Studies on the role of goat heart galectin-1 as an erythrocyte membrane perturbing agent

AbstractGalectins are β-galactoside binding lectins with a potential hemolytic role on erythrocyte membrane integrity and permeability. In the present study, goat heart galectin-1 (GHG-1) was purified and investigated for its hemolytic actions on erythrocyte membrane. When exposed to various saccharides, lactose and sucrose provided maximum protection against hemolysis, while glucose and galactose provided lesser protection against hemolysis. GHG-1 agglutinated erythrocytes were found to be significantly hemolyzed in comparison with unagglutinated erythrocytes. A concentration dependent rise in the hemolysis of trypsinized rabbit erythrocytes was observed in the presence of GHG-1. Similarly, a temperature dependent gradual increase in percent hemolysis was observed in GHG-1 agglutinated erythrocytes as compared to negligible hemolysis in unagglutinated cells. The hemolysis of GHG-1 treated erythrocytes showed a sharp rise with the increasing pH up to 7.5 which became constant till pH 9.5. The extent of erythrocyte hemolysis increased with the increase in the incubation period, with maximum hemolysis after 5h of incubation. The results of this study establish the ability of galectins as a potential hemolytic agent of erythrocyte membrane, which in turn opens an interesting avenue in the field of proteomics and glycobiology

Synthesis of 2-{[5-(aralkyl/aryl)-1,3,4-oxadiazol-2- yl]sulfanyl}-N-(4-methyl-1,3-thiazol-2-yl)acetamides: Novel bi-heterocycles as potential therapeutic agents

Purpose: To evaluate the therapeutic potential of new bi-heterocycles  containing a 1,3-thiazole and 1,3,4-oxadiazole in the skeleton against Alzheimer's disease and diabetes, supported by in-silico study. Methods: The synthesis was initiated by the reaction of 4-methyl- 1,3-thiazol-2-amine (1) with bromoacetyl bromide (2) in aqueous basic medium to obtain an electrophile,2-bromo-N-(4-methyl-1,3- thiazol- 2-yl)acetamide (3). In parallel reactions, a series of carboxylic acids, 4a-r, were converted through a sequence of three steps, into respective 1,3,4-oxadiazole heterocyclic cores, 7a-r, to utilize as nucleophiles. Finally, the designed molecules, 8a-r, were synthesized by coupling 7a-r individually with 3 in an aprotic polar solvent. The structures of these bi-heterocycles were elucidated by infrared (IR), electron ionization-mass spectrometry (EI-MS), proton nuclear magnetic resonance (1H-NMR) and carbon nuclear magnetic resonance (13C-NMR). To evaluate their enzyme inhibitory potential, 8a-r were screened against acetylcholinesterase (AChE), but brine shrimp lethality bioassay.Results: The most active compound against AChE was 8l with half-maximal inhibitory concentration (IC50) of 17.25 ± 0.07 μM. Against BChE, the highest inhibitory effect was shown by 8k (56.23 ± 0.09 μM). Compound 8f (161.26 ± 0.23μM) was recognized as a fairly good inhibitor of urease. In view of its inhibition of α-glucosidase, 8o (57.35 ± 0.17μM) was considered a potential therapeutic agent.Conclusion: The results indicate that some of the synthesized products with low toxicity exhibit notable enzyme inhibitory activity against selected enzymes compared with the reference drug, and therefore, are of potential therapeutic interestKeywords: 4-Methyl-1,3-thiazol-2-amine,1,3,4-Oxadiazole,  Cholinesterases, α-Glucosidase, Urease, Brine shrim

Synthesis, Characterization, Antibacterial, α-Glucosidase Inhibition and Hemolytic Studies on Some New N-(2,3- Dimethylphenyl)benzenesulfonamide Derivatives

Purpose: To synthesize a series of new N-(2,3-dimethylphenyl)benzenesulfonamide derivatives with pharmacological analysis.Methods: N-(2,3-Dimethylphenyl)benzenesulfonamide (3) was synthesized by the reaction between 2,3-dimethylaniline (1) and benzenesulfonyl chloride (2) in aqueous basic medium. Compound 3 was further treated with various alkyl/aralakyl halides (4a-m) to yield new compounds, 5a-m, in a weak basic aprotic polar organic medium. The proposed structures of synthesized compounds were confirmed using proton-nuclear magnetic resonance (1H-NMR), infra red spectroscopy (IR) and electron impact mass spectrometry (EIMS). The synthesized compounds were screened for in vitro antibacterial, antienzymatic and hemolytic activities using standard procedures.Results: All the synthesized compounds showed moderate to high activity against Gram-positive and Gram-negative bacterial strains. The molecules 5g and 5j exhibited good inhibition of α-glucosidase enzyme with half-maximal inhibitory concentration (IC50) of 59.53 ± 0.01 and 55.31 ± 0.01 μmoles/L, respectively, relative to acarbose with IC50 of 38.25 ± 0.12 μmoles/L. All the compounds exhibited cytotoxicity levels ranging from 27.20 ± 0.24 to 5.20 ± 0.41 %, relative to Triton X-100.Conclusion: Compound 5f is the most potent antibacterial while 5j is the best α-glucosidase inhibitor; 5e showed the least cytotoxicity.Keywords: 2,3-Dimethylaniline, Antibacterial activity, Anti-enzymatic activity, α-Glucosidase inhibitor, Hemolytic activity, Sulfonamide

Validated RP-HPLC method for the simultaneous determination of glucosamine sulphate and curcumin in cream formulation: A novel stability-indicating study

Purpose: To develop and validate a stability-indicating reverse phase-high performance liquid chromatography (RP-HPLC) method for the simultaneous determination of glucosamine sulphate (GS) and curcumin (Cur) in drug solution and formulation.Methods: The optimized chromatographic conditions were achieved by passing various compositions of mobile phases over  different reverse phase chromatographic columns. Various validation parameters, including linearity, range, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, specificity and system suitability were performed and evaluated. Stability studies under stressed conditions were done to evaluate the effects of acid, alkali, oxidation, heat and degradation by UV light.Results: The validated method was linear over the concentration range of 0.094 to 1.5 mg/mL for GS and 0.125 to 1.5 mg/mL for Cur, with a correlation coefficient > 0.999. The Intra and inter-day precision were 1.9 % for GS and 0.5 % for Cur, while accuracy was 96 and 102 % for GS and Cur, respectively. Stability studies showed that GS was highly sensitive to acid, alkali and oxidation and less sensitive to heat and UV. Cur was stable against acid, heat and oxidation but sensitive to alkali and UV.Conclusion: The developed and validated method was precise and accurate for both GS and Cur and can potentially be utilized for their identification and quantification at industrial, research and quality control laboratories

Porous and highly responsive polymeric fabricated nanometrices for solubility enhancement of acyclovir; characterization and toxicological evaluation

Solubility is one of the major factors which affects several therapeutic mioeties in terms of their therapeutic efficacy. In the current study, we presented a porous and amorphous nanometrices system for the enhancement of the solubility of acyclovir. The polymeric network was fabricated by crosslinking polyethylene glycol-6000, polycaprolactone, and β-cyclodextrin with methacrylic acid by optimizing free radical polymerization technique using methylene bisacrylamide as a crosslinking agent. The formulated nanometrices were then characterized by zetasizer, FTIR, PXRD, Scanning electron microscopy, Thermogravimetric analysis, swelling, sol-gel fraction, drug loading, stability, solubility, and in-vitro dissolution analysis. Since the formulated system has to be administered orally, therefore to determine the in-vivo biocompatibility, nanometrices were administered orally to experimental animals. SEM images provided a rough and porous structure while PXRD showed an amorphous diffractogram of the unloaded and loaded nanometrices. Moreover, the particle size of the optimum loaded formulation was 25 nm higher than unloaded nanometrices due to the repulsion of the loaded drug. A significant loading of the drug with enhanced solubility and dissolution profiles was observed for the poorly soluble drug. The dissolution profile was quite satisfactory as compared to the marketed brand of drug which depicted that the solubility of the drug has been enhanced. Toxicity study conducted on rabbits confirmed the biocompatibility of the nanometrices. The systematic method of preparation, enhanced solubility and high dissolution profile of the formulated nanometrices may be proved as a promising technique to enhance the solubility of poorly aqueous soluble therapeutic agents

Evaluation of Biological Activities of Chemically Synthesized Silver Nanoparticles

Silver nanoparticles were synthesized by the earlier reported methods. The synthesized nanoparticles were characterized using ultraviolet-visible spectrophotometry (UV/Vis), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), and X-ray powder diffraction (XRD). The synthesized materials were also evaluated for their antibacterial activity against Gram positive and Gram negative bacterial strains. TEM micrograph showed the spherical morphology of AgNPs with size range of 40–60 nm. The synthesized nanoparticles showed a strong antimicrobial activity and their effect depends upon bacterial strain as AgNPs exhibited greater inhibition zone for Pseudomonas aeruginosa (19.1 mm) followed by Staphylococcus aureus (14.8 mm) and S. pyogenes (13.6 mm) while the least activity was observed for Salmonella typhi (12.5 mm) at concentration of 5 µg/disc. The minimum inhibitory concentration (MIC) of AgNPs against S. aureus was 2.5 µg/disc and less than 2.5 µg/disc for P. aeruginosa. These results suggested that AgNPs can be used as an effective antiseptic agent for infectious control in medical field

Development of protein rich pregelatinized whole grain cereal bar enriched with nontraditional ingredient: Nutritional, phytochemical, textural, and sensory characterization

This study was aimed to use extrusion cooking as a pretreatment for non-conventional seeds (Indian horse chestnut flour) to blend them with whole grain flours (whole wheat flour, whole barley flour, and whole corn flour) for the development of a pregelatinized cereal bar (PCB). In this study, date paste (7.5–17.5%) and walnut grits (2.5–12.5%) were incorporated at varying levels to prepare PCB. The PCB was evaluated for its nutritional, color, textural (both three-point bending test and TPA), antioxidant activity, and sensory attributes. The flexural modulus, rupture stress, and fracture strain of PCB increased with the incorporation of a higher proportion of date paste. The protein and fiber content in PCB increased from 7.74 to 9.13% and 4.81 to 5.59% with the incorporation of walnut grits and date paste, respectively. The DPPH, total phenolic content, and water activity of PCB were determined, which progressively enhanced with increased levels of walnut grits and date paste. The correlation between sensory attributes and instrumental texture on PCB was also investigated. The correlation results showed a significant (p < 0.05) positive correlation between texture analysis and sensory hardness, springiness, adhesiveness, and negatively correlated to instrumental and sensory cohesiveness. For sensorial attributes, all PCB samples presented average scores of 7/10 and 4/5 for buying intention. Therefore, whole grain extrudates, date paste, and walnut grits can be efficiently used to develop PCB with improved nutritional, nutraceutical, and economic values

Sustainable adsorption method for the remediation of malachite green dye using nutraceutical industrial fenugreek seed spent

Nutraceutical industrial fenugreek seed spent (NIFGS), a relatively low-cost material abundantly available with nearly negligible toxicity for the bioremediation of malachite green (MG) dye from aqueous media, is reported. Studies on the various parameters affecting the adsorption capacity of NIFGS were carried out to evaluate the kinetics and the equilibrium thermodynamics. All the experiments were designed at about pH 7. The adsorption isotherm model proposed by Langmuir fits better than the Freundlich isotherm model. Kinetic study data confirms the viability of pseudo-second-order model. Calculated thermodynamic factors suggest that the adsorption phenomenon is endothermic, almost instantaneous, and physical in nature

Factors affecting recruitment and retention of community health workers in a newborn care intervention in Bangladesh

<p>Abstract</p> <p>Background</p> <p>Well-trained and highly motivated community health workers (CHWs) are critical for delivery of many community-based newborn care interventions. High rates of CHW attrition undermine programme effectiveness and potential for implementation at scale. We investigated reasons for high rates of CHW attrition in Sylhet District in north-eastern Bangladesh.</p> <p>Methods</p> <p>Sixty-nine semi-structured questionnaires were administered to CHWs currently working with the project, as well as to those who had left. Process documentation was also carried out to identify project strengths and weaknesses, which included in-depth interviews, focus group discussions, review of project records (i.e. recruitment and resignation), and informal discussion with key project personnel.</p> <p>Results</p> <p>Motivation for becoming a CHW appeared to stem primarily from the desire for self-development, to improve community health, and for utilization of free time. The most common factors cited for continuing as a CHW were financial incentive, feeling needed by the community, and the value of the CHW position in securing future career advancement. Factors contributing to attrition included heavy workload, night visits, working outside of one's home area, familial opposition and dissatisfaction with pay.</p> <p>Conclusions</p> <p>The framework presented illustrates the decision making process women go through when deciding to become, or continue as, a CHW. Factors such as job satisfaction, community valuation of CHW work, and fulfilment of pre-hire expectations all need to be addressed systematically by programs to reduce rates of CHW attrition.</p