Characterization of bilayered matrix-type mucoadhesive buccal films containing tizanidine hydrochloride and piroxicam

Purpose: To formulate and characterize tizanidine hydrochloride (TZN) and piroxicam (PRX)-loaded bilayer mucoadhesive buccal films with an intention to improve the bioavailability and patient compliance in pain management.Methods: Bilayer buccal films were prepared by solvent evaporation technique using hydroxypropyl methylcellulose (HPMC) 15cps and polyvinylpyrrolidone (PVP K30 as immediate release (IR) layer forming polymers and HPMC K15 M, PVP K 90 along with various muco adhesive polymers (Carbopol P934, sodium alginate, etc), as sustained release (SR) layer forming polymers. The prepared films werecharacterized for thickness, weight variation, folding endurance, surface pH, swelling index,mucoadhesive strength, in vitro residence time, in vitro drug release, ex vivo permeation and drug release kinetics.Results: The prepared films were of largely uniform thickness, weight and drug content. Moisture loss (%) and folding endurance were satisfactory. Surface pH was compatible with salivary fluid. Disintegration time was 85 s for F1 and 115 s for F2 of IR films. In vitro dissolution studies showed 99.12 ± 1.2 % (F1) and 90.36 ± 1.8 % (F2) were released in 45 min. Based on the above results, F1 was chosen as the optimum formulation to be combined with SR layer of TZN. Amongst the SR layers of TZN in vitro drug release. The findings show that of F2 was 98.38 ± 0.82 % and correlated with ex vivo release. Drug release followed zero order release kinetics and mechanism of drug release was non-Fickian type diffusion. In vitro residence time was greater than 5 h.Conclusion: The findings show that the bilayer buccal films demonstrate the dual impact of deliveringPRX instantly from the IR layer, with good controlled release and permeation of TZN from the SR layer, thus providing enhanced therapeutic efficacy, drug bioavailability and patient compliance

FORMULATION AND EVALUATION OF DASATINIB LOADED SOLID LIPID NANOPARTICLES

Objective: The aim of present work was to formulate and evaluate Dasatinib (DST) loaded solid lipid nanoparticles (SLNs) as a potential anticancer drug delivery system by enhancing its solubility.Methods: SLNs consist of a solid lipid matrix where the drug was incorporated. Surfactants of GRAS grade were used to avoid aggregation and to stabilize the SLNs. DST-SLNs formulations of varying concentrations were prepared by high speed homogenization technique and evaluated for drug excipients compatibility study, poly-dispersity index, particle size analysis, surface morphology, zeta potential and drug release features.Results: It was observed that DST-SLNs with optimum quantities of poloxomer: lecithin ratio showed 88.06% drug release in 6h with good entrapment efficiency of 76.9±0.84 %. Particle size, Poly dispersity index, zeta potential and drug entrapment efficiency for the optimized formulation was found to be optimum. Stability studies revealed that the entrapment efficiency of the SLN dispersion stored in 4 °C was stable.Conclusion: Thus, it can be concluded that formulations of DST loaded SLNs are suitable carriers for improving the solubility and dissolution related problems.Â

Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions

Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens

Clostridium Difficile Associated Diarrhea in Children with Hematological Malignancy-Experience from a Pediatric Oncologic Centre, Bangladesh

Background: Clostridium difficile Associated Diarrhea (CDAD) is considered to be one of the commonest causes of nosocomial diarrhoea worldwide. Gastrointestinal infections in the form of diarrhoea are common in pediatric oncology patients in Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh. The study was conducted to find out the frequency of Clostridium difficile infection (CDI) among diarrheal children with haematological malignancy. Materials and Methods: This prospective observational study was conducted from April 2012 to March 2013 at the Pediatric Hematology and Oncology Unit, BSMMU, Bangladesh. Total 58 diarrheal episodes occurred in 51 children with various types of haematological malignancies were included consecutively. Faecal samples of the children were sent to International Centre for Diarrheal Disease Research, Bangladesh (ICDDR, B) laboratory for detection of Clostridium difficile antigen (GDH) and toxins (A and/ or B) by Enzyme Immunoassay (EIA). Results: Among 58 diarrheal episodes 22.4% faecal samples were positive for GDH, but none of the faecal samples was positive for toxin A and or B. There were a significant association with leucopenia, severe neutropenia; usage of meropenem plus vancomycin, cefepime plus amikacin, imipenem, cytarabine and omeprazole with GDH positive diarrheal episodes. Conclusion: Positive GDH antigen with a negative result for toxin indicates C. difficile colonization. Among GDH positive episodes, a significantly higher proportion of children had leucopenia, severe neutropenia and usage of some drugs known as risk factors for C. difficile infection. To confirm the CDI advanced tests are needed

Community participation in health, family planning and development activities: A review of international experiences

The family planning (FP)/maternal and child health (MCH) program in Bangladesh has achieved success in the recent past, mostly through a large-scale government service-delivery system with support and cooperation from donors and nongovernmental organizations. There is concern about the financial and social sustainability of the program. Other issues include achievement of replacement-level fertility within a stipulated period and improvement of MCH-FP service quality. It is widely believed that most of the concerns will be taken care of with effective community participation. Before activating community initiatives, it is worth carrying out action research. A literature review was completed from July to October 1996 to identify a range of models used for increasing community participation and experiences in terms of implementation, management, financing, monitoring and evaluation, and sustainability in both rural and urban areas. Attempts were also made to identify a set of indicators to assess the level of community participation in these programs. This report documents the results of the review

Hydroponic and in vitro screening of wheat varieties for salt-tolerance

Salt-tolerant wheat cultivars are essential for sustainable wheat production and global food security. The present study aimed to establish a reliable screening protocol as well as successfully isolated the potential salt-tolerant wheat varieties by discerning morpho-physiological parameters with multivariate analysis. Seventeen wheat varieties were evaluated at 0, 12, 15 and 18 dSm-1 salinity levels in a hydroponic culture system at the seedling stage. Moreover, in vitro callusing responses of four selected varieties were determined to clarify the salt tolerance capability at 0, 9, 12 and 15 dSm-1 salt treatments. The seedling growth of most wheat varieties was highly interrupted and reduced by the toxic effects of salinity, however, some varieties such as BARI Gom-32, BARI Gom-33, BARI Gom-31, BARI Gom-30, and BARI Gom-28 showed the lowest reduction under all salinity stress conditions. The total salt tolerance index (TSTI) showed that the cultivar BARI Gom-33 was the most salt-tolerant followed by BARI Gom-32 and BARI Gom-30 whereas BARI Gom-25 was identified as the most sensitive. These results were strongly supported by the principal component analysis (PCA) and Ward’s Methods Euclidean based clustering. In vitro results revealed that the lowest reduction of callus induction was recorded in BARI Gom-33 which might show the greatest tolerance to salinity by improving morpho-physiological characteristics against salt stress. Therefore, the identified genotypes might be employed as donor parents to develop salt-tolerant and high-yielding cultivars in the wheat breeding programme

Resistance pattern and molecular characterization of enterotoxigenic Escherichia coli (ETEC) strains isolated in Bangladesh

Enterotoxigenic Escherichia coli (ETEC) is a common cause of bacterial infection leading to acute watery diarrhea in infants and young children as well as in travellers to ETEC endemic countries. Ciprofloxacin is a broad-spectrum antimicrobial agent nowadays used for the treatment of diarrhea. This study aimed to characterize ciprofloxacin resistant ETEC strains isolated from diarrheal patients in Bangladesh.A total of 8580 stool specimens from diarrheal patients attending the icddr,b Dhaka hospital was screened for ETEC between 2005 and 2009. PCR and Ganglioside GM1- Enzyme Linked Immuno sorbent Assay (ELISA) was used for detection of Heat labile (LT) and Heat stable (ST) toxins of ETEC. Antimicrobial susceptibilities for commonly used antibiotics and the minimum inhibitory concentration (MIC) of nalidixic acid, ciprofloxacin and azithromycin were examined. DNA sequencing of representative ciprofloxacin resistant strains was performed to analyze mutations of the quinolone resistance-determining region of gyrA, gyrB, parC and parE. PCR was used for the detection of qnr, a plasmid mediated ciprofloxacin resistance gene. Clonal variations among ciprofloxacin resistant (CipR) and ciprofloxacin susceptible (CipS) strains were determined by Pulsed-field gel electrophoresis (PFGE).Among 1067 (12%) ETEC isolates identified, 42% produced LT/ST, 28% ST and 30% LT alone. Forty nine percent (n = 523) of the ETEC strains expressed one or more of the 13 tested colonization factors (CFs) as determined by dot blot immunoassay. Antibiotic resistance of the ETEC strains was observed as follows: ampicillin 66%, azithromycin 27%, ciprofloxacin 27%, ceftriazone 13%, cotrimaxazole 46%, doxycycline 44%, erythromycin 96%, nalidixic acid 83%, norfloxacin 27%, streptomycin 48% and tetracycline 42%. Resistance to ciprofloxacin increased from 13% in 2005 to 34% in 2009. None of the strains was resistant to mecillinam. The MIC of the nalidixic acid and ciprofloxacin of representative CipR strains were 256 μg/ml and 32μg/ml respectively. A single mutation (Ser83-Leu) in gyrA was observed in the nalidixic acid resistant ETEC strains. In contrast, double mutation in gyrA (Ser83-Leu, Asp87-Asn) and a single mutation in parC (Glu84-Ly) were found in ciprofloxacin resistant strains. Mutation of gyrB was not found in either the nalidixic acid or ciprofloxacin resistant strains. None of the ciprofloxacin resistant strains was found to be positive for the qnr gene. Diverse clones were identified from all ciprofloxacin resistant strains by PFGE analysis in both CF positive and CF negative ETEC strains.Emergence of ciprofloxacin resistant ETEC strains results in a major challenge in current treatment strategies of ETEC diarrhea

ETHNOMEDICINES OF HIGHLY UTILIZED PLANTS IN THE TEMPERATE HIMALAYAN REGION

Background: Himalayan region of Pakistan has been known as a rich source for valuable medicinal plants. The present work is the documentation of indigenous knowledge of highly utilized plants as natural remedy by the local inhabitants of the northwest part of the country. Methodology: Data on highly utilized medicinal plants were collected during May-September 2012 using semi-structured questionnaire from the elders, local herbalists and medicinal plants collectors. Results: In total about 53, plants belonging to 38, families were highly utilized in the study area, of which majority of those (43), were medicinal plants. The most frequent part used in preparation of different medicinal remedies is leaves (53%). Most of the medicinal plant species (14) were used as antipyretic. The inhabitants of the study area were producing ethno-medicines mostly in crushed form (26%). Most of the remedies (74%), were taken orally within the study area. Ten species were found most valuable from the local’s perspective such as Bergenia ciliata, Hedera nepalensis and Viola canescens. Conclusion: In conclusion, traditional healers depend largely on naturally growing medicinal plant species, which are under severe threat. This study can provide a basis for further phyto-chemical and pharmacological studies on the region’s medicinal plants. Moreover, documentation of indigenous recipes would serve as preservation of the knowledge for the generations to come

Examination of the enterotoxigenic Escherichia coli population structure during human infection

Enterotoxigenic E. coli (ETEC) can cause severe diarrhea and death in children in developing countries; however, bacterial diversity in natural infection is uncharacterized. In this study, we explored the natural population variation of ETEC from individuals with cholera-like diarrhea. Genomic sequencing and comparative analysis of multiple ETEC isolates from twelve cases of severe diarrhea demonstrated clonal populations in the majority of subjects (10/12). In contrast, a minority of individuals (2/12) yielded phylogenomically divergent ETEC isolates. Detailed examination revealed that isolates also differed in virulence factor content. These genomic data suggest that severe, cholera-like ETEC infections are largely caused by a clonal population of organisms within individual patients. Additionally, the isolation of similar clones from geographically and temporally dispersed cases with similar clinical presentations suggests that some isolates are particularly suited for virulence. The identification of multiple genomically diverse isolates with variable virulence factor profiles from a single subject highlights the dynamic nature of ETEC, as well as a potential weakness in the examination of cultures obtained from a single colony in clinical settings. These findings have implications for vaccine design and provide a framework for the study of population variation in other human pathogens

Enterotoxigenic Escherichia coli and Vibrio cholerae Diarrhea, Bangladesh, 2004

Flooding in Dhaka in July 2004 caused epidemics of diarrhea. Enterotoxigenic Escherichia coli (ETEC) was almost as prevalent as Vibrio cholerae O1 in diarrheal stools. ETEC that produced heat-stable enterotoxin alone was most prevalent, and 78% of strains had colonization factors. Like V. cholerae O1, ETEC can cause epidemic diarrhea