. Seventeen instruments identified from the selected articles were examined using preset quality indicators. In construct building, the themes identified from the strength‐based instruments distinguished the construct of psychosocial well‐being primarily into the dimensions of personal emotional competency and social functioning. In the ratings of psychometric properties, one instrument was rated 5A, five rated 4A and four rated 3A. For reliability testing, eight measures received grade A when their intraclass correlation is higher than 0.7; whereas only two instruments reported sensitivity and none investigated responsiveness. Conclusions Strength‐based measures focusing on social emotional behavioural outcomes open up a possibility to link up assessment with promotion of psychosocial well‐being, away from clinical settings and into adolescents' homes, schools and community. Future research should focus more on investigating the sensitivity and responsiveness of measuring instruments using longitudinal design in efficacy studies to assess change in adolescents' psychosocial status over extended time.     

Pregnant women living in areas of endemic fluorosis in Senegal and low birthweight newborns: case-control study

BackgroundIn developing countries, maternal and neonatal mortality is high. Among the causes of death during the neonatal period, low birth weight is crucial. A dose of fluoride beyond 2 mg/L causes enamel damage, possibly affecting the fetus. The aim of this study was to search for an association between dental fluorosis in the mother and low birthweight of the newborn.MethodologyThis was a case–control study performed in an endemic area in Senegal (Diourbel). It included 108 mothers who gave birth to newborns weighing less than 2500 g (cases) and 216 mothers with newborns weighing greater or equal to 2500 g (controls). Data on socio-demographic, lifestyle, history and pregnancy variables were collected. Those related to water consumption during pregnancy and dental fluorosis (Dean's index) were measured. The data were analyzed by R software. Logistic regression was used to identify associations and the statistical significance level was set to 0.05.ResultsThe proportions of mothers consuming well water were 62% among cases versus 43.5% among controls. The score 4 of Dean's Index was reported for 25.9% of cases versus 6.9% of controls. The water consumed and the modal score of Dean's Index were significantly associated with the occurrence of low birthweight adjusted for gender, consanguinity, anemia and hypertension.ConclusionLow birthweight was associated with pregnant women living in endemic areas. Defluoridation programs and access for pregnant women and children to high quality water are necessary in areas of endemic fluorosis.