Assessment of Maternal Risk Factors for Low-Birth-Weight Neonates: A Case Control Study in Teaching Hospital

Purpose: A major factors contributing to infant deaths and morbidity is low birth weight (LBW). Low birth weight (LBW) is a significant marker for the population's general health condition and reproductive health. Maternal risk factors are controllable and vary from one region to another depending on geographic, socioeconomic, and cultural factors and are biologically, socially interrelated. Subjects and Methods: The study was conducted in a tertiary care hospital in kalaburagi. A total of 85 cases and 85 controls with normal birth weight. Mothers of aged 18-35 years who delivered a live-born singleton baby without any congenital abnormalities and gestational age 37-42 weeks were enrolled on the same day as delivery are eligible. Mothers who had multiple pregnancies were not eligible. Data was collected from Pre-tested survey. Results: The mean age of mothers in case and control group was 23.73 years and 5.04 years. Mean weight gain during pregnancy of mothers in case and control was 4.2 kg and 6.5 kg. Mean weight of the newborn of cases and controls was 2012 grams and3065 grams respectively. Maternal education, tobacco exposure, maternal anaemia, lower socioeconomic status (class IV+V), maternal occupation (laborer), heavy physical activity, pre term birth of baby, history of UTI were identified as significant risk factors for LBW neonates. Significant association was found between age of mother, height of mother<145 cm, pre pregnancy weight <45 kg, mean weight gain (<6.5kg), prior infant death, inadequate ANC visits, and LBW. Conclusions: Health education, socio-economic development, maternal nutrition, and increasing the use of health services during pregnancy, are all important for reducing LBW

Stability-indicating RP-HPLC method applied to the quantification of anti-histaminic drug ebastine in its oral suspension dosage form

For the quantification of ebastine in pharmaceutical suspension, a simple, quick, accurate, and exact stability-indicating HPLC approach was developed and validated. The drug was determined using a phase reverse system and the separation was performed in an analytical C18 column (250 mm x 4.6 mm, 5 μm). The mobile phase consists of 0.1% orthophosphoric acid and methanol in a 25:75, v/v ratio. Using a concentration range of 10–90 μg mL-1, the technique demonstrated a strong linear response (r=0.999). Effluents were measured at 262 nm while the flow rate was kept at 1.0 mL min-1. There was a retention time of 3.506 min. The method was statistically validated to determine its accuracy, precision, linearity, ruggedness, robustness, solution stability, selectivity, and forced degradation assessments. The stresses that were used were acid, alkali hydrolysis, water stress, oxidation, photolysis, and heat. Since the degradation products did not affect the capacity to identify ebastine, this technique may be taken as a stability indication. This methodology may be utilized for the analysis of Ebastine in pharmaceutical suspension, since the findings obtained were within the limits set by ICH standards

Stability of different mesoporous silica particles during an in vitro digestion

Mesoporous silica materials have the ability to entrap drugs, nutrients and functional biomolecules and can be able to act as smart delivery systems capable to control and target the release of their cargo in a particular part of the gastrointestinal tract when administrated orally. However, the aptness of these encapsulation supports in in vivo oral controlled release relies on their chemical stability through the digestive tube. In this context, we have evaluated the stability of four different mesoporous silica particles, frequently used as encapsulating supports, during an in vitro digestion process comprising buccal, stomach and intestinal phases. Results showed that after 4 h of digestion, the textural properties of silica supports in the form of nanoparticles (MCM-41 and UVM-7 nanoparticles) were lost in varying degrees, whereas silica microparticles supports (MCM-41 and SBA-15 microparticles) endures better the digestion process. Moreover, the functionalization of the surface with N-1-(3-trimethoxysilylpropyl)diethylenetriamine, an organic moiety commonly used in the preparation of pH-responsive mesoporous silica particles, resulted in an improvement of the stability of the supports. (C) 2016 Elsevier Inc. All rights reserved.Authors gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad (Projects AGL2012-39597-C02-01, AGL2012-39597-C02-02 and MAT2012-38429-C04-01 and MAT2012-38429-C04-03), Generalitat Valenciana (project PROMETEO/2009/016) and FEDER founding. E.P. and M.R are grateful to the Ministerio de Ciencia e Innovacion for their grants (AP2008-00620, AP2010-4369). Electron Microscopy Service of the UPV is also acknowledged.Pérez-Esteve, É.; Ruiz Rico, M.; Torre, CDL.; Llorca Martínez, ME.; Sancenón Galarza, F.; Marcos Martínez, MD.; Amoros Del Toro, PJ.... (2016). Stability of different mesoporous silica particles during an in vitro digestion. Microporous and Mesoporous Materials. 230:196-207. https://doi.org/10.1016/j.micromeso.2016.05.004S19620723

Towards sustainable polymeric nano-carriers and surfactants: facile low temperature enzymatic synthesis of bio-based amphiphilic copolymers in scCO2

We demonstrate that useful bio-based amphiphilic polymers can be produced enzymatically at a mild temperature, in a solvent-free system and using renewably sourced monomers, by exploiting the unique properties of supercritical CO2 (scCO2). We present the use of a novel near-ambient temperature approach to prepare renewable amphiphilic ABA copolymers in scCO2. Bio-based commercially available monomers have been polymerised to prepare chains with targeted molecular weight. The amphiphilic materials were prepared by end-capping the synthesised polymers with methoxy poly(ethylene glycol) (MPEG) chains in a one-pot high pressure reaction utilising Candida Antarctica Lipase B (CaLB) as a catalyst at a temperature as low as 35 °C. The block copolymers are characterised by 1H-NMR, GPC and DSC in order to carefully assess their structural and thermal properties. These polymers form self-assembled aggregates in aqueous environment and these nanostructures are studied through DLS, TEM and UV-Vis. Highly hydrophobic Coumarin-6 was used as a model to prove dispersion in water of lipophilic molecules. Maximum bubble pressure tests demonstrate the reduction in surface tension of these polymers and comparisons are made directly to commercial polymeric non-ionic surfactants

Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial

Background: Infants are a key target population for new tuberculosis vaccines. We assessed the safety and immunogenicity of the live-attenuated Mycobacterium tuberculosis vaccine candidate MTBVAC in adults and infants in a region where transmission of tuberculosis is very high. Methods: We did a randomised, double-blind, BCG-controlled, dose-escalation trial at the South African Tuberculosis Vaccine Initiative site near Cape Town, South Africa. Healthy adult community volunteers who were aged 18–50 years, had received BCG vaccination as infants, were HIV negative, had negative interferon-¿ release assay (IGRA) results, and had no personal history of tuberculosis or current household contact with someone with tuberculosis were enrolled in a safety cohort. Infants born to HIV-negative women with no personal history of tuberculosis or current household contact with a person with tuberculosis and who were 96 h old or younger, generally healthy, and had not yet received routine BCG vaccination were enrolled in a separate infant cohort. Eligible adults were randomly assigned (1:1) to receive either BCG Vaccine SSI (5 × 105 colony forming units [CFU] of Danish strain 1331 in 0·1 mL diluent) or MTBVAC (5 × 105 CFU in 0·1 mL) intradermally in the deltoid region of the arm. After favourable review of 28-day reactogenicity and safety data in the adult cohort, infants were randomly assigned (1:3) to receive either BCG Vaccine SSI (2·5 × 105 CFU in 0·05 mL diluent) or MTBVAC in three sequential cohorts of increasing MTBVAC dose (2·5 × 103 CFU, 2·5 × 104 CFU, and 2·5 × 105 CFU in 0·05 mL) intradermally in the deltoid region of the arm. QuantiFERON-TB Gold In-Tube IGRA was done on days 180 and 360. For both randomisations, a pre-prepared block randomisation schedule was used. Participants (and their parents or guardians in the case of infant participants), investigators, and other clinical and laboratory staff were masked to intervention allocation. The primary outcomes, which were all measured in the infant cohort, were solicited and unsolicited local adverse events and serious adverse events until day 360; non-serious systemic adverse events until day 28 and vaccine-specific CD4 and CD8 T-cell responses on days 7, 28, 70, 180, and 360. Secondary outcomes measured in adults were local injection-site and systemic reactions and haematology and biochemistry at study day 7 and 28. Safety analyses and immunogenicity analyses were done in all participants who received a dose of vaccine. This trial is registered with ClinicalTrials.gov, number NCT02729571. Findings: Between Sept 29, 2015, and Nov 16, 2015, 62 adults were screened and 18 were enrolled and randomly assigned, nine each to the BCG and MTBVAC groups. Between Feb 12, 2016, and Sept 21, 2016, 36 infants were randomly assigned—eight to the BCG group, nine to the 2·5 × 103 CFU MTBVAC group, nine to the 2·5 × 104 CFU group, and ten to the 2·5 × 105 CFU group. Mild injection-site reactions occurred only in infants in the BCG and the 2·5 × 105 CFU MTBVAC group, with no evidence of local or regional injection-site complications. Systemic adverse events were evenly distributed across BCG and MTBVAC dose groups, and were mostly mild in severity. Eight serious adverse events were reported in seven vaccine recipients (one adult MTBVAC recipient, one infant BCG recipient, one infant in the 2·5 × 103 CFU MTBVAC group, two in the 2·5 × 104 CFU MTBVAC group, and two in the 2·5 × 105 CFU MTBVAC group), including one infant in the 2·5 × 103 CFU MTBVAC group treated for unconfirmed tuberculosis and one in the 2·5 × 105 CFU MTBVAC group treated for unlikely tuberculosis. One infant died as a result of possible viral pneumonia. Vaccination with all MTBVAC doses induced durable antigen-specific T-helper-1 cytokine-expressing CD4 cell responses in infants that peaked 70 days after vaccination and were detectable 360 days after vaccination. For the highest MTBVAC dose (ie, 2·5 × 105 CFU), these responses exceeded responses induced by an equivalent dose of the BCG vaccine up to 360 days after vaccination. Dose-related IGRA conversion was noted in three (38%) of eight infants in the 2·5 × 103 CFU MTBVAC group, six (75%) of eight in the 2·5 × 104 CFU MTBVAC group, and seven (78%) of nine in the 2·5 × 105 CFU MTBVAC group at day 180, compared with none of seven infants in the BCG group. By day 360, IGRA reversion had occurred in all three infants (100%) in the 2·5 × 103 CFU MTBVAC group, four (67%) of the six in the 2·5 × 104 CFU MTBVAC group, and three (43%) of the seven in the 2·5 × 105 CFU MTBVAC group. Interpretation: MTBVAC had acceptable reactogenicity, and induced a durable CD4 cell response in infants. The evidence of immunogenicity supports progression of MTBVAC into larger safety and efficacy trials, but also confounds interpretation of tests for M tuberculosis infection, highlighting the need for stringent endpoint definition. Funding: Norwegian Agency for Development Cooperation, TuBerculosis Vaccine Initiative, UK Department for International Development, and Biofabri

Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, Combretastatin A4

The hydrophobicity of a drug can be a major challenge in its development and prevents the clinical translation of highly potent anti-cancer agents. We have used a lipid-based nanoemulsion termed Lipid-Oil-Nanodroplets (LONDs) for the encapsulation and in vivo delivery of the poorly bioavailable combretastatin A4 (CA4). Drug delivery with CA4 LONDs was assessed in a xenograft model of colorectal cancer. LC–MS/MS analysis revealed that CA4 LONDs, administered at a drug dose four times lower than drug control, achieved equivalent concentrations of CA4 intratumorally. We then attached CA4 LONDs to microbubbles (MBs) and targeted this construct to VEGFR2. A reduction in tumor perfusion was observed in CA4 LONDs-MBs treated tumors. A combination study with irinotecan demonstrated a greater reduction in tumor growth and perfusion (P = 0.01) compared to irinotecan alone. This study suggests that LONDs, either alone or attached to targeted MBs, have the potential to significantly enhance tumor-specific hydrophobic drug delivery

Tailored Approaches in Drug Development and Diagnostics: From Molecular Design to Biological Model Systems

Approaches to increase the efficiency in developing drugs and diagnostics tools, including new drug delivery and diagnostic technologies, are needed for improved diagnosis and treatment of major diseases and health problems such as cancer, inflammatory diseases, chronic wounds, and antibiotic resistance. Development within several areas of research ranging from computational sciences, material sciences, bioengineering to biomedical sciences and bioimaging is needed to realize innovative drug development and diagnostic (DDD) approaches. Here, an overview of recent progresses within key areas that can provide customizable solutions to improve processes and the approaches taken within DDD is provided. Due to the broadness of the area, unfortunately all relevant aspects such as pharmacokinetics of bioactive molecules and delivery systems cannot be covered. Tailored approaches within (i) bioinformatics and computer-aided drug design, (ii) nanotechnology, (iii) novel materials and technologies for drug delivery and diagnostic systems, and (iv) disease models to predict safety and efficacy of medicines under development are focused on. Current developments and challenges ahead are discussed. The broad scope reflects the multidisciplinary nature of the field of DDD and aims to highlight the convergence of biological, pharmaceutical, and medical disciplines needed to meet the societal challenges of the 21st century