DEVELOPMENT OF MUCOADHESIVE CARBOHYDRATE HETEROPOLYMER MICROBEADS FOR SUSTAIN RELEASE OF THEOPHYLLINE

Objective: The aim of present study was to develop and evaluate mucoadhesive microbeads for oral sustained release of an antiasthmatic agent theophylline†using natural gums such as sodium alginate and sesbania gum.Methods: The compatibility studies of drug with different polymers were investigated by using DSC (Differential Scanning Calorimeter) and FTIR (Fourier Transform Infrared Spectroscopy). Carbohydrate heteropolymer microbeads of alginate and sesbania gums were prepared by ionotropic gelation technique, where calcium chloride is used as a source of counter ions. Prepared beads were characterized for particle size, entrapment efficiency, surface morphology, swelling index, in vitro release studies and release kinetics.Results: Final optimized formulation consists of a polymer blend of alginate and sesbania gum with hydroxy propyl cellulose as release modifier. Microbeads exhibited good swelling index and high percentage of drug entrapment efficiency. The developed formulation showed a maximum drug release of 92% in 11 h using 0.1 N hydrochloric acid buffer (pH 1.2). The formulation followed Korsmeyer-Peppas and Higuchi release mechanism, releasing the drug by non-fickian diffusion. Prepared beads showed significant mucoadhesion in acidic buffer.Conclusion: The sustained release microbeads were successfully designed for oral administration of theophylline which may be used for the treatment of nocturnal asthma.Â

Candida tropicalis endocarditis successfully treated with AngioVac and micafungin followed by long-term isavuconazole suppression

We provide a review of current literature of native valve Candida tropicalis endocarditis. A 41-year old man presented with C. tropicalis candidemia complicated by superior vena cava mass and right main pulmonary artery thrombus. The patient achieved clinical and microbiologic cure with AngioVac of the mass and echinocandin for six weeks. Long-term suppression was challenging given the C. tropicalis strain was resistant to fluconazole, voriconazole and posaconazole. Additional susceptibilities were obtained and he remained relapse-free at 12 months with isavuconazole

Standardizing Scavenger Receptor Nomenclature

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a variety of ligands, including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the U.S. National Institute of Allergy and Infectious Diseases, National Institutes of Health to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of non-self or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. The discussion and nomenclature recommendations described in this report only refer to mammalian scavenger receptors. The purpose of this article is to describe the proposed mammalian nomenclature and classification developed at the workshop and to solicit additional feedback from the broader research community

A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by theUnited StatesNational Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of nonself or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. This classification was discussed at three national meetings and input from participants at these meetings was requested. The following manuscript is a consensus statement that combines the recommendations of the initial workshop and incorporates the input received from the participants at the three national meetings

Cysteamine Suppresses Invasion, Metastasis and Prolongs Survival by Inhibiting Matrix Metalloproteinases in a Mouse Model of Human Pancreatic Cancer

Background: Cysteamine, an anti-oxidant aminothiol, is the treatment of choice for nephropathic cystinosis, a rare lysosomal storage disease. Cysteamine is a chemo-sensitization and radioprotection agent and its antitumor effects have been investigated in various tumor cell lines and chemical induced carcinogenesis. Here, we investigated whether cysteamine has anti-tumor and anti-metastatic effects in transplantable human pancreatic cancer, an aggressive metastatic disease. Methodology/Principal Findings: Cysteamine’s anti-invasion effects were studied by matrigel invasion and cell migration assays in 10 pancreatic cancer cell lines. To study mechanism of action, we examined cell viability and matrix metalloproteinases (MMPs) activity in the cysteamine-treated cells. We also examined cysteamine’s anti-metastasis effect in two orthotopic murine models of human pancreatic cancer by measuring peritoneal metastasis and survival of animals. Cysteamine inhibited both migration and invasion of all ten pancreatic cancer cell lines at concentrations (,25 mM) that caused no toxicity to cells. It significantly decreased MMPs activity (IC50 38–460 mM) and zymographic gelatinase activity in a dose dependent manner in vitro and in vivo; while mRNA and protein levels of MMP-9, MMP-12 and MMP-14 were slightly increased using the highest cysteamine concentration. In vivo, cysteamine significantly decreased metastasis in two established pancreatic tumor models, although it did not affect the size of primary tumors. Additionally, cysteamin

Systemic Stimulation of TLR2 Impairs Neonatal Mouse Brain Development

Background: Inflammation is associated with perinatal brain injury but the underlying mechanisms are not completely characterized. Stimulation of Toll-like receptors (TLRs) through specific agonists induces inflammatory responses that trigger both innate and adaptive immune responses. The impact of engagement of TLR2 signaling pathways on the neonatal brain is still unclear. The aim of this study was to investigate the potential effect of a TLR2 agonist on neonatal brain development. Methodology/Principal Findings: Mice were injected intraperitoneally (i.p.) once a day from postnatal day (PND) 3 to PND11 with endotoxin-free saline, a TLR2 agonist Pam$_{3}$CSK$_{4}$ (5 mg/kg) or Lipopolysaccharide (LPS, 0.3 mg/kg). Pups were sacrificed at PND12 or PND53 and brain, spleen and liver were collected and weighed. Brain sections were stained for brain injury markers. Long-term effects on memory function were assessed using the Trace Fear Conditioning test at PND50. After 9 days of Pam$_{3}$CSK$_{4}$ administration, we found a decreased volume of cerebral gray matter, white matter in the forebrain and cerebellar molecular layer that was accompanied by an increase in spleen and liver weight at PND12. Such effects were not observed in Pam$_{3}$CSK$_{4}$-treated TLR 2-deficient mice. Pam$_{3}$CSK$_{4}$-treated mice also displayed decreased hippocampus neuronal density, and increased cerebral microglia density, while there was no effect on caspase-3 or general cell proliferation at PND12. Significantly elevated levels of IL-1β, IL-6, KC, and MCP-1 were detected after the first Pam$_{3}$CSK$_{4}$ injection in brain homogenates of PND3 mice. Pam$_{3}$CSK$_{4}$administration did not affect long-term memory function nor the volume of gray or white matter. Conclusions/Significance: Repeated systemic exposure to the TLR2 agonist Pam$_{3}$CSK$_{4}$ can have a short-term negative impact on the neonatal mouse brain

Nucleoprotein Nanostructures Combined with Adjuvants Adapted to the Neonatal Immune Context: A Candidate Mucosal RSV Vaccine

BACKGROUND: The human respiratory syncytial virus (hRSV) is the leading cause of severe bronchiolitis in infants worldwide. The most severe RSV diseases occur between 2 and 6 months-of-age, so pediatric vaccination will have to be started within the first weeks after birth, when the immune system is prone to Th2 responses that may turn deleterious upon exposure to the virus. So far, the high risk to prime for immunopathological responses in infants has hampered the development of vaccine. In the present study we investigated the safety and efficacy of ring-nanostructures formed by the recombinant nucleoprotein N of hRSV (N(SRS)) as a mucosal vaccine candidate against RSV in BALB/c neonates, which are highly sensitive to immunopathological Th2 imprinting. METHODOLOGY AND PRINCIPAL FINDINGS: A single intranasal administration of N(SRS) with detoxified E. coli enterotoxin LT(R192G) to 5-7 day old neonates provided a significant reduction of the viral load after an RSV challenge at five weeks of age. However, neonatal vaccination also generated an enhanced lung infiltration by neutrophils and eosinophils following the RSV challenge. Analysis of antibody subclasses and cytokines produced after an RSV challenge or a boost administration of the vaccine suggested that neonatal vaccination induced a Th2 biased local immune memory. This Th2 bias and the eosinophilic reaction could be prevented by adding CpG to the vaccine formulation, which, however did not prevent pulmonary inflammation and neutrophil infiltration upon viral challenge. CONCLUSIONS/SIGNIFICANCE: In conclusion, protective vaccination against RSV can be achieved in neonates but requires an appropriate combination of adjuvants to prevent harmful Th2 imprinting

De novo assembly of transcriptome and draft chloroplast genome from RNAseq data of Bacopa monnieri L. (Bramhi)

Medicinal plant naming services have recorded at least 28,187 plant species as being of medicinal use. Only 16% (4,478) of these plants have been cited in medicinal regulatory publications and even a lesser proportion of it has ready-to-use transcript sequence information available in public data bases. Bacopa monnieri L. or Bramhi is a widely used medicinal herb mentioned in ancient ayurvedic scripts as a part of medhya rasayanas (brain rejuvenating neutraceuticals). In spite of being an extensively studied plant, it has very little genetic resources in pubic databases, thereby limiting extensive molecular studies based on genetics. In this study we sequenced the whole transcriptome of B. monnieri L. using Illumina Hiseq 2500 producing ~78 million high quality reads, followed by the de novo assembly generating a transcriptome size of ~88Mb and 111,290 clustered unigene transcripts. Plant non-redundant database, pfam and uniprot database were used as reference databases and a total of 59,260 (53.25%) transcripts were annotated based on similarity searches. Pathway mapping of the unigenes using Kyoto encyclopedia of genes and genomes revealed 14,816 transcripts involved in 143 pathways. The triterpenoid and sesquiterpenoid biosynthesis pathway was selected to validate the assembled transcripts as the bioactive compounds in B. monnieri L. are reported to be triterpenoids. Simple sequence repeat (SSR) analysis excluding mono-nucleotide repeats showed the presence of 10,556 SSR's in a total of 8892 transcripts. An attempt was made to assemble the draft chloroplast genome from the assembled transcriptome data and ~65% of chloroplast genome has been assembled and in progress. The draft chloroplast genome will also help in shedding light towards the evolution of B. monnieri L. The current study will provide information about key enzymes involved in various biosynthetic pathways and also a resource for comparative genomic and transcriptomic studies in future

Brucellosis in high risk group individuals

Purpose: The purpose of this study was to investigate the seroprevalence of brucellosis among high-risk group individuals, consisting of veterinarians and para-veterinarians, shepherds, butchers and animal owners. Methods: The present work was carried out at Project Directorate on Animal Disease Monitoring and Surveillance, Bangalore, by using the recently developed indirect enzyme-linked immunosorbent assay (ELISA) for antibodies to Brucella abortus . Results: The results were compared with the conventional serological tests, Rose Bengal plate test and standard tube agglutination test. The result showed that the indirect ELISA was more sensitive than the conventional tests. Of 618 tested, the disease of prevalence was at 41.23% in veterinary inspectors, 30.92% in veterinary assistants, 12.37% in veterinary officers, 6.18% in veterinary supervisors, 6.18% in Group D workers, 2.06% in shepherds and 1.03% in butchers. Conclusions: This study results highlight the immediate necessity to institute control measures to control Brucellosis