scholarly journals The Relative Role of Toxins A and B in the Virulence of Clotridioides difficile

2020 ◽  
Vol 10 (1) ◽  
pp. 96
Author(s):  
Andrew M. Skinner ◽  
S. Tyler Phillips ◽  
Michelle M. Merrigan ◽  
Kevin J. O’Leary ◽  
Susan P. Sambol ◽  
...  
Keyword(s):  
Animal Studies ◽  
Specific Treatment ◽  
Restriction Endonuclease Analysis ◽  
Natural Occurrence ◽  
Relative Role ◽  
Intestinal Epithelial ◽  
Large Molecular Weight ◽  
Stool Samples ◽  
Serious Disease ◽  
Isogenic Mutants

Most pathogenic strains of C. difficile possess two large molecular weight single unit toxins with four similar functional domains. The toxins disrupt the actin cytoskeleton of intestinal epithelial cells leading to loss of tight junctions, which ultimately manifests as diarrhea in the host. While initial studies of purified toxins in animal models pointed to toxin A (TcdA) as the main virulence factor, animal studies using isogenic mutants demonstrated that toxin B (TcdB) alone was sufficient to cause disease. In addition, the natural occurrence of TcdA−/TcdB+ (TcdA−/B+)mutant strains was shown to be responsible for cases of C. difficile infection (CDI) with symptoms identical to CDI caused by fully toxigenic (A+/B+) strains. Identification of these cases was delayed during the period when clinical laboratories were using immunoassays that only detected TcdA (toxA EIA). Our hospital laboratory at the time performed culture as well as toxA EIA on patient stool samples. A total of 1.6% (23/1436) of all clinical isolates recovered over a 2.5-year period were TcdA−/B+ variants, the majority of which belonged to the restriction endonuclease analysis (REA) group CF and toxinotype VIII. Despite reports of serious disease due to TcdA−/B+ CF strains, these infections were typically mild, often not requiring specific treatment. While TcdB alone may be sufficient to cause disease, clinical evidence suggests that both toxins have a role in disease.

Proposal of new clinical diagnostic criteria for POEMS syndrome

2018 ◽  
Vol 90 (2) ◽  
pp. 133-137 ◽  
Author(s):  
Tomoki Suichi ◽  
Sonoko Misawa ◽  
Yasunori Sato ◽  
Minako Beppu ◽  
Emiko Sakaida ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Plasma Cell ◽  
Characteristic Curve ◽  
Specific Treatment ◽  
Poems Syndrome ◽  
Bone Lesions ◽  
Standard Group ◽  
Skin Changes ◽  
Immunoglobulin Light Chain Amyloidosis ◽  
Serious Disease

ObjectiveTo propose the optimal diagnostic criteria for polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome using appropriate statistical methods and disease controls.MethodsThis retrospective cohort study included 104 consecutive patients with suspected POEMS syndrome, among whom a gold standard group of 60 patients with definitive POEMS syndrome diagnosis were followed for at least 12 months to strictly exclude other disorders mimicking POEMS syndrome and to confirm response to POEMS syndrome-specific treatment. Thirty patients with chronic inflammatory demyelinating polyradiculoneuropathy (demyelinating polyradiculoneuropathy controls) and 30 with multiple myeloma or immunoglobulin light chain amyloidosis (monoclonal plasma cell proliferation controls) were also included. Logistic regression analyses were performed to determine optimal combination of clinical and laboratory abnormalities, characteristic of POEMS syndrome.ResultsThe diagnostic criteria were statistically defined as the presence of the three major criteria (polyneuropathy (typically demyelinating), monoclonal plasma cell proliferative disorder and elevated vascular endothelial growth factor) and at least two of the four minor criteria (oedema/effusion, skin changes, organomegaly and sclerotic bone lesions), based on best performance by area under the receiver operating characteristic curve analyses. The sensitivity and specificity were 100% and 100%, respectively; the diagnostic accuracy of the proposed criteria was equivalent to somewhat complicated previous criteria.ConclusionsThe statistically defined, simple diagnostic criteria for POEMS syndrome could accelerate early diagnosis and treatment, thereby contribute to better outcome in patients with this serious disease. Prospective larger studies are required to confirm the validity.

scholarly journals Preliminary Evidence for an Association Between the Composition of the Gut Microbiome and Cognitive Function in Neurologically Healthy Older Adults

2017 ◽  
Vol 23 (8) ◽  
pp. 700-705 ◽  
Author(s):  
Lisa Manderino ◽  
Ian Carroll ◽  
M. Andrea Azcarate-Peril ◽  
Amber Rochette ◽  
Leslie Heinberg ◽  
...  
Keyword(s):  
Older Adults ◽  
Gut Microbiome ◽  
Test Performance ◽  
Animal Studies ◽  
Preliminary Evidence ◽  
Community Dwelling ◽  
Cognitive Test ◽  
Healthy Older Adults ◽  
Stool Samples ◽  
Cognitive Test Performance

AbstractObjectives: Dysbiosis of the gut microbiome is implicated in numerous human health conditions. Animal studies have linked microbiome disruption to changes in cognitive functioning, although no study has examined this possibility in neurologically healthy older adults. Methods: Participants were 43 community-dwelling older adults (50–85 years) that completed a brief cognitive test battery and provided stool samples for gut microbiome sequencing. Participants performing≥1 SD below normative performance on two or more tests were compared to persons with one or fewer impaired scores. Results: Mann Whitney U tests revealed different distributions of Bacteroidetes (p=.01), Firmicutes (p=.02), Proteobacteria (p=.04), and Verrucomicrobia (p=.003) between Intact and Impaired groups. These phyla were significantly correlated with cognitive test performances, particularly Verrucomicrobia and attention/executive function measures. Conclusions: The current findings suggest that composition of the gut microbiome is associated with cognitive test performance in neurologically healthy older adults. Future studies are needed to confirm these findings and explore possible mechanisms. (JINS, 2017, 23, 700–705)

scholarly journals Intestinal parasites in school food handlers in the city of Uberlândia, Minas Gerais, Brazil

1995 ◽  
Vol 37 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Julia Maria Costa-Cruz ◽  
Margareth Leitão Gennari Cardoso ◽  
Daldy Endo Marques
Keyword(s):  
Giardia Lamblia ◽  
Intestinal Parasites ◽  
Specific Treatment ◽  
Strongyloides Stercoralis ◽  
Minas Gerais ◽  
Food Handlers ◽  
School Food ◽  
Public Elementary Schools ◽  
Stool Samples ◽  
The City

In order to verify the presence of intestinal parasites in food handlers, stool samples were collected from 104 cooks and their helpers that were working in food preparation in 20 public elementary schools, in various areas of the city of Uberlândia, Minas Gerais, Brazil. The samples were collected during the months of November and December, 1988, in plastic flasks containing a 10% formaldehyde solution and processed by the Hoffmann, Pons & Janer method. The sediment was examined using triplicate slides. All individuals were females aged between 24 to 69 years. Intestinal parasites were found in 85.0% of the studied schools and 47.1% of the studied food handlers (cooks and helpers) were found to be positive. Among the 49 infected food handlers, 32 (65.3%) carried a single parasite and 17 (34.7%) carried two parasites. The following intestinal parasites were found: Giardia lamblia (21.1%), Entamoeba coli (21.1%), hookworms (9.6%), Ascaris lumbricoides (5.8%), Entamoeba histolytica (2.9%), Hymenolepis nana (1.9%), Strongyloides stercoralis (1.0%). These data emphasize the need for a rigid semi-annual control in all school food handlers, including diagnosis, specific treatment and orientation about the mechanisms of transmission of the intestinal parasites.

DOZ047.108: Utilizing dynamic CT imaging to map tissue regeneration in a porcine model of esophageal loss

2019 ◽  
Vol 32 (Supplement_1) ◽  
Author(s):  
T Jensen ◽  
I Sharma ◽  
W Fodor ◽  
S Sundaram ◽  
T Roffidal ◽  
...  
Keyword(s):  
Animal Studies ◽  
Specific Treatment ◽  
Regenerative Process ◽  
Patient Specific ◽  
Complication Rates ◽  
Tubular Scaffold ◽  
Fully Connected ◽  
Very High ◽  
Correct Structure

Abstract Esophageal atresia (EA) is a congenital defect in which the esophagus is not fully connected. Current treatments to bring together long gaps between the esophagus have very high complication rates and the replacement tissue does not possess the correct structure or physiologic properties. Tissue engineering and regenerative medicine have been suggested as a new patient-specific treatment for EA utilizing the patient's own cells and a tubular scaffold. Our group recently published on the successful regeneration of an esophagus using a retrievable scaffold seeded with amniotic derived MSCsFurther evaluation with dynamic computed tomography has suggested that the regenerative process entails ingrowth of native esophageal cells from both proximal and distal ends including robust vascular ingrowth. This confirms our gene expression findings and lends support to our hypothesis that the regenerative process is driven by vascular ingrowth. The role of the cells seeded on esophageal scaffolds and how this affects the regenerative process is the focus of current investigation with animal studies that are ongoing.

scholarly journals Delivery Mode Affects Intestinal Microbial Composition and the Development of Intestinal Epithelial Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Linzheng Lyu ◽  
Xiaohong Zhou ◽  
Meng Zhang ◽  
Li Liu ◽  
Haiyue Niu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Vaginal Delivery ◽  
Intestinal Epithelial Cells ◽  
Delivery Mode ◽  
Apparent Difference ◽  
Intestinal Epithelial ◽  
Microbial Composition ◽  
Delivery Modes ◽  
Rat Pups ◽  
Stool Samples

BackgroundThe infant’s intestine contains diverse microbiota, which play an important role in an infant’s health.ObjectiveThis study aimed to analyze the different intestinal microbiota and their function in two delivery modes [vaginal delivery and cesarean section (C-section)] and to investigate the proprieties of bacteria associated with vaginal delivery on the development of intestinal epithelial cells in rat pups.Materials and MethodsWe evaluated the intestinal microbial diversity of the stool samples of 51 infants of subjects who underwent vaginal delivery and C-section by sequencing the V4 regions of the 16S rRNA gene and predicted the function of the microbiotas. The infant stool microbiota in the vaginal delivery group was associated with the digestive system and cell growth and death, whereas that of the C-section group was associated with membrane transport. Then, we isolated the strains based on function prediction.ResultsA total of 95 strains were isolated in the vaginal delivery group. Bifidobacterium bifidum FL-228.1 (FL-228.1) was screened and selected owing to its good surface hydrophobicity, bacterial survivability in the simulated gastrointestinal condition and adhesion ability to the IEC-6 cell line as well as owing to the development of intestinal epithelial cells. Furthermore, in vivo experiments revealed that FL-228.1 exhibited favorable effects on the development of intestinal epithelial cells in rat pups.ConclusionThe results of this study indicate an apparent difference in the bacterial composition of the stool samples collected from infants of the two delivery modes. By analyzing and screening the bacteria in infant stool samples, we found that one strain, i.e., B bifidum FL-228.1, exhibited favorable effects on the development of intestinal epithelial cells.

scholarly journals Evidence Implicating Non-Dioxin-Like Congeners as the Key Mediators of Polychlorinated Biphenyl (PCB) Developmental Neurotoxicity

2020 ◽  
Vol 21 (3) ◽  
pp. 1013 ◽  
Author(s):  
Carolyn Klocke ◽  
Pamela J. Lein
Keyword(s):  
Animal Studies ◽  
Polychlorinated Biphenyl ◽  
Significant Proportion ◽  
Significant Risk ◽  
Epidemiological Studies ◽  
Experimental Models ◽  
Developmental Neurotoxicity ◽  
Relative Role ◽  
Neurodevelopmental Outcomes ◽  
Critical Data

Despite being banned from production for decades, polychlorinated biphenyls (PCBs) continue to pose a significant risk to human health. This is due to not only the continued release of legacy PCBs from PCB-containing equipment and materials manufactured prior to the ban on PCB production, but also the inadvertent production of PCBs as byproducts of contemporary pigment and dye production. Evidence from human and animal studies clearly identifies developmental neurotoxicity as a primary endpoint of concern associated with PCB exposures. However, the relative role(s) of specific PCB congeners in mediating the adverse effects of PCBs on the developing nervous system, and the mechanism(s) by which PCBs disrupt typical neurodevelopment remain outstanding questions. New questions are also emerging regarding the potential developmental neurotoxicity of lower chlorinated PCBs that were not present in the legacy commercial PCB mixtures, but constitute a significant proportion of contemporary human PCB exposures. Here, we review behavioral and mechanistic data obtained from experimental models as well as recent epidemiological studies that suggest the non-dioxin-like (NDL) PCBs are primarily responsible for the developmental neurotoxicity associated with PCBs. We also discuss emerging data demonstrating the potential for non-legacy, lower chlorinated PCBs to cause adverse neurodevelopmental outcomes. Molecular targets, the relevance of PCB interactions with these targets to neurodevelopmental disorders, and critical data gaps are addressed as well.

scholarly journals 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology

2020 ◽  
Vol 22 (1) ◽  
pp. 181
Author(s):  
Massimo E. Maffei
Keyword(s):  
Animal Studies ◽  
Tryptophan Hydroxylase ◽  
Metabolic Diseases ◽  
Physiological Role ◽  
Molecular Engineering ◽  
Natural Occurrence ◽  
Treatment Of Depression ◽  
Analysis And Synthesis ◽  
Natural Component

L-5-hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed to melatonin (N-acetyl-5-methoxytryptamine). 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis. In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials. The physiological role of 5-HTP in the treatment of depression, anxiety, panic, sleep disorders, obesity, myoclonus and serotonin syndrome are also discussed. 5-HTP toxicity and the occurrence of toxic impurities present in tryptophan and 5-HTP preparations are also discussed.

scholarly journals Clonal structure of invasiveStreptococcus pyogenesin Northern Scotland

1995 ◽  
Vol 115 (2) ◽  
pp. 231-241 ◽  
Author(s):  
M. Upton ◽  
P. E. Carter ◽  
M. Morgana ◽  
G. F. Edwards ◽  
T. H. Pennington
Keyword(s):  
Severe Infection ◽  
Restriction Endonuclease Analysis ◽  
Molecular Techniques ◽  
Clonal Structure ◽  
The Usa ◽  
Group A ◽  
Polymerase Chain ◽  
Serious Disease ◽  
Type 3

SummaryWe have used molecular techniques to characterize 51 group A streptococci from Scotland and 17 ‘serious disease’ isolates from other countries, in order to establish the clonal structure of invasiveStreptococcus pyogenesstrains circulating between 1986 and 1993. Strains were grouped by restriction endonuclease analysis, pulsed field gel electrophoresis and ribotyping patterns, and were examined for the presence of alleles of thespeAgene by polymerase chain reaction and DNA sequence analysis. Serious and fatal infections in Scotland were caused by several clones. One clone (9 of 51 strains) was M type 1 and possessed thespeAgene allele 2. This was the clone previously identified as causing severe infection in the USA. Another clone (5 of 51 strains) was M type 3 and hadspeAgene allele 3. In view of the clear association of more than one clone with severe, invasive and fatal infections, horizontal gene exchange between genotypes merits further investigation.

scholarly journals Candida albicanswhite and opaque cells exhibit distinct spectra of organ colonization in mouse models of infection

2018 ◽  
Author(s):  
Julie Takagi ◽  
Sheena D. Singh-Babak ◽  
Matthew B. Lohse ◽  
Chiraj K. Dalal ◽  
Alexander D. Johnson
Keyword(s):  
Candida Albicans ◽  
Animal Studies ◽  
Murine Models ◽  
Gi Tract ◽  
Internal Organs ◽  
Mucosal Surfaces ◽  
Default State ◽  
Serious Disease ◽  
First Time ◽  
Organ Colonization

AbstractCandida albicans, a species of fungi, can thrive in diverse niches of its mammalian hosts; it is a normal resident of the GI tract and mucosal surfaces but it can also enter the bloodstream and colonize internal organs causing serious disease. The ability ofC. albicansto thrive in these different host environments has been attributed, at least in part, to its ability to assume different morphological forms. In this work, we examine one such morphological change known as white-opaque switching. White cells are the default state ofC. albicans, and most animal studies have been carried out exclusively with white cells. Here, we compared the proliferation of white and opaque cells in two murine models of infection and also monitored, using specially constructed strains, switching between the two states in the host. We found that white cells outcompeted opaque cells in many niches; however, we show for the first time that in some organs (specifically, the heart and spleen), opaque cells competed favorably with white cells and, when injected on their own, could colonize these organs. In environments where the introduced white cells outcompeted the introduced opaque cells, we observed high rates of opaque-to-white switching. We did not observe white-to-opaque switching in any of the niches we examined.

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