PHARMACEUTICAL AND BIOPHARMACEUTICAL ASPECTS OF QUANTUM DOTS-AN OVERVIEW

In the twenty-first century, nanotechnology has become cutting-edge technology. It is interdisciplinary and multidisciplinary, covering numerous fields such as medicine, engineering, biology, physics, material sciences, and chemistry. The present work aims to cover the optical properties, method of preparations, surface modifications, bio-conjugation, characterization, stability, and cytotoxicity of quantum dots (QDs). Articles were reviewed in English literature reporting the pharmaceutical and bio-pharmaceutical aspects of QDs which were indexed in Scopus, web of science, google scholar and PubMed without applying the year of publication criterion. One significant value of utilizing nanotechnology is that one can alter and control the properties in a genuinely unsurprising way to address explicit applications' issues. In science and biomedicine, the usage of functional nanomaterials has been broadly investigated and has become one of the quick-moving and stimulating research directions. Different types of nanomaterial (silicon nanowires, QDs, carbon nanotubes, nanoparticles of gold/silver) were extensively utilized for biological purposes. Nanomedicine shows numerous advantages in the natural characteristics of targeted drug delivery and therapeutics. For instance, protection of drugs against degradation, improvement in the drug's stability, prolonged circulation time, deceased side effects, and enhanced distribution in tissues. The present review article deals with the quantum dots, their optical properties, method of preparations, surface modifications, bio-conjugation, characterization, stability, and cytotoxicity of quantum dots. The review also discusses various biomedical applications of QDs. The QDs-based bio-nanotechnology will always be in the growing list of unique applications, with progress being made in specialized nanoparticle development, the detection of elegant conjugation methods, and the discovery of new targeting ligands

Chandipura virus: a major cause of acute encephalitis in children in North Telangana, Andhra Pradesh, India

A hospital-based surveillance was undertaken between May 2005 and April 2006 to elucidate the contribution of Chandipura virus (CHPV) to acute viral encephalitis cases in children, seroconversion in recovered cases and to compare the seroprevalences of anti-CHPV IgM and N antibodies in areas reporting cases with those without any case of acute viral encephalitis. During this period, 90 cases of acute encephalitis were hospitalized in the pediatric wards of Mahatma Gandhi Memorial (MGM) Hospital, Warangal. There were 49 deaths (Case Fatality Rate, i.e., CFR of 54.4%). Clinical samples and records were obtained from 52 suspected cases. The cases were below 15 years, majority in 0-4 years (35/52, 67.3%). Computerized tomography (CT) scans and cerebro-spinal fluid (CSF) picture favored viral etiology. No neurological sequelae were observed. CHPV etiology was detected in 25 cases (48.1%, n = 52; RNA in 20, IgM in 3 and N antibody seroconversion in 2). JEV etiology was detected in 5 cases (IgM in 4 cases and seroconversion in 1 case). Anti-CHPV IgM seroprevalence in contacts (26/167, 15.6%) was significantly higher (P < 0.05) than in non-contacts (11/430, 2.6%); which was also observed in children < 15 years (19/90, 21.1% vs. 3/109, 2.7%). Anti-CHPV N antibody seroprevalence in <15 years contacts (66/90, 73.3%) and non-contacts (77/109, 70.6%) was significantly lower (P < 0.05) than in contacts (75/77, 97.4%) and non-contacts (302/321, 94.1%) more than 15 years respectively. CHPV appears to be the major cause of acute viral encephalitis in children in endemic areas during early monsoon months

Prevalence of 2009 Pandemic Influenza A (H1N1) Virus Antibodies, Tampa Bay Florida — November–December, 2009

BACKGROUND: In 2009, a novel influenza virus (2009 pandemic influenza A (H1N1) virus (pH1N1)) caused significant disease in the United States. Most states, including Florida, experienced a large fall wave of disease from September through November, after which disease activity decreased substantially. We determined the prevalence of antibodies due to the pH1N1 virus in Florida after influenza activity had peaked and estimated the proportion of the population infected with pH1N1 virus during the pandemic. METHODS: During November-December 2009, we collected leftover serum from a blood bank, a pediatric children's hospital and a pediatric outpatient clinic in Tampa Bay Florida. Serum was tested for pH1N1 virus antibodies using the hemagglutination-inhibition (HI) assay. HI titers ≥40 were considered seropositive. We adjusted seroprevalence results to account for previously established HI assay specificity and sensitivity and employed a simple statistical model to estimate the proportion of seropositivity due to pH1N1 virus infection and vaccination. RESULTS: During the study time period, the overall seroprevalence in Tampa Bay, Florida was 25%, increasing to 30% after adjusting for HI assay sensitivity and specificity. We estimated that 5.9% of the population had vaccine-induced seropositivity while 25% had seropositivity secondary to pH1N1 virus infection. The highest cumulative incidence of pH1N1 virus infection was among children aged 5-17 years (53%) and young adults aged 18-24 years (47%), while adults aged ≥50 years had the lowest cumulative incidence (11-13%) of pH1N1 virus infection. CONCLUSIONS: After the peak of the fall wave of the pandemic, an estimated one quarter of the Tampa Bay population had been infected with the pH1N1 virus. Consistent with epidemiologic trends observed during the pandemic, the highest burdens of disease were among school-aged children and young adults

Intracranial Administration of P Gene siRNA Protects Mice from Lethal Chandipura Virus Encephalitis

Background: In parts of India, Chandipura Virus (CHPV) has emerged as an encephalitis causing pathogen in both epidemic and sporadic forms. This pediatric disease follows rapid course leading to 55–75 % mortality. In the absence of specific treatment, effectiveness of RNA interference (RNAi) was evaluated. Methods and Findings: Efficacy of synthetic short interfering RNA (siRNA) or short hairpin RNA (shRNA) in protecting mice from CHPV infection was assessed. The target genes were P and M genes primarily because important role of the former in viral replication and lethal nature of the latter. Real time one step RT-PCR and plaque assay were used for the assessment of gene silencing. Using pAcGFP1N1-CHPV-P, we showed that P-2 siRNA was most efficient in reducing the expression of P gene in-vitro. Both quantitative assays documented 2logs reduction in the virus titer when P-2, M-5 or M-6 siRNAs were transfected 2hr post infection (PI). Use of these siRNAs in combination did not result in enhanced efficiency. P-2 siRNA was found to tolerate four mismatches in the center. As compared to five different shRNAs, P-2 siRNA was most effective in inhibiting CHPV replication. An extended survival was noted when mice infected intracranially with 100 LD 50 CHPV were treated with cationic lipid complexed 5 mg P-2 siRNA simultaneously. Infection with 10LD 50 and treatment with two doses of siRNA first, simultaneously and second 24 hr PI, resulted in 70 % survival. Surviving mice showed 4logs less CHPV titers in brain without histopathological changes or antibody response. Gene expression profiles of P-2 siRNA treated mice showed no interferon response. First dose of siRNA at 2h

Seroepidemiology of pandemic influenza A (H1N1) 2009 virus infections in Pune, India

<p>Abstract</p> <p>Background</p> <p>In India, Pune was one of the badly affected cities during the influenza A (H1N1) 2009 pandemic. We undertook serosurveys among the risk groups and general population to determine the extent of pandemic influenza A (H1N1) 2009 virus infections.</p> <p>Methods</p> <p>Pre-pandemic sera from the archives, collected during January 2005 to March 2009, were assayed for the determination of baseline seropositivity. Serosurveys were undertaken among the risk groups such as hospital staff, general practitioners, school children and staff and general population between 15^thAugust and 11^thDecember 2009. In addition, the PCR-confirmed pandemic influenza A (H1N1) 2009 cases and their household contacts were also investigated. Haemagglutination-inhibition (HI) assays were performed using turkey red blood cells employing standard protocols. A titre of ≥1:40 was considered seropositive.</p> <p>Results</p> <p>Only 2 (0.9%) of the 222 pre-pandemic sera were positive. The test-retest reliability of HI assay in 101 sera was 98% for pandemic H1N1, 93.1% for seasonal H1N1 and 94% for seasonal H3N2. The sera from 48 (73.8%) of 65 PCR-confirmed pandemic H1N1 cases in 2009 were positive. Seropositivity among general practitioners increased from 4.9% in August to 9.4% in November and 15.1% in December. Among hospital staff, seropositivity increased from 2.8% in August to 12% in November. Seropositivity among the schools increased from 2% in August to 10.7% in September. The seropositivity among students (25%) was higher than the school staff in September. In a general population survey in October 2009, seropositivity was higher in children (9.1%) than adults (4.3%). The 15-19 years age group showed the highest seropositivity of 20.3%. Seropositivity of seasonal H3N2 (55.3%) and H1N1 (26.4%) was higher than pandemic H1N1 (5.7%) (n = 2328). In households of 74 PCR-confirmed pandemic H1N1 cases, 25.6% contacts were seropositive. Almost 90% pandemic H1N1 infections were asymptomatic or mild. Considering a titre cut off of 1:10, seropositivity was 1.5-3 times as compared to 1:40.</p> <p>Conclusions</p> <p>Pandemic influenza A (H1N1) 2009 virus infection was widespread in all sections of community. However, infection was significantly higher in school children and general practitioners. Hospital staff had the lowest infections suggesting the efficacy of infection-control measures.</p

Epidemiological Characteristics of 2009 (H1N1) Pandemic Influenza Based on Paired Sera from a Longitudinal Community Cohort Study

Steven Riley and colleagues analyze a community cohort study from the 2009 (H1N1) influenza pandemic in Hong Kong, and found that more children than adults were infected with H1N1, but children were less likely to progress to severe disease than adults

The Age-Specific Cumulative Incidence of Infection with Pandemic Influenza H1N1 2009 Was Similar in Various Countries Prior to Vaccination

Background: During the influenza pandemic of 2009 estimates of symptomatic and asymptomatic infection were needed to guide vaccination policies and inform other control measures. Serological studies are the most reliable way to measure influenza infection independent of symptoms. We reviewed all published serological studies that estimated the cumulative incidence of infection with pandemic influenza H1N1 2009 prior to the initiation of population-based vaccination against the pandemic strain. Methodology and Principal Findings: We searched for studies that estimated the cumulative incidence of pandemic influenza infection in the wider community. We excluded studies that did not include both pre- and post-pandemic serological sampling and studies that included response to vaccination. We identified 47 potentially eligible studies and included 12 of them in the review. Where there had been a significant first wave, the cumulative incidence of pandemic influenza infection was reported in the range 16%-28% in pre-school aged children, 34%-43% in school aged children and 12%-15% in young adults. Only 2%-3% of older adults were infected. The proportion of the entire population infected ranged from 11%-18%. We re-estimated the cumulative incidence to account for the small proportion of infections that may not have been detected by serology, and performed direct age-standardisation to the study population. For those countries where it could be calculated, this suggested a population cumulative incidence in the range 11%-21%. Conclusions and Significance: Around the world, the cumulative incidence of infection (which is higher than the cumulative incidence of clinical disease) was below that anticipated prior to the pandemic. Serological studies need to be routine in order to be sufficiently timely to provide support for decisions about vaccination. © 2011 Kelly et al.published_or_final_versio

Measuring the burden of arboviral diseases: the spectrum of morbidity and mortality from four prevalent infections

<p>Abstract</p> <p>Background</p> <p>Globally, arthropod-borne virus infections are increasingly common causes of severe febrile disease that can progress to long-term physical or cognitive impairment or result in early death. Because of the large populations at risk, it has been suggested that these outcomes represent a substantial health deficit not captured by current global disease burden assessments.</p> <p>Methods</p> <p>We reviewed newly available data on disease incidence and outcomes to critically evaluate the disease burden (as measured by disability-adjusted life years, or DALYs) caused by yellow fever virus (YFV), Japanese encephalitis virus (JEV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). We searched available literature and official reports on these viruses combined with the terms "outbreak(s)," "complication(s)," "disability," "quality of life," "DALY," and "QALY," focusing on reports since 2000. We screened 210 published studies, with 38 selected for inclusion. Data on average incidence, duration, age at onset, mortality, and severity of acute and chronic outcomes were used to create DALY estimates for 2005, using the approach of the current Global Burden of Disease framework.</p> <p>Results</p> <p>Given the limitations of available data, nondiscounted, unweighted DALYs attributable to YFV, JEV, CHIKV, and RVFV were estimated to fall between 300,000 and 5,000,000 for 2005. YFV was the most prevalent infection of the four viruses evaluated, although a higher proportion of the world's population lives in countries at risk for CHIKV and JEV. Early mortality and long-term, related chronic conditions provided the largest DALY components for each disease. The better known, short-term viral febrile syndromes caused by these viruses contributed relatively lower proportions of the overall DALY scores.</p> <p>Conclusions</p> <p>Limitations in health systems in endemic areas undoubtedly lead to underestimation of arbovirus incidence and related complications. However, improving diagnostics and better understanding of the late secondary results of infection now give a first approximation of the current disease burden from these widespread serious infections. Arbovirus control and prevention remains a high priority, both because of the current disease burden and the significant threat of the re-emergence of these viruses among much larger groups of susceptible populations.</p

Whole Genomes of Chandipura Virus Isolates and Comparative Analysis with Other Rhabdoviruses

The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003–2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003–2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV

Recombinant Modified Vaccinia Virus Ankara Expressing Glycoprotein E2 of Chikungunya Virus Protects AG129 Mice against Lethal Challenge

Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections