Mannose-rich guar gum nanoparticles as a novel therapeutic drug against inflammatory diseases

The potential to deliver nanoparticles, like polymer-based nanoparticles that can be enriched with functional groups to ensure entry into cells, directly into targeted cells is important for the therapy of inflammatory diseases. Plant-derived nanoparticles, with inherent anti-inflammatory activity and modified to allow receptor-mediated uptake, can be used as effective therapy with minimal side effects. The particle used in this study is an edible polysaccharide, derived from Cyamopsis tetragonoloba, with a galactomannan component. The particle was made mannose-rich to increase specificity towards cells expressing mannose receptors, and initially tagged with rhodamine isothiocyanate to trace its path. This study aimed to determine the therapeutic effect of the guar gum nanoparticle (GN) in vitro and in vivo in inflammatory diseases. In vitro studies on RAW 264.7 cells showed successful uptake of the nanoparticle, in a short duration of time, via their mannose receptors. Nitric oxide and MTS assays showed anti-inflammatory effects of GN. In vivo mouse model of thioglycollate-induced peritonitis showed significant decrease in inflammation, indicating its anti-inflammatory effect, and increase in clonogenic potential, indicating its regenerative potential, on intraperitoneal administration of GN. The results reflect the potential of the nanoparticle in cellular trafficking, site- specific drug delivery and bioimaging applications

Antimicrobial Susceptibility of Enteric Gram Negative Facultative Anaerobe Bacilli in Aerobic versus Anaerobic Conditions

Citation: DeMars, Z., Biswas, S., Amachawadi, R. G., Renter, D. G., & Volkova, V. V. (2016). Antimicrobial Susceptibility of Enteric Gram Negative Facultative Anaerobe Bacilli in Aerobic versus Anaerobic Conditions. Plos One, 11(5). doi:10.1371/journal.pone.0155599Antimicrobial treatments result in the host's enteric bacteria being exposed to the antimicrobials. Pharmacodynamic models can describe how this exposure affects the enteric bacteria and their antimicrobial resistance. The models utilize measurements of bacterial antimicrobial susceptibility traditionally obtained in vitro in aerobic conditions. However, in vivo enteric bacteria are exposed to antimicrobials in anaerobic conditions of the lower intestine. Some of enteric bacteria of food animals are potential foodborne pathogens, e.g., Gram-negative bacilli Escherichia coli and Salmonella enterica. These are facultative anaerobes; their physiology and growth rates change in anaerobic conditions. We hypothesized that their antimicrobial susceptibility also changes, and evaluated differences in the susceptibility in aerobic vs. anaerobic conditions of generic E. coli and Salmonella enterica of diverse serovars isolated from cattle feces. Susceptibility of an isolate was evaluated as its minimum inhibitory concentration (MIC) measured by E-TestR following 24 hours of adaptation to the conditions on Mueller-Hinton agar, and on a more complex tryptic soy agar with 5% sheep blood (BAP) media. We considered all major antimicrobial drug classes used in the U.S. to treat cattle: ?-lactams (specifically, ampicillin and ceftriaxone E-Test1 ), aminoglycosides (gentamicin and kanamycin), fluoroquinolones (enrofloxacin), classical macrolides (erythromycin), azalides (azithromycin), sulfanomides (sulfamethoxazole/ trimethoprim), and tetracyclines (tetracycline). Statistical analyses were conducted for the isolates (n?30) interpreted as susceptible to the antimicrobials based on the clinical breakpoint interpretation for human infection. Bacterial susceptibility to every antimicrobial tested was statistically significantly different in anaerobic vs. aerobic conditions on both media, except for no difference in susceptibility to ceftriaxone on BAP agar. A satellite experiment suggested that during first days in anaerobic conditions the susceptibility changes with time. The results demonstrate that assessing effects of antimicrobial treatments on resistance in the host's enteric bacteria that are Gram negative facultative Anaerobe Bacilli requires data on the bacterial antimicrobial susceptibility in the conditions resembling those in the intestine. © 2016 DeMars et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Correction: Global Patterns in Human Mitochondrial DNA and Y-Chromosome Variation Caused by Spatial Instability of the Local Cultural Processes

Because of the widespread phenomenon of patrilocality, it is hypothesized that Y-chromosome variants tend to be more localized geographically than those of mitochondrial DNA ( mtDNA). Empirical evidence confirmatory to this hypothesis was subsequently provided among certain patrilocal and matrilocal groups of Thailand, which conforms to the isolation by distance mode of gene diffusion. However, we expect intuitively that the patterns of genetic variability may not be consistent with the above hypothesis among populations with different social norms governing the institution of marriage, particularly among those that adhere to strict endogamy rules. We test the universality of this hypothesis by analyzing Y-chromosome and mtDNA data in three different sets of Indian populations that follow endogamy rules to varying degrees. Our analysis of the Indian patrilocal and the matrilocal groups is not confirmatory to the sex- specific variation observed among the tribes of Thailand. Our results indicate spatial instability of the impact of different cultural processes on the genetic variability, resulting in the lack of universality of the hypothesized pattern of greater Y-chromosome variation when compared to that of mtDNA among the patrilocal populations

Antibiotic Resistance in Salmonella Typhimurium Isolates Recovered From the Food Chain Through National Antimicrobial Resistance Monitoring System Between 1996 and 2016

Salmonella is a major foodborne pathogen which causes widespread contamination and infection worldwide. Salmonella Typhimurium is one of the leading serovars responsible for human and animal salmonellosis, globally. The increasing rate of antibiotic resistance in Salmonella Typhimurium poses a significant global concern, and an improved understanding of the distribution of antibiotic resistance patterns in Salmonella Typhimurium is essential for choosing the suitable antibiotic for the treatment of infections. To evaluate the roles of animal and human in antibiotic resistance dissemination, this study aims to categorize 11,447 S. Typhimurium strains obtained across the food-chain, including food animals, retail meats and humans for 21 years in the United States by analyzing minimum inhibitory concentrations (MICs) values for 27 antibiotics. Random Forest Algorithm and Hierarchical Clustering statistics were used to group the strains according to their minimum inhibitory concentration values. Classification and Regression Tree analysis was used to identify the best classifier for human- and animal-populations’ isolates. We found the persistent population or multi-drug resistant strains of S. Typhimurium across the four time periods (1996∼2000, 2001∼2005, 2006∼2010, 2011∼2016). Importantly, we also detected that there was more diversity in the MIC patterns among S. Typhimurium strains isolated between 2011 and 2016, which suggests significant emergence of diversified multi-drug resistant strains. The most frequently observed (43%) antibiotic resistance patterns found in S. Typhimurium were tetra-resistant pattern ASSuT (ampicillin, streptomycin, sulfonamides, and tetracycline) and the penta-resistant pattern ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline). Animals (mainly swine and bovine) are the major source for these two frequently found antibiotic resistance patterns. The occurrence of antibiotic resistant strains from humans and chicken is alarming. Strains were mostly susceptible to fluoroquinolones. Together, this study helped in understanding the expansion of dynamics of antibiotic resistance of S. Typhimurium and recommended fluoroquinolones as a possible treatment options against S. Typhimurium infection

Emergence and Dissemination of mcr-Carrying Clinically Relevant Salmonella Typhimurium Monophasic Clone ST34

Antibiotic resistance in bacteria is one of the urgent threats to both public and global health. The Salmonella Typhimurium monophasic sequence type 34 (ST34) clone, with its rapid dissemination and resistance to numerous critical antimicrobials, has raised global concerns. Here, we present an updated overview on the emerging infections caused by mobile colistin resistance (mcr)-carrying colistin-resistant ST34 isolates, covering their global dissemination and virulence-associated efficacy. The higher rates of mcr-1-positive ST34 in children in China highlights the increasing threat caused by this pathogen. Most of the ST34 isolates carrying the mcr-1 gene were isolated from animals and food products, indicating the role of foodborne transmission of mcr-1. The emergence of multidrug resistance genes along with various virulence factors and many heavy metal resistance genes on the chromosome and plasmid from ST34 isolates will challenge available therapeutic options. The presence of the colistin resistance gene (mcr-1, mcr-3, and mcr-5) with the multidrug-resistant phenotype in ST34 has spread across different countries, and most of the mcr-1 genes in ST34 isolates were detected in plasmid type IncHI2 followed by IncI2, and IncX4. Together, mcr-carrying S. Typhimurium ST34 may become a new pandemic clone. The fast detection and active surveillance in community, hospital, animal herds, food products and environment are urgently warranted

Support moléculaire de la résistance aux antibiotiques chez les bactéries intracellulaires

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Role of free radicals in human inflammatory diseases

The role of free radicals can be found in the inflammatory process which is a complex process resulting many human diseases. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. In recent years, there has been a great deal of attention to the field of free radical chemistry. Free radicals such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated by our body by various endogenous systems, exposure to different physiochemical conditions or pathological states. The purpose of the present review is to mention the role of free radical formation in the most common inflammatory processes in animals. Continued oxidative stress can lead to chronic inflammation, which in turn could mediate the most chronic diseases including cancer, diabetes, cardiovascular, neurological, and pulmonary diseases. ROS and RNS are well recognized for playing role as deleterious species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. The detrimental effect of free radicals causing health damages is termed oxidative stress and nitrosative stress. Overproduction of ROS results in oxidative stress, a deleterious process that can damage cell structures, including lipids, proteins, and DNA

Molecular Characterization of Resistance to Macrolides in Bartonella henselae

We selected in vitro erythromycin-resistant strains of Bartonella henselae. The mutants obtained had point mutations in domain V of 23S rRNA and/or in ribosomal protein L4. One lymph node of a patient with cat-scratch disease had such a mutation in 23S rRNA, suggesting that natural resistant strains may infect humans

Changing Paradigms in Antibiotic Resistance in Salmonella Species with Focus on Fluoroquinolone Resistance: A 5-Year Retrospective Study of Enteric Fever in a Tertiary Care Hospital in Kolkata, India

Enteric fever, a potentially fatal multisystem disease that is caused by Salmonella enterica serovar Typhi and Paratyphi, poses a significant risk in low- and middle-income countries. A retrospective study to understand the prevalence and evolving patterns of antibiotic resistance in Salmonella Typhi and Paratyphi was undertaken from June 2017 to June 2022. A total of 4051 blood samples were collected from patients attending inpatient and outpatient departments of the School of Tropical Medicine (Kolkata, India) hospital. Blood samples were cultured, and culture positive samples were further processed for identification using conventional and automated systems. Antibiotic susceptibility test was performed using both the Kirby-Bauer disc diffusion method and VITEK2 (bioMerieux). Forty-five (1.1%) Salmonella species were isolated among the number of total (n = 4051) samples that were tested. Out of the 45 Salmonella isolates, 35 were Salmonella Typhi (77.77%) and 10 were Salmonella Paratyphi A (22.23%). We found pronounced fluoroquinolone resistance of 100% in the recent years (2019–2022) in both of the S. Typhi and S. Paratyphi A isolates. We found that 1 Salmonella Typhi and 2 Salmonella Paratyphi A isolates were resistant against multiple antibiotics (cefixime, ceftriaxone, ciprofloxacin and nalidixic acid), and 1 multidrug-resistant (MDR) Salmonella Paratyphi A isolate was found in a recent study year (2020) and it showed resistance against different classes of antibiotics (cephalosporins, fluoroquinolones and carbapenems). There was no resistance that was detected to the 3rd generation cephalosporins in the final years of the study. The emergence of Salmonella isolates that are resistant to multiple antibiotics poses a serious health problem. The antimicrobial resistance patterns that were detected in the study thus warrant further studies to understand the antibiotic susceptibility and resistance pattern of Salmonella against the major classes of antibiotics